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JOURNAL FOR

Volume 1 - Issue 1

✓ PATIENT COMPLIANCE

Strategies to enhance Health Outcomes A Patient-Centric Approach to Adherence Pharmacovigilance & New legislation The role of patient compliance Factors that Influence Patient Compliance for Observational Studies Are all MDS created equal? The common myths of compliance laid bare

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Contents JOURNAL FOR

PATIENT COMPLIANCE

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Foreword

Patient Story

Strategies to enhance Health Outcomes

DIRECTORS Mark A. Barker Martin Wright

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PUBLISHER Clive Baigent MANAGING EDITOR Mark A. Barker

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EDITORIAL COORDINATOR Susan James 10

Will FDAAA (REMS) Bring Therapy Compliance to the Next Level? The Administration Amendments Act of 2007 (FDAAA) provides a new statutory framework and authority for FDA to require Risk Evaluation and Mitigation Strategies (REMS) for drugs and biologics. Specifically, FDAAA permits FDA to require applicants for a New Drug Application, Biologics License Application, Abbreviated New Drug Application or a supplement thereof to submit a proposed REMS as part of the application prior to approval, if the Agency determines that it is “necessary to ensure that the benefits of the drug outweigh the risks of the drug”. The EMA demands similar strategies. All this underlines the importance of patient safety and patient protection against the expected and unexpected during drug therapy. By Peter van Iperen – Member of JPC Editorial Advisory Board

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Pharmacovigilance and New Legislation: The Role of Patient Compliance With the globalisation of the pharmaceutical market, the current system of EU pharmacovigilance is changing. How is this affecting pharma and patients? By Konstantina Gogi of BIOAXIS Healthcare

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Patient Compliance, ePRO and the Role of the Care-giver Sponsor companies are increasingly required to employ methods for patient reported outcomes (PROs) that ensure timely, accurate and attributable data collection, as well as to improve patient compliance. In many drug trials, electronic patient reported outcome (ePRO) systems, particularly electronic diaries (eDiaries), have been shown to be an effective and superior method of driving patient compliance when compared to paper-based methods. By Rohini Beavon, PhD, Director of R Beavon Solutions Limited and Kai Langel of CRF Health

EDITORIAL ASSISTANTS Nick Love, Kevin Cross, Lanny McEnzie DESIGN DIRECTOR Ricky Elizabeth RESEARCH & CIRCULATION MANAGER Dorothy Brooks BUSINESS DEVELOPMENT Anthony Stewart Delano Johnson Zoya Berkley ADMINISTRATOR Barbara Lasco FRONT COVER © iStockphoto PUBLISHED BY Pharma Publications Building K, Unit 104 Tower Bridge Business Complex, 100 Clements Road, London, SE16 4DG, UK Tel: +44 0207 2375685 Fax: +44 0207 3947415 Email: info@pharmapubs.com Journal For Patient Compliance – Strategies to enhance Health Outcomes. ISSN 2045-9823 is published quarterly by PHARMAPUBS.

The opinions and views expressed by the authors in this magazine are not necessarily those of the Editor or the Publisher. Please note that although care is taken in preparation of this publication, the Editor and the Publisher are not responsible for opinions, views and inaccuracies in the articles. Great care is taken with regards to artwork supplied, the Publisher cannot be held responsible for any loss or damage incurred. This publication is protected by copyright.

Choosing Not to Take Medication: How Patients Can Help Other Patients Get Better Brittney Wilson, a registered nurse, and Michael Wong of hcCatalyst discuss this topic. The most common opinion of patients who don’t take their medications is that they’re forgetful and need reminders. This may be true of some people, but many or perhaps even most actually choose not to take their medication.

2011 PHARMA PUBLICATIONS www.JforPC.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 1


Contents Regulatory & Marketplace 16

Medication Management and Health Outcomes The manufacture of pharmaceuticals is well regulated from inception to production, yet the misuse of these same products causes hundreds of billions of dollars of damage on an annual basis, with immeasurable impact on the lives of the patients and their families. There is no other product category with such wide use where similar performance is tolerated. Whether it’s the food, appliance, automotive or airline industry, safety issues are identified and then rectified. How can the regular mismanagement of pharmaceuticals not demand the same scrutiny as these other categories? Walter Berghahn, Executive Director of the Healthcare Compliance Packaging Council, puts his arguments forward.

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The Patient-Centered Medical Home and Medication Management The basic concept of medical home is the primary-care provider taking responsibility for a patient’s health and coordinated care — with the provider being compensated for his efforts. Edwina Rogers of the Patient-Centered Primary Care Collaborative explains how pharmacists connect to the process, and its importance to the success of medication management.

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The Community Pharmacy’s Role in Patient Adherence According to the World Health Organization, between 30 and 50 per cent of medicines prescribed for chronic diseases are not taken as directed. Statistics for medicines that address acute diseases are better, but not by much. Non-adherence costs the pharma industry billions every year and leads to both disease escalation and deaths. But pharmacists can help. Andrew Tolve discusses how working with pharmacies and helping to establish frontline services, pharma companies can help patients, stakeholders, and their bottom lines. 280 Billion Reasons why We Can No Longer Afford to Ignore Patient Adherence Dyan Bryson of Inspired Health Strategies reviews why we can no longer afford to ignore patient adherence, and concludes that as population demographics change there will be opportunity to support an older, chronically ill patient. There is the opportunity to speak to patients in ways that are culturally relevant, to help patients manage barriers to managing their health. The only way we will recognise this is to keep our focus on the needs of the patient, then the bottom line will follow.

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Behaviour Programmes 28 A Patient-Centric Approach to Adherence Pharmaceutical marketers face the complex undertaking of maintaining patient adherence with Rx medications — especially when a chronic disease plagues the patient. Such patients are constantly exposed to a deluge of information from every healthcare source. In addition, many such diseases present themselves later in life, after lifestyle routines have been established and are exceedingly tough to change. Not only are these patients told to take their medications; they are expected to maintain a treatment/lifestyle regimen that presents a staggering array of physical and emotional barriers to adherence. Jay H. Bolling of Roska Healthcare Advertising explains that, for an adherence programme to be successful, it must incorporate a sensibility toward patients’ potential state of denial/apathy via direct-to-patient (DTP) relationship marketing. 32 Compliance: the Greatest Enemy of Cure Thom de Bruijn, expert in compliance and designer of the Pillkey® Medication Manager writes on Compliance: the Greatest Enemy of Cure. Compliance or adherence is one of the biggest problems in healthcare. With so many researches, discussions, meetings and articles about this issue, it needs a new, fine, intelligent and fresh perspective to add something. Thom examines the issues further in this article. Clinical Trials 34 Addressing the Patient Factor in ePRO to Improve Compliance Patient-Reported Outcomes (PROs) are commonly used by biopharmaceutical companies to support regulatory filings, formulary submissions and product marketing. Sponsors of PRO research have learned that patient compliance is dramatically improved when data is collected electronically from patients rather than by paper. Electronic PatientReported-Outcomes (ePRO) compliance rates, however, can also be improved if sponsors understand the reasons for noncompliance and patient preferences for PRO data collection. Jennifer Ross and Hannah O’Gorman of Almac Clinical Technologies review the literature on patient compliance relating to ePRO, and summarise recent research conducted with patients to provide a broad picture of how sponsors can improve patient compliance during trials involving PRO.

Volume 1 - Issue 1


Contents 38

Factors that Influence Patient Compliance for Observational Studies Observational studies all begin with a blueprint. These initial plans invariably include clear objectives, liberal patient eligibility criteria and easily quantifiable endpoints. With proper discipline, the resulting study design will feature a simple method for collecting data, as well as an effective approach for ensuring that the critical patient-physician/ medical care interface reflects the “real world” of postapproval clinical care. The objective of this article by Dr Ronald E. Weishaar of PharmaNet’s Phase IV Development Group, is to identify the most important elements of observational studies that influence patient compliance, not in terms of adherence to a prescribed diet or treatment, but whether the patient remains an active participant in the project.

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Using Mobile Phone-Based Technologies for Improved Patient Recruitment, Retention, Compliance and Data Reporting in Clinical Trials Patient retention and compliance are critical components in the success of clinical studies. Through a lack of planning, the risk of patient drop-out is extremely high, and will only increase as trials become more complex and lengthy. Mobile phone-based communication technology has been introduced to address these challenges and improve patient retention and compliance, all while complying with regulatory standards. Tim Davis of Exco InTouch discusses the latest advances in mobile phone-based communication technology and demonstrates its benefits for patient retention and compliance through a real-life application.

53 The Role of Qualitative Research in Patient Comprehension Testing For Product Labels and Medication Guides The US Food and Drug Administration (FDA) deems that for a drug or medical device to be considered safe, its labelling needs to provide “adequate directions for use” (Food Drug and Cosmetic Act, 2011). As communications are often directed at patients who use these health products, “adequate directions for use” means directions under which the layman can use a medicine or device safely and for the purposes intended. To fulfil the obligation to provide patients with adequate usage directions, companies often test their product label to ensure that the information provided can be understood by the average patient or consumer. Louis A. Morris, Lauren E. Sandstrom and Paul M. Coplan examines issues with regard to the role of qualitative research in patient comprehension testing. 57 Are all MDSs Created Equal? The Common Myths of Compliance Laid Bare Recent articles in industry ‘bibles’, The Pharmaceutical Journal and British Medical Journal, have highlighted that common misconceptions about MDS endure, even among the country’s senior pharmacy and medical professionals. The myths around MDS are so deeply ingrained, even GANFYD, the GP’s answer to Wikipedia, has got it wrong. As technology continues to progress apace, the creator of the first Britishdesigned monitored dosage system, Protomed’s Norman Niven, brings us up to speed on the truths and myths of MDS. Interview

Drug Delivery, Drug Packaging, Labelling & Dispensing 44

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Creating a Value-Added Packaging Design using Web-Enabled Smart Technology Chris Penfold of Design Cognition looks in detail at the various issues relating to creating a value-added packaging design using web-enabled smart technology. This detailed article asks how new technology is being used in FMCG. Medical Field and Compliance/Adherence issues are explored, as are markets with limited internet access? Other aspects looked at include what we can learn from this anti-counterfeiting approach to aid patient compliance and adherence in emerging markets, and the future of medical packaging.

60 Fighting Back at Counterfeiters Neil Ivey, North American Sales Development Manager at Payne Security, discusses with Mark Barker of Pharma Publications how brand protection solutions can work to protect pharmaceutical companies from counterfeiters. FOLKLORE 62 Uncle Mehmet’s Makat By Nijat Akkaraca

A Tool for Designing and Evaluating Packaging for Healthcare Products Although significant resources are devoted to developing healthcare products that are safe and effective pharmacologically, significantly less effort is devoted to ensuring products perform as intended in the hands of providers and patients. Poor designs result in user confusion and frustration, and have the potential to lead to errors and adverse events. The interaction that occurs between people and healthcare products is an area in need of study. Javier de la Fuente of Factor IDD and Laura Bix at the School of Packaging at Michigan State University introduce the human-package interaction framework, which is an analysis tool to support decision-making while designing and evaluating healthcare products.

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Volume 1 - Issue 1


FOREWORD

Volume 1 - Issue 1

     A Patient-Centric Approach to Adherence Pharmacovigilance & New legislation The role of patient compliance Factors that Influence Patient Compliance for Observational Studies Are all MDS created equal? The common myths of compliance laid bare

www.JforPC.com

J. Rick Turner, PhD Senior Scientific Director, Cardiac Safety Services, Quintiles and Editor-in-Chief, Drug Information Journal

JOURNAL FOR

Strategies to enhance Health Outcomes

Journal For Patient Compliance Strategies to enhance Health Outcomes

New drug development is a lengthy, expensive and complex undertaking, but one that makes an enormous difference to the health and wellbeing of people across the globe; it is a noble pursuit. However, along with biopharmaceutical manufacturing, it is but one component of integrated pharmaceutical medicine: drugs are developed and manufactured to facilitate successful pharmacotherapy. Like drug development and manufacturing, pharmacotherapy is also a multidisciplinary pursuit, involving prescribing physicians, dispensing pharmacists, nursing and other health professionals who administer medicines in in-patient and residential settings, and the individuals who have historically received far too little attention - patients themselves. Fortunately, this situation is changing for the better. One example is that patient advocate groups and patient representatives are being invited to scientific meetings more frequently to provide unique insights. The Journal for Patient Compliance also provides encouraging evidence that the central role of the patient is being considered to a greater extent, and it is a welcome and novel addition to the behavioural pharmacotherapy literature. It can be much more difficult than might naively be assumed to comply with even the simplest medication regimen, e.g., one tablet to be taken once a day. Two immediate potential problems are remembering to take the tablet, and remembering whether or not one has already taken it. Consider the first scenario. Failing to remember to take a day’s medication means that the prescribed dose is not taken, which may impact the effectiveness of the drug. In the latter scenario, a patient who incorrectly believes that the tablet has not been taken yet may take another tablet, which results in an inappropriate dose being taken, which may have safety consequences. These are examples of problems that can and do arise in the correct implementation of an extremely simple regimen, and many regimens are far from simple. Lack of compliance with a properly prescribed and dispensed drug regimen is one of the greatest impediments to successful pharmacotherapy at the public health level. (The term adherence is also seen in the literature: while there can be differential nuances in meaning, the similarities far outweigh them.) A given patient’s lack of compliance can be unintentional or intentional, and there are also complex behavioural, cultural, and psychological issues that come into play. Working for and with patients, individually and more widely, to increase levels of compliance is both a public health and a moral imperative. The interests of many professions in improving compliance are reflected in the fact that the topic is addressed in the literature of many disciplines. This is certainly beneficial, but it can make locating related publications somewhat challenging. The multidisciplinary yet integrative approach taken by the Journal will prove most helpful in this regard. The range of present and future contributions is exemplified by the papers published in this inaugural issue. Consideration of just a few of the papers’ titles - “A Patient-Centric Approach to Adherence”, “Addressing the Patient Factor in ePRO to Improve Compliance”, and “Patient Compliance, ePRO and the Role of the Care-giver” - indicates a strong focus on the patient. More detailed reading reveals that the roles and perspectives of additional stakeholders in integrated pharmaceutical medicine are represented, e.g., nurses, pharmacists, care-givers, and sponsors. This is also a field where behavioural scientists and psychologists can make significant additional contributions. Managing Editor Mark Barker and the journal’s Editorial Advisory Board are to be congratulated for bringing this new journal to the healthcare readership. I wish them all every success, and I look forward to reading the journal on a regular basis.

Volume 1 - Issue 1

Patient Compliance - the Right Journal at the Right Time

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Editorial Advisory Board Andree Bates, Managing Director, Eularis Anna Dirksen, Senior Manager, PSI Behavior Change Chris Penfold, Vice Chairman - East Midlands Packaging Society, Consultant, Freelance Packaging Specialist Dian Bryson, Managing Partner/VP Patient Strategy & Outcomes for Inspired Health Strategies Edwina Rogers, Executive Director of the Patient Centered Primary Care Collaborative Elisabeth Moench, President & CEO of Medici Global Helen Lawn, Managing Director, Helen Lawn & Associates a healthcare PR and communications agency Isabelle Moulon, Head of Medical Information Sector, European Medicines Agency Jay H. Bolling, President and CEO, Roska Healthcare Advertising Joseph Bedford, Director of Marketing Almac Clinical Technologies Laura Bix, Assoc. Prof. School of Packaging Michigan State University Louis A. Morris, Ph.D., is President of Louis A. Morris and Associates, Inc Mark Duman, Managing Director , MD Healthcare Consultants Michael Wong is Managing Director at hcCatalyst Peter van Iperen, Experienced Pharmaceutical Professional Phill Marley, Packaging Account Manager, Global Quality Operations AstraZeneca Ronald E. Weishaar, Executive Director, Observational Research, PharmaNet Development Group Saurabh Jain, Director of Patient Value Services and CME Solutions at Indegene. Steve Kemp, Business Development Director at Brecon Pharmaceuticals and Vice-Chairman of HCPC Europe Tassilo Korab, Co-founder of HCPC Europe (Healthcare Packaging Council) Vassilis Triantopoulos, CEO of BIOAXIS Healthcare Walter Berghahn, Executive Director, The Healthcare Compliance Packaging Council

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Volume 1 - Issue 1


Patient Story

Choosing Not to Take Medication: How Patients can Help Other Patients get Better The most common opinion of patients who don’t take their medications is they’re forgetful and need reminders. This may be true of some people, but many or perhaps even most actually choose not to take their medication. While the idea that a patient deliberately chooses not to take their medication as their doctor has ordered may not seem rational or even sane, as Dr Melissa Hunt (Associate Director of Clinical Training at University of Pennsylvania) explains, “Adherence is not simply blind compliance. Adherence is an active and voluntary choice by the patient.” Take Leonard, for example (name and story changed for confidentiality). His doctor said he had to start weekly injections to control his life-threatening condition. Unfortunately, like many people, the thought of pushing a needle into himself was not something that Leonard was comfortable with. To overcome his fears of self-injection, a nurse explained the best ways to do this and even gave him the drug’s website where there was more information on self-injection. However, the first two times that he injected himself, Leonard felt terrible. The injections made it impossible for him to function during the day. As he explains, “The injections made me feel like crap. I couldn’t do anything, didn’t want to talk to anyone.” So, Leonard did what many do - he stopped taking his medication. He did this because not being on treatment felt better than being on treatment. In his own mind, he had weighed the pros and cons of taking versus not taking his medication. No amount of education about his disease would change his mind, because he already knew it. His doctor had indeed explained the disease and its ramifications. An illustration of this weighing process for a patient diagnosed with glaucoma is depicted below: Only the example of another patient facing the same conditions and the same problems would change how Leonard weighed the pros and cons of taking or not taking his medication. When he described to another patient with the same condition about how terrible he felt after taking his injections, Leonard got this advice from this patient; “Before I inject myself, I drink tea, coffee, water, juice, whatever. And, I drink a lot right after each injection. The times that I don’t drink that much, I feel bad. So, now I make sure that I always carry a bottle of water with me wherever I go.” This advice got Leonard back on his medication. Patients who have figured out the “tips and tricks” to taking a medication can truly help other patients. When a patient is able to hear the story of another patient, to hear how they have taken their medication and dealt with their disease, then they will feel less hesitant in facing their medical problems. The power of patients to help other patients was recently validated in the randomised clinical trial published in the Annals of Internal Medicine, “Culturally Appropriate Storytelling to 8 Journal For Patient Compliance Strategies to enhance Health Outcomes

Improve Blood Pressure”. The research team, led by Dr Thomas K. Houston (a researcher at the University of Massachusetts Medical School in Worcester and the Veterans Affairs Medical Center in Bedford, Massachusetts), was trying to determine whether storytelling can be an effective way to teach patients about hypertension and improve blood pressure control. The randomised, controlled trial involved 299 patients who received a series of three DVDs (delivered at baseline, three months, and six months). Patients in the intervention group received these DVDs that contained patient stories. The comparison group received an attention control DVD that covered health topics not related to hypertension. In short, the researchers were seeing whether listening to hypertension stories would help these patients. The researchers found: “The storytelling intervention produced substantial and significant improvements in blood pressure for patients with baseline uncontrolled hypertension.” Another benefit of storytelling with patient compliance is the confidence and continued compliance that can be gained by a patient by sharing their experiences with others. A teacher leads by example, and since patients can teach each other, they will hold themselves to a higher standard. A young female patient, Sarah , had an exhausting diagnosis of Crohn’s disease that was preventing her from being able to function in her daily life. Because of her medical condition, she was forced to withdraw from college and move back home. After multiple admissions and attempts to avoid surgery and the creation of a colostomy, she had become depressed and uninterested in her daily life. Sarah was encouraged to share her story with others, through the use of a blog or other social media tool, so that she could have the ability to help others. By using social media, the patient would have the ability to maintain privacy and anonymity if Volume 1 - Issue 1


Patient Story preferred, but could still experience the connections that may help her cope with her illness. Since she was feeling helpless herself, hearing that she may be able to positively impact the lives of others was nothing short of inspirational to her. By the end of her hospital stay she was no longer concerned with the potential of a colostomy creation, but rather was excited at the prospect of sharing her experiences as a patient with others. Her parents were also praising the nursing staff for helping the patient to regain her sense of purpose.

Similarly, in the Annals of Internal Medicine study “Culturally Appropriate Storytelling to Improve Blood Pressure”, Dr Houston and his colleagues used storytellers “drawn from the patient population”. They used inner-city African-Americans because the patient population was inner-city African-Americans with hypertension. In other words, a peer - a person that patients can relate to who has gone through the same experience and who through that experience is able to provide behaviour to model after and which is medically relevant. For Leonard, he found that example in another patient. Not from an educational pamphlet or even a healthcare professional, but from another patient going through the same treatment that he was. For Sarah, she found that, by helping others, she was able to help herself get back on treatment. After snow has fallen, and the road is no longer visible, the journey can be made easier when you follow the tracks already laid in the snow.

What explains the power of storytelling to change patient behaviour? Dr Jay M. Pomerantz (Assistant Clinical Professor of Psychiatry at Harvard Medical School) describes how he has used storytelling to improve patients’ health outcomes: Many psychotherapists adhere to psychotherapy protocols such as cognitive-behavioral therapy, interpersonal therapy, dialectic behavioral therapy, or psychoanalytically oriented psychotherapy. Nonetheless, what actually goes on between therapist and patient is often variable and sometimes unique. One method I use involves storytelling, usually with the hope of producing insight, correcting a cognitive distortion, or providing context for an unusual feeling or happening. All of my stories are offered as a reaction to what patients are telling me. As I listen to patients, I wonder why they are telling me these vignettes of all the many subjects that they could talk about—past, present, future, imagined or real, sad or joyful. While listening, I always have inward musings, images, and stories. It seems that I engage in constant “free association,” which Freud recommended for patients in psychoanalysis but which I seem to have adapted as a therapeutic tool. More often than not, I will share some of these thoughts with my patients, usually in the form of a story. Over the years, I have developed almost blind trust in these associations, and they may account for what clinical success I have had in both individual and group psychotherapy. Fundamentally, Dr Pomerantz is telling a story that his patients can relate to and is medically relevant. In short, that story must have a point; and that point is to show how to be adherent to physician-prescribed medication.

References 1. The magnitude of the problem suggests most patients are non-adherent. According to the New England Healthcare Institute, $290,000,000,000 is what it costs annually because of poor adherence. 2. Dr Melissa Hunt, Associate Director, Clinical Training, University of Pennsylvania. 3. Houston TK, Allison JJ, Sussman M., Horn W, Holt CL, Trobaugh J, et al., “Culturally appropriate storytelling to improve blood pressure. A randomized trial.” Ann Intern Med. 2011;154:7784. 4. Name and identity changed to protect patient confidentiality. 5. “Storytelling as a Psychotherapeutic Technique” http://dbt. consultantlive.com/display/article/1145628/1494081 6. http://articles.boston.com/2011-03-21/lifestyle/29351917_1_ stories-storytelling-medical-advice

Hence, not all patient stories are good adherent stories. As Dr Ben Gerber (Internal Medicine, Assistant Professor of Medicine, University of Illinois, Chicago) explains, for a story to be medically helpful, it must provide: • basic information • emotional support • model behaviour • “a more realistic sense of the good and bad than the doctor does” www.JforPC.com

Brittney is a registered nurse and functions as a staff nurse, working the night shift on a medical surgical floor. She blogs about her nursing experiences at www.thenerdynurse. com. She also is a contributing writer to Nursinglink on www.monster.com and senior editor at www.myrealitytech.com. Email: thenerdynurse@gmail.com Michael Wong is Managing Director at hcCatalyst (www.hcCatalyst.com) and has developed a patient-to-patient solution to improving adherence by getting adherent patients to tell their stories to and dialogue with non-adherent patients – for more, see http://wp.me/P1fYJ7-i7. He blogs on ideas beyond standard healthcare thinking at www.boxcuttersinc. wordpress.com/. Email: mwong@hccatalyst.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 9


Watch Pages

Will FDAAA (REMS) bring Therapy Compliance to the Next Level? The Administration Amendments Act of 2007 (FDAAA) provides a new statutory framework and authority for the FDA to require a Risk Evaluation and Mitigation Strategy (REMS) for drugs and biologics. Specifically, FDAAA permits the FDA to require the applicant of a New Drug Application, Biologics License Application, Abbreviated New Drug Application or a supplement thereof to submit a proposed REMS as part of the application prior to approval if the Agency determines that it is “necessary to ensure that the benefits of the drug outweigh the risks of the drug.” The EMA demands similar strategies. All this underlines the importance of patient safety and patients’ protection against the expected and unexpected during drug therapy. Risk Mitigation Recent safety issues with approved drugs, resulting in the withdrawal of these drugs (e.g. Vioxx, Avandia), caused the regulators in Europe (EMA) and the US (FDA) to move in the direction of asking for drug risk mitigation plans. For every (new) drug, a risk mitigation plan must be in place. During the development phase of the drug the company should already perform data mining exercises to make sure possible side-effects specifically related to the compound will be picked up. This task needs to be extended throughout the entire life-cycle of the drug. From the preclinical stages you should begin to get a picture. Then, when a company enters into human studies and as it moves through the different stages of testing in man, a good risk management plan will incorporate all of the issues that are found in both preclinical and clinical development. Known risks, such as prolonged QTc interval, liver toxicity and kidney failure might be identified. Also, the definition and assessment of each risk will begin whilst quantifying those. All findings need to be incorporated into a sound risk management plan that needs to be submitted to the regulators, and will be examined closely during the drug approval process. In addition, the REMS plan needs to be updated regularly and will be reviewed again 18 months, three years and seven years after receiving a marketing authorisation. In the regulatory process three important features of (new) drug compounds are still being evaluated; quality, efficacy and safety. With the recent regulatory development in mind it is fair to state that the safety of the patient is paramount. Patient Compliance Where does compliance come into play? If one takes a look at the above it is obvious that pharmaceutical companies need to know whether or not a patient took the medication as prescribed by the physician. We all know that in real-life situations only roughly one-third of the patients completely comply with the instructions given by the physician, one-third of the patients more or less comply, and one-third do not comply. This rule of thumb applies basically to all (chronic) indications, even in life-threatening diseases. The fact that 10 Journal For Patient Compliance Strategies to enhance Health Outcomes

patients experience difficulties with their therapy compliance in more severe indications is clearly demonstrated by a finding of non-compliance in patients with chronic myeloid leukaemia. These findings were published by Lucien Noons et al. in Blood 2009; 113:5401-5411. This paper showed that although the use of the pharmaceutical studied might prolong the life of the patients dramatically, only 14.2% of the patients were perfectly adherent, with 100% of the prescribed drug taken. 71% of the patients took less drug than prescribed. Interestingly, 14.8% of the patients took more than the prescribed dose, even up to 202%.I am convinced that the latter will have an impact on the occurrence of side-effects. That brings me to the importance for pharmaceutical companies to know exactly how their products are used. A relevant aspect is of course the therapy compliance of the patients. Imagine that an unsuspected serious adverse event pops up during the life-cycle of the block-buster drug, from a number of “well-documented” case forms. The ultimate consequence is that the compound needs to be taken from the market and the marketing authorisation is suspended. I realise this is a very serious sequence of events and will not occur frequently. However, most companies currently have no clue if the patient took the drug at all and furthermore, if the drug was taken in the correct dose, etc. Taking this fact into consideration and looking at what might happen, I believe that this is a frightening perspective for most pharmaceutical companies. What if the compliance behaviour had been known and it turned out that the patients suffering from the grave safety issues did not take their drug at all, or at a very high (over)dose? I think it is only fair to state that a pharmaceutical company needs to know what happens with its compounds in a naturalistic setting. With the introduction of the REMS obligation it is a matter of time before pharmaceutical companies will furnish their products with compliance enabling out-of-the-box. What we need is a reliable, affordable way to furnish pharmaceutical products during the manufacturing process with a compliance measurement tool. This will bring the entire discussion related to safety a tremendous step forward. Peter van Iperen has 15 years experience in the pharmaceutical/healthcare business area. Reputed Top 10 pharma companies, in various executive positions, have employed him. He, together with his business partner Willem Kort, pioneered in the practical application of therapy compliance, i.e. the Dutch DIOVAN 160 pilot. Also, he provided impetus to numerous clinical multi-media initiatives, amongst others special interest clinical marketing communications. He holds a PhD in Bio-Pharmaceutical Sciences. Peter van Iperen is member of the editorial board of the Journal for Patient Compliance. Email: pvaniperen@me.com weblink: www.fda.gov/DrugsDrugSafetyPostmarketDrugSafety InformationforPatientsandProviders/ucm111350htm Volume 1 - Issue 1


Watch Pages Pharmacovigilance and New Legislation: The Role of Patient Compliance With the globalisation of the pharmaceutical market, the current system of EU pharmacovigilance is changing. How is this affecting pharma and patients? Until recently, patients’ non-compliance to treatment was believed to be of a non-intentional nature. More and more evidence though has been brought to the attention of stakeholders to show that in many cases patients make conscious decisions when it comes to not following their recommended course of treatment. The World Health Organization (WHO) has stated that 76% of patients consciously choose not to adhere to their medication or their specified regime, whilst only 24% of not following the adequate treatment is due to forgetfulness.1. Experiencing unpleasant side-effects is one of the most cited reasons for treatment drop-out. A Dutch study that interviewed non-adherent patients has revealed that their major concern was related to adverse events. Of the 232 patients that were examined in this study (using the inclusion criterion of chronic prescriptions for long-term medicines) an astounding 46% were not refilling their prescriptions over three months. A quarter of these patients stated that the reason for not refilling their prescriptions was because of adverse events.2 Any adverse reaction, covering noxious and unintended effects which are the result not only of the intended use of a medicinal product, but also the possible misuse and abuse, falls under the adverse event category, and the pharmaceutical companies have an obligation, imposed by pharmacovigilance law, to report those to the authorities whenever they occur. Late last year, the European Parliament and Council published an amended legislation which will become applicable from July 2012. The current system of pharmacovigilance in the EU has been established for a number of years and the authorities considered it was necessary to improve it. The reasons for improving the current system of pharmacovigilance in the EU, according to the European Commission, are closely related to the fact that it is a complex system where potential duplication of effort and confusion of responsibilities, particularly in the context of the introduction of innovative products and innovative technologies, are likely to happen. With the globalisation of the pharmaceutical market, products often enter different global markets simultaneously, with the exposure of large numbers of patients occurring in a short period of time, making it harder for the system to perform unless optimised. Some of the most important improvements in the new Regulation and Directive on Pharmacovigilance include setting out clear tasks and responsibilities for all parties involved in the EU pharmacovigilance system, improving decisionmaking procedures and using resources more efficiently, involving stakeholders in pharmacovigilance, including through direct patient reporting of suspected adverse drug reactions, strengthening communication and transparency on medicine safety, and strengthening companies’ pharmacovigilance systems.3 During the last few years, pharmaceutical companies have also shifted their focus in pharmacovigilance operations from “compliance” to “productivity”. Viewed by most executives as a non-strategic “cost centre”, pharmacovigilance, which is mainly 12 Journal For Patient Compliance Strategies to enhance Health Outcomes

concerned with product safety, has become a critical issue in keeping products on the market. At the same time companies are receiving a growing number of safety reports, and authority initiatives such as the new European pharmacovigilance law further increase these numbers. Presently, most pharmaceutical companies are increasingly concerned about how to process these safety reports at a lower cost.4 A natural evolution is to place these responsibilities with third parties, such as patient adherence providers. A patient support programme allows the pharmaceutical company to achieve more than one goal. Reducing the risk of patient treatment discontinuation due to adverse reactions to the prescribed medication seems to be the most obvious, but there are also the just-discussed benefits associated with pharmacovigilance compliance. Patient support providers are trained according to the pharmacovigilance requirements and all the data is collected in full confidentiality and aggregated for interpretation. This level of management over the adverse events reporting has never known such scale before the implementation of support programmes. Now, it has become more and more clear that it is only one of the reasons why such projects are not only highly beneficial, but potentially a must from a pharmacovigilance perspective. Patient compliance programmes are being refined and tailored with every new reality of the healthcare world. They are not set in stone, and in the same way the legislation is continuously improved and adapted. The patient is becoming more informed and is being given a say in his/her course of treatment, making it rather obvious that a tailored communication will only increase their satisfaction and treatment outcomes. With every change taking place in the new reality, adherence and support programmes are becoming the essential tools, which may possibly be able to address a multitude of other aspects, still to be discussed. References: 1. WHO Report 2009 2. Bioaxis Article: JC Hugtenburg et al. Initial phase of chronic medication use; patients’ reasons for discontinuation. British Journal of Clinical Pharmacology 2005 61: 352-354. SD Young, DM Oppenheimer. Different methods of presenting risk information and their influence on medication compliance intentions: results of three studies. Clinical Therapeutics 2006 28: 129-139 3. The EU Pharmacovigilance system. wwwec.europa.eu/health/ human-use/pharmacovigilance/index_en.htm, accessed March 2011 4. Albani, C. and Tabata, Y., Pharmacovigilance: Moving from productivity concern to strategic asset? www.pharmafocusasia. com/knowledge_bank/articles/, accessed March 2011 BIOAXIS Healthcare is a leading provider of end-to-end patient support and adherence services and solutions, strategically positioned to serve clients and affiliates on a global scale. The company’s proprietary technology and expertise to run unified patient support & adherence programmes with essential data feedback deliver ‘healthy outcomes’ to pharmaceutical companies in a cost effective way. . Email: info@bioaxis.eu. Volume 1 - Issue 1


Watch Pages

Patient Compliance, ePRO and the Role of the Care-giver

Sponsor companies are increasingly required to employ methods for patient-reported outcomes (PROs) that ensure timely, accurate and attributable data collection, as well as to improve patient compliance. In many drug trials, electronic patient-reported outcome (ePRO) systems, particularly electronic diaries (eDiaries), have been shown to be an effective and superior method of driving patient compliance when compared to paper-based methods. ePRO systems can be set up for real-time completion, eliminating errors or bias due to patient recall. The quick availability of data allows sponsors to track compliance closely and intervene with remediation measures when required. ePRO can also be used whether data is being reported by patients themselves or by their care-givers, such as in the cases of pediatric studies, and when studying diseases with severe motor symptoms or cognitive impairment. Patient and Care-giver Compliance A common misconception is that eDiaries would be too complex or time-consuming for some patients (for example elderly) or their care-givers to use for PRO data collection, resulting in poor patient and protocol compliance. Metrics-based ePRO vendors that measure patient compliance-to-protocol tell a different story; the elderly are actually one of the most compliant groups, with an average of 92% compliance, whereas the presumably most ‘tech-savvy’ groups of teenagers and adults have the lowest compliance rates, implying little correlation between technical expertise and ePRO compliance. Several reasons for this may be that: • Elderly patients generally have more time, whereas adults and teenagers have busy schedules • Elderly patients are typically more concerned about their 14 Journal For Patient Compliance Strategies to enhance Health Outcomes

health •C  are-givers of elderly patients may be more concerned about the patient’s health and are therefore more compliant •O  lder generations may be more compliant when receiving and following instructions •M  odern ePRO technology and good diary design can be intuitive for the patient Similarly, compliance in infant and children populations is also high, most likely because parents want to provide the best care for their child and comply with instructions to ensure this. Which ePRO attributes enhance patient and care-giver protocol compliance? What is critically important to ensure patients and care-givers are compliant with data entry, medication intake and the visit schedule? Proactive eDiary Design A key principle is to keep the ePRO design simple, to avoid completion difficulties and confusion. The device should guide the patient or care-giver in a logical way to perform all the required tasks at the correct times. Simple design elements that ensure data entry with minimal errors and allow for fast completion include the use of: o Audible alarms with instruction texts, such as: “It is time to fill in your evening diary” o Questions with pre-set answers (“Yes” or “No”) o Radio buttons or drop-down single answer selection from a list of options o Soft edit checks for clinical values, with normal ranges and upper and lower data entry limits that trigger data error alerts o Avoidance of free text data entry Volume 1 - Issue 1


Watch Pages For studies with more complicated requirements, eDiaries can be designed to capture specific events. For example, in a hemophilia trial, eDiary design can capture bleeding events and associated self-injections and utilise reminders for followup treatment efficacy questions to be answered in line with protocol requirements, as shown in Figure 2. Such a design allows patients or care-givers to rely solely on the eDiary to guide them on what to do at any given time, therefore providing more proactive support than they might get in a normal clinical setting. eDiaries can also be used to provide reminders about the expected duration of forthcoming visits, together with what patients need to take to that visit and the tests planned for that visit. They can even remind patients to fast before a blood draw visit. These design elements make the eDiary device more than just a data collection tool, but also a personal clinical trial assistant for the patients, care-givers and study sites. Active Remote Monitoring Remote monitoring tools for the investigator sites and study teams add another layer of checks that help to improve patient compliance. When study protocols have a specific study medication intake schedule or limits for rescue medication use, sites need to be able to track medication intake remotely in order to be able to intervene when problems are observed, as non-compliance with the study medication regimen is a significant issue for many studies. Real-time access to the patient’s reported medication intake data, via reports such as that in Figure 4, together with automated email alerts when issues are detected, can help minimise this. Figure 1: CRF health proprietary ePRO compliance metrics

Figure 1: Sample timed follow- efficacy question

Figure 3: Visit reminder screen

Figure 4: Sample medication compliance tracking report

www.JforPC.com

Challenging Study Populations With diseases that result in significant motor symptoms or impact on cognitive abilities such as Parkinson’s, Alzheimer’s or multiple sclerosis, ePRO systems might seem complicated and be considered less user-friendly than paper-based data collection. Recently CRF Health and Oxford Outcomes coordinated a focus group of patients with Parkinson’s disease to investigate this aspect. After basic orientation, patients who were able to use an eDiary preferred this method over paper. Some patients with severe symptoms could not use either method, but commented that their care-givers would prefer the electronic version. Similar, if not even more positive, results were collected in a usability test with twenty patients with multiple sclerosis using a large-screen tablet PC device. Many individuals from both groups noted that one of the key benefits is the ability to easily correct data entry mistakes with the electronic device. eDiary designs can accommodate both patient and caregiver functionality on the same device. When a care-giver is involved, it is even more important to have clear instructions in the eDiary that will guide them to follow the study and ePRO data entry schedule more closely. It is also important that the ePRO system used has a care-giver module that fulfills all the regulatory requirements for this type of data entry. All eDiary users must have their own user accounts so that the data can be attributable. In conclusion, in studies where care-givers enter the PRO data on behalf of the patient, such as studies with infants or subjects with Parkinson’s disease, dementia or Alzheimer’s disease, compliance can be maintained at consistently high levels. Proactive eDiary design, visit reminders, and active remote monitoring are critical functions and necessary requirements to maintain high levels of patient compliance in all patient settings, including those that rely on care-giver support. Rohini Beavon, PhD is Director of R Beavon Solutions Limited in the UK and is currently a freelance clinical research professional to the pharmaceutical industry. She has worked in the pharmaceutical industry for 12 years, most recently for Pfizer (formerly Wyeth) as a Clinical Project Manager and Clinical Scientist and was educated at the University of Liverpool and the University of Surrey. Email: Rohini.beavon@RBeavonSolutions.co.uk Kai Langel has worked with CRF Health since the company’s inception in 2000 and is one of the pioneers in the ePRO industry. During this time, Kai has been involved in all aspects of ePRO operations from system design to deployment and support. Kai spent 5 years in the United States where he was responsible for building CRF Health’s technical delivery team. He is currently based in Europe in a consultative role providing advice and guidance to both customers and CRF Health’s internal teams on technical, operational and regulatory issues. Kai is a true global ePRO expert, having worked both in the United States, Europe and more recently in Japan and Asia. Email: Kai.langel@crfhealth.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 15


Regulatory & Market Place

Medication Management and Health Outcomes Welcome to the Journal of Patient Compliance! It is a pleasure to be part of this inaugural issue. While many publications have looked at the overall healthcare picture, few have focused on the issue of medication adherence in patients. It’s a bit strange considering the magnitude of the problem - some US $300 billion annually in the United States alone. While this statistic is found in many places, the most recent and notable listing is in the New England Healthcare Institute paper “Thinking Outside the Pillbox”, 2010. The overall impact on the healthcare system from medication non-compliance, not to mention the oft-ignored patient, is simply staggering. I’m not going to spend any time reviewing the horrific statistics surrounding non-compliance - you already know them, that’s why you’re reading the Journal. More importantly, we should invest our time in finding solutions. We do need to spend a bit of time looking at the past, though. Understanding the path that led us here is important in evaluating how to navigate away from this tragedy. We find ourselves in a curious situation. The manufacture of pharmaceuticals is well regulated from inception to production, yet the misuse of these same products causes hundreds of billions of dollars of damage on an annual basis, with immeasurable impact on the lives of the patients and their families. There is no other product category with such wide use where similar performance is tolerated. Whether it’s the food, appliance, automotive or airline industry, safety issues are identified . . . then rectified. How can the regular mismanagement of pharmaceuticals not demand the same scrutiny as these other categories? Part of the problem lies in the supply chain process. The pharmaceutical manufacturers by all means have done the work required and requested of them; designing and developing chemicals for the purpose of fighting disease and improving health; packing and transporting them to market for distribution in a wide variety of settings from retail pharmacy to institutions, etc.. Along the way, we seem to have neglected that these drugs need to be taken properly in order to fulfill their mission. Unfortunately, in the US market, we still have an antiquated system where the pharmacist repacks the great majority of pharmaceuticals into little brown vials for each patient. This little vial was developed while Eisenhower was president. You remember Eisenhower, the first post-WWII president? This was right around the time that Elvis Presley was singing Heartbreak Hotel. Sadly, 55 years later the King is gone, but the little amber vial is still going strong. This pharmacy-filled vial made perfect sense when we had compounding pharmacists, but that practice only applies to a tiny portion of pharmaceuticals delivered today. The European and Asian markets have fared better in terms of the primary packaging, opting primarily for blisters instead of manually-filled vials, but these markets are still lacking usable graphics or print reminders to aid adherence. Part of the problem lies in the regulatory disconnect between the pharmaceutical manufacture and the pharmacy. Responsibility for manufacture and responsibility for patient administration of 16 Journal For Patient Compliance Strategies to enhance Health Outcomes

the product reside in different industries. To further complicate the subject, administration of pharmaceuticals takes place in a large number of varied settings that require different functions from the dispensing package. This does not excuse the lack of innovation in pharmaceutical packaging, though. Poor primary packaging pushes consumers to seek home solutions for medication organization in an attempt to aid their own compliance. This quite often means little upscale ice cube trays with lids where consumers cram multiple medications into single cavities. Why should users be forced to repackage medications in the home because the market neglected to provide a functional package? The list of potential problems with this system is endless, the most prominent being dosing errors, either through omission or overdosing. These packages allow drug to drug contact, something that is forbidden in the pharmaceutical manufacturing sector. These trays do not provide protection of the product from the environment, which can potentially impact drug efficacy. Why do you think the pharmaceutical manufacturers spend the time and effort on package stability studies? To make themselves feel good? They do it to ensure that the product is protected from the environment, primarily oxygen and moisture, to ensure product performance and efficacy. People now regularly repackage life-saving pharmaceuticals in the home simply because the packaging delivered in pharmacy offers no adherence support; little or no usable information about the product, its intended use, the potential impact from poor adherence, nor the impact of the disease condition untreated. And product protection? Nowhere to be seen. In the last 40 years there has been an acceleration of technological innovation around consumer products and devices. The phone, not long ago, was bound to a wall, limited in movement to the length of cord you could tolerate. It’s hard to imagine or describe the quantum leap that the phone has taken. Today it’s almost silly to call it a phone. It is a mobile computer, camera, internet browser, GPS device. Oh yes, you can make phone calls, too, although texting seems to be fast replacing conversation. Now, much to the medical profession’s credit, they have begun to latch on to this technology in support of medication adherence. Both e-mail and text reminders are growing in use, but those apps alone will not solve the problem. Visual reminders need to travel with the products. Better information needs to be constantly available. Packaging for many consumer products is no different. The materials and functional forms that exist today were not even on the drawing board 40 years ago. What happened in pharmaceutical packaging? How did it miss the revolution and evolution that has impacted everything from foods to personal media devices? Better pharmaceutical packaging solutions are out there; they simply need to be adopted. The responsibility for this better packaging does not reside solely with the pharma manufacturer, nor should it. To be efficient, packaging needs to take place closer to the patient when required package function is known. We have a robust Volume 1 - Issue 1


Regulatory & Market Place worldwide secondary packaging market for pharmaceuticals, and it has become adept at responding to late stage customisation needs when confronted with local language requirements. Package form and function is no different. Some dispensing markets have different functional needs from the package, but the decision about the pack form can only be made when we know which market the pharmaceuticals will be sold to. So what should better packaging provide? The basics of product protection are a given (or they should be) but the real missing component is communication. The package should provide information to the consumer about the product and the disease it is intended to treat. The package should remind the patient (and the care-giver) of the timing of the dose and provide a visual check of whether the dose has been taken. This basic feedback is critical in any care situation. Think about how much care-givers and physicians alike rely on feedback from the patient in making health decisions. A care-giver visits the home; “Did you take your medication this morning ?” The patient response elicits action (or inaction) from the care-giver which could result in over or underdosing if the patient reply is not accurate. The great majority of patients who might receive home care are elderly. How often might the response be incorrect? And not simply due to memory - as numerous studies have pointed out, the reasons for noncompliance are many. There could be any number of reasons for an inaccurate response, and yet the response is all the care-giver has in order to make a decision. In the physician’s office the situation is quite similar, but the impact could be much worse. Take for instance blood pressure medication. A patient visits the physician and their blood pressure is high. The natural question from the doctor or nurse is “Are you taking your medication ?” I would not care to guess what % of patients answer “Yes” when the answer is really, “sometimes,” “I can’t remember,” or even “No.” The professional is now put in the position of making a health decision based upon faulty information. Suppose the dose strength is increased in response to high blood pressure numbers and a supposedly “compliant” patient. Now the patient is on a stronger dose than needed and after the doctor visit they may be a bit more compliant for a while. The old prescription for the lower strength is discarded (more waste) and the new prescription may or not have side-effects, since it was not prescribed with accurate data. How often is this happening in our health systems today? So, how can better packaging help the scenarios outlined above? One of the simplest and most effective package improvements is the unit dose calendarised blister pack. Think birth control compact. Don’t take my word for it. The following statement is found in the IoM (Institutes of Medicine) report from July 2006 in support of unit of use drug packaging: “The strategy of using calendar blister packs could help large numbers of patients (including seniors, children and those challenged by cognitive, physical or functional impairment) take their medication more reliably and safely and ENHANCE THEIR TREATMENT OUTCOMES.” This package form has demonstrated adherence rates in the 95% range. But the patient reminder is only the start, because now the primary care-giver has information in the form of an empty cavity next to the date which says, “Yes, my patient took their medication today.” So what else can we accomplish with packaging? There are three basic styles of package feature that can provide varying 18 Journal For Patient Compliance Strategies to enhance Health Outcomes

Volume 1 - Issue 1


Regulatory & Market Place degrees of useful information to and for the patient. They are: passive features, active features and interactive features. The goals of incorporating these features are basic: communicate, remind, engage and, verify. Passive features can take the form of simple educational graphics on the package. They are put in the path of the consumer and we hope they do some good. Active solutions: lights, buzzers or the features that will get the attention of the customer with similar hopes to the passive solutions. Even the calendar feature qualifies as active since its use leaves evidence of dispensing that can provide feedback to the patient and care-giver. Interactive solutions: now, beyond the simple package. Certain packages with embedded electronics provide feedback and elicit response from the patient. Some even incorporate internet-based or cellular feedback features to provide professional care-givers real-time data on patient adherence. This link is critical, since it provides the opportunity to intervene if a non-compliant patient is putting themselves in a dangerous situation. Call centres provide interactive solutions. Human to human interaction can be quite effective in prompting adherence, but unless we intend to have one half the world call the other half of the world they are an impractical long-term solution. And again, they exist due to poor primary packaging that does little to communicate or promote adherence. The goal at the end of the day is verifiable use. Family members, care-givers and health professionals need some way to know that a drug was taken by the patient. Only with verifiable use can we prevent adverse drug events (ADEs) that are responsible for as much as 28% of emergency room visits, 10% of hospitalisations, and 25% of nursing home admissions. One bright spot in all this is that there will be many allies in this battle going forward. What I am referring to is the growing number of pay-for-performance healthcare models that are evolving in every market. By shifting compensation measure to improved outcomes from one of patient volume, we will create a care-giver community that will view medication adherence not as a nice-to-have, but a necessity, since poor adherence by patients (even in their own homes) will lead to decreased compensation for the care-givers. In the US, CMS (Centers for Medicare and Medicaid Services) has set the stage with Medical Homes and Care Transition programmes. I encourage you to research these if you have not heard of them. When the healthcare provider’s financial bottom line depends on patients taking their medication, rest assured these providers will take an interest in medication adherence, and will drive change in product delivery which will include better, smarter packaging. I hope to be able to write to you soon on this new development. Walter Berghahn Currently Executive Director of the Healthcare Compliance Packaging Council, a not-for-profit trade association focussed on advancing medication adherence through better packaging design. Formerly, V.P. Packaging Technology for AmerisourceBergen Packaging Group also National Sales Director for Uhlmann Packaging Systems. 25 years packaging experience. B.S. Packaging Engineering, Rutgers University, College of Engineering. Email: walterberghahn@yahoo.com www.JforPC.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 19


Regulatory & Market Place

The Patient-Centered Medical Home and Medication Management The Patient-Centered Primary Care Collaborative (PCPCC) has more than 700 PCPCC members, including a number of large national employers, most of the major primary care physician associations, health benefits companies, trade associations, profession/affinity groups, academic centres, and healthcare quality improvement associations in the United States. The membership believes that the patient-centered medical home (PCMH) is an appropriate foundation to transform healthcare delivery to improve quality and lower costs. The principles and practices of PCMH align and enable care coordination, improved medication management, and quality improvement. The Collaborative advocates that payment reform should provide incentives consistent with this model. The Patient-Centered Medical Home The basic concept of the medical home is the primary care provider taking responsibility for a patient’s health and coordinated care — with the provider being compensated for his efforts. Exactly how pharmacists connect to the process needs further policy development, but is important to success in medication management. Clinicians practising in the highest level medical home will: • Take personal responsibility and accountability for the ongoing care of patients; • Be accessible to their patients on short notice, for expanded hours, and open scheduling; • Be able to conduct consultations by email and telephone; • Utilise the latest health information technology and evidencebased medical approaches, as well as maintain updated electronic personal health records; • Conduct regular check-ups with patients to identify looming health crises, and initiate treatment/prevention measures before costly, last-minute emergency procedures are required; • Advise patients on preventive care based on environmental and genetic risk factors they face; • Help patients make healthy lifestyle decisions; and • Coordinate care, when needed, making sure procedures are relevant, necessary, and performed efficiently. The Collaborative has a series of papers to explain the overlap and operation of various aspects of the healthcare delivery system and PCMH. This article borrows extensively and directly from work of the Collaborative, including from a resource guide publication styled “The Patient Centered Medical Home: Integrating Comprehensive Medication Management to Optimize Patient Outcomes” (PCPCC Guide). The Importance of Medication Management More than 3.5 billion prescriptions are written annually in the United States, and four out of five patients who visit a physician leave with at least one prescription. Medications are involved in 80 per cent of all treatments and impact every aspect of a patient’s life. The two most common drug therapy problems that patients receiving comprehensive medication 20 Journal For Patient Compliance Strategies to enhance Health Outcomes

management experience are (1) the patient requires additional drug therapy for prevention, synergistic, or palliative care; and (2) the drug dosages need to be titrated to achieve therapeutic levels that reach the intended therapy goals. According to the World Health Organization, adherence to therapy for chronic diseases in developed countries averages 50 per cent, and the consequences of poor adherence to therapies are poor health outcomes and increased healthcare costs. Drug therapy problems occur every day and cost money; drug-related morbidity and mortality cost this country almost $200 billion annually, exceeding the amount spent on the medications themselves. For example, Medicare beneficiaries with multiple chronic illnesses see an average of 13 different physicians, fill 50 different prescriptions per year, account for 76 per cent of all hospital admissions, and are 100 times more likely to have a preventable hospitalisation than those with no chronic conditions. The Institute of Medicine noted that while only 10 per cent of total healthcare costs are spent on medications, their ability to control disease and impact overall cost, morbidity, and productivity — when appropriately used — is enormous. According to the Institute of Medicine: Pharmaceuticals are the most common medical intervention, and their potential for both help and harm is enormous. Ensuring that the American people get the most benefit from advances in pharmacology is a critical component of improving the national health care system. The PCPCC guide was developed to provide a framework for integrating medication management in the PCMH as part of the practice redesign that needs to occur when individual and group practices transform into the PCMH. The guide also reinforces the need for payment reform to support the PCMH to include payment for medication management as an essential professional activity for effective integrated care. Comprehensive Medication Management Comprehensive medication management is defined as the standard of care that ensures each patient’s medications (whether they are prescription, non-prescription, alternative, traditional, vitamins, or nutritional supplements) are individually assessed to determine that each medication is appropriate for the patient, effective for the medical condition, safe given the co-morbidities and other medications being taken, and able to be taken by the patient as intended. Comprehensive medication management includes an individualised care plan that achieves the intended goals of therapy with appropriate follow-up to determine actual patient outcomes. This all occurs because the patient understands, agrees with, and actively participates in the treatment regimen, thus optimising each patient’s medication experience and clinical outcomes. Adherence to medications and recommended therapies works best when patients have a thorough understanding of all of their medications, including over-the-counter drugs. Appropriate steps include: 1. An assessment of the patient’s medication-related needs 2. Identification of the patient’s medication-related problems Volume 1 - Issue 1


Regulatory & Market Place 3. D  evelopment of a care plan with individualised therapy goals and personalised interventions 4. F  ollow-up evaluation to determine actual patient outcomes Significant evidence is accumulating to establish the positive impact that comprehensive medication therapy management has on patient outcomes. Patients who benefit most are those who: • have not reached or are not maintaining the intended therapy goal • are experiencing adverse effects from their medications • have difficulty understanding and following their medication regimen • are in need of preventive therapy • are frequently readmitted to the hospital Medication management now occurs at varying levels in all patient care practices on a daily basis. However, medication regimens are becoming very complex and specialised in patients who have an average of five co-morbidities and are taking an average of eight medications concurrently. The PCPCC guide uses the common elements of two definitions that describe this service in the medical home — the definition offered by the American Medical Association (AMA) when it provided current procedural terminology (CPT) payment codes for the delivery of medication management services and the definition provided by legislation for Minnesota Medicaid recipients. These definitions have the following five elements in common, relevant to the needs of patients being cared for in the medical home: 1. T  he service (medication management) needs to be delivered directly to a specific patient. 2. T  he service must include an assessment of the specific patient’s medication-related needs to determine if the patient is experiencing any drug therapy problems. A care plan is developed to resolve the problems, establish specific therapy goals, implement personalised interventions and education, and follow up to determine the actual outcomes the patient experienced from taking the medications. 3. T  he care must be comprehensive, because medications impact all other medications and all medical conditions. 4. T  he work of pharmacists and medication therapy practitioners needs to be coordinated with other team members in the PCMH. 5. T  he service is expected to add unique value to the care of the patient. The Value of Medication Management in PCMH The value of medication management in PCMH can be measured in a number of ways. First, the patient benefits from improved outcomes. In addition, the patient benefits directly from the increased individualised attention to medications and the role they play in his or her daily life. Third, physicians benefit when someone with pharmacotherapeutic expertise is able to help manage complex drug therapies. Physicians are able to dedicate more time to the diagnostic and treatment selection process, enabling them to be more efficient, see more patients, and spend more time providing medical care. In general, health plans, employers, and payers benefit tremendously when they pay only for medications that are safe, appropriate, and effective for the patient and his or her medical problem, and are 22 Journal For Patient Compliance Strategies to enhance Health Outcomes

used as intended. Keeping patients out of the hospital is one of the most costeffective outcomes, and providing comprehensive medication management to complex patients is one way to accomplish this. Another way to measure value is through the calculation of return on investment (ROI), or how much value the service adds compared to the cost of delivering the service. ROI data are frequently difficult to obtain and vary significantly, depending on the patient population being evaluated. However the ROI of medication management services has been established. The data from the delivery of this service are positive, with a demonstrated ROI of as high as 12:1 and an average of 3:1 to 5:1. ROI reflects an ability to decrease hospital admissions, physician visits, and emergency room admissions, and reduce the use of unnecessary and inappropriate medications. This is a conservative estimate; the ROI is likely to be much greater because practitioners routinely underestimate the impact on a patient’s life, and it is not easy to put a number on high patient satisfaction and physician acceptance. Integration of Pharmacists One principle of the PCMH is the team approach, and the composition of the PCMH team will vary based on a range of factors, including the specific needs of patients and the scope of services to be offered and/or coordinated. For patients on multiple or chronic medications, pharmacists, who are trained to provide comprehensive medication management services, have the necessary expertise to help them and their healthcare team in the PCMH maximise the benefits from the very effective medications available. Using an individual who can manage difficult, complex patients with medication problems will make the entire patient care team more effective and efficient. Payment policies should be aligned to (1) effectively support the medical home, (2) provide reasonable and adequate payment for pharmacists’ clinical services as an element of the scope of services that are eligible for payment to either the providers or the [medical home] practice, and (3) promote the achievement of higher quality, safer, and more effective therapeutic outcomes from medication use through enhanced provider collaboration. The effective integration of pharmacists’ clinical services within the patient-centered primary care medical home can include: • Access to pharmacists’ clinical services •D  evelopment, implementation, and monitoring of medication treatment plans, including an effective system for medication reconciliation that supports patients in their transitions among care settings, and includes knowledge and the skills of the prescribing professional(s) and pharmacists • I nnovative and flexible practice structures that integrate pharmacists’ clinical services •E  xpansion and effective use of health information technology must be promoted to support more complete integration of pharmacists as care providers within the medical home practice structure Alignment of Medication Management and PCMH Principles As a general matter, appropriate medication management aligns well with the principles of PCMH. The PCPCC guide notes the following relationships among principles. Volume 1 - Issue 1


Regulatory & Market Place • Personal Relationship with Physician or Other Practitioner. The therapeutic relationship is established and the patient’s medication experience is revealed and used to improve care. • Team Approach. The rational decision-making process for drug therapy is utilised and the assessment, care plan and followup of drug therapy is integrated with the team’s efforts. • Comprehensive/Whole Person Approach. All of a patient’s medications (regardless of source) are coordinated and evaluated to ensure they are appropriate, effective, safe, and convenient. • Coordination and Integration of Care. The intended therapeutic goals, which are made measurable and individualised to the patient, serve to coordinate and integrate the patient’s care with other team members. • Quality and Safety are Hallmarks. Drug therapy problems are identified, resolved, and prevented in a systematic and comprehensive manner to realise appropriate, effective, safe, and convenient drug therapy for the patient. • Expanded Access to Care. Physicians are extended, made more efficient and more effective through the optimal management of a patient’s medications. • Added Value Recognised. Clinical outcomes are improved, return-on-investment is positive, acceptance by patients is high, and physicians support the practice. More work needs to be done to transform practices based on a PCMH foundation. As we cross important areas such as medication management, it is important to continue to gain information and incorporate best practices into the definition of PCMH, and to the payment and other incentives in healthcare. References 1. P  atient-Centered Primary Care Collaborative. http://www.pcpcc. net. 2. http://www.pcpcc.net/files/medmanagepub.pdf  3. S ommers JP. Prescription drug expenditures in the 10 largest states for persons under age 65, 2005. 2008. Agency for Healthcare Research and Quality. Available at: http://meps. ahrq.gov/mepsweb/data_files/publications/st196/stat196.pdf. 4. T  he chain pharmacy industry profile. National Association of Chain Drug Stores. 2001. 5. C  ipolle R, Strand L, Morley P. Pharmaceutical care practice: The clinician’s guide. McGraw-Hill; 2004. 6. W  orld Health Organization. Adherence to long-term therapies: Evidence for action. 2003. Available at: http://whqlibdoc.who. int/publications/2003/9241545992.pdf. 7. J ohnson J, Bootman JL. Drug-related morbidity and mortality. Arch Intern Med. 995;155(18):1949-1956. 8. J ohnson JA, Bootman JL. Drug-related morbidity and mortality. Am J Health Syst Pharm. 1997;54(5):554-558. 9. E rnst, FR, Grizzle AJ. Drug-related morbidity and mortality: Updating the cost-of-illness model. J Am Pharm Assoc. 2001;41(2):192-199. 10. A  nderson GF. Testimony before the Senate Special Committee on Aging. The Future of Medicare: Recognizing the Need for Chronic Care Coordination. Serial No. 110-7, pp 19-20 (May 9, 2007). 11. C  enters for Medicare & Medicaid Services. National Health Expenditures. January 2008. 12. I nstitute of Medicine, National Academy of Science. Informing www.JforPC.com

the Future: Critical Issues in Health. 4th ed.:13, Available at: http://www.nap.edu/catalog/12014.html. 13. American Medical Association. Current Procedural Terminology. Chicago, IL, 2007. 14. CMS. Prescription Drug Coverage 2010 Call Letter. Available at: http://www.cms.hhs.gov/PrescriptionDrugCovContra/ Downloads/2010CallLetter.pdf. 15. Minnesota Statute 256B.0625 Subd. 13h, 2005. Available at: https://www.revisor.mn.gov/statutes/?id=256B.0625. 16. Isetts BJ. Evaluating Effectiveness of the Minnesota Medication Therapy Management Care Program. Final report. Available at: http://www.dhs.state.mn.s/main/groups/ buiness_partners/documents/pub/dhs16_140283.pdf. 17. Fera T, Bluml BM, Ellis WM. Diabetes ten-city challenge: Final economic and clinical results. J Am Pharm Assoc. 2009;49;38391. 18. Cranor CW, Bunting BA, Christensen DB. The Asheville Project: Long-term clinical and economic outcomes of a community pharmacy diabetes care program. J Am Pharm Assoc. 2003;43:173-84. 19. American Medical Association. Ibid. 20. CMS. Ibid. 21. Minnesota Statute. Ibid. 22. Nichol A, Downs G. The pharmacist as physician extender in family medicine office practice. J Am Pharm Assoc. 2006;46:77-83. 23. Roughead EE, Barratt JD, Ramsay E, et al. The effectiveness of collaborative medicine reviews in delaying time to next hospitalization for patients with heart failure in the practice setting. Results of a cohort study. Circ Heart Fail. 2009;2:424-8. 24. Isetts BJ, Schondelmeyer SW, Artz MB, Lenarz LA, et al. Clinical and economic outcomes of medication therapy management services: The Minnesota experience. J Am Pharm Assoc. 2008;48:203-211. 25. Cipolle R, Strand L, Morley P. Pharmaceutical care practice: The clinician’s guide. McGraw-Hill; 2004. 26. Carter BL, Rogers M, Daly J, Zheng S, James PA. The potency of team-based care interventions for hypertension. Arch Intern Med. 2009;169(19):1746-1755. 27. Harris IM, Westberg SM, Frakes MJ, VanVooren JS. Outcomes of medication therapy review in a family medicine clinic. J Am Pharm Assoc. 2009;49:623-627. 28. Integration of Pharmacists’ Clinical Services in the PatientCentered Medical Home: Policy Issues and Principles. Available at http://www.accp.com. Edwina Rogers currently serves as the Executive Director of the Patient Centered Primary Care Collaborative, a Washington DC trade association, responsible for the national Patient Centered Medical Home movement. Edwina has been a public policy expert for over 20 years and has worked for two Presidents and four Senators. Email: erogers@pcpcc.net

Journal For Patient Compliance Strategies to enhance Health Outcomes 23


Regulatory & Market Place

The Community Pharmacy’s Role in Patient Adherence How Pharma Firms can Support Pharmacies to Benefit Patients, Stakeholders, and their Bottom Lines According to the World Health Organization, between 30 and 50 per cent of medicines prescribed for chronic diseases are not taken as directed. Statistics for medicines that address acute diseases are better, but not by much. Non-adherence costs the pharma industry billions every year and leads to both disease escalation and deaths. But pharmacists can help. By working with pharmacies and helping to establish frontline services, pharma companies can help patients, stakeholders, and their bottom lines. The ideal relationship between pharmacies and pharma is one of “partnership,” according to Michael Holden,

24 Journal For Patient Compliance Strategies to enhance Health Outcomes

chief executive of the UK National Pharmacy Association. “Pharmacists see patients around four times as often as anyone else in the healthcare system, so we need to leverage that interaction to support adherence.” The Role of the Community Pharmacy Elizabeth Oyekan, area pharmacy director at Kaiser Permanente, the largest managed care organisation in the US, says this can be a “win-win-win” for patients, pharmacists, and pharma. “It’s a win for patients because they’re healthier,” she says. “It’s a win for pharmacies because their patients are healthier as is their bottom line. And it’s a win for pharma because they sell more drugs and spend less time and money searching for new ones.” Mark Ireland, director of pharmacy contract and project development at Boots, a leading UK pharmacy chain, agrees. “The [pharma] industry invests billions to prove the clinical effectiveness of its products,” he says. “This is hampered by patients failing to adhere to the medicines they are prescribed, causing governments and patients not to realise the full potential benefits.” The community pharmacy is a good place to start to turn this situation around. In the past few years, big box establishments have put community pharmacies under threat. While some community pharmacies have folded, others have proven resilient, fully embracing the “community” aspect of community pharmacy. “All of a sudden, throughout community pharmacy, everyone is focused on improving services and offering real value to the patient,” says Oyekan. Many pharmacies are already experimenting with value-added services. In community pharmacies in the US, medication therapy management (MTM) programmes have become popular. In addition to dispensing drugs, pharmacists in MTM programmes provide comprehensive reviews that check for medication appropriateness as well as problems with adherence and side-effects or adverse events. “In the future, community pharmacies will be service-based entities that will encompass a wide variety of service offerings under the umbrella of Volume 1 - Issue 1


Regulatory & Market Place medication therapy management,” says Jim Owen, director of professional practice at the American Pharmacists Association. In Europe, medicine usage reviews and chronic medication services are gaining traction. Adherence programmes use interactive voice recognition (IVR) tools to reach out to patients who are late picking up drugs. Simpler iterations involve pharmacists and nurses hitting the phone lines on weekends to reach out to patients. For example, CVS recently introduced its Patient Care Initiative and Kaiser unveiled B-SMART, a comprehensive manifesto for medication adherence in its community pharmacies. The Need for Systemic Support Despite the momentum behind value-added services, pharmacies still need help. “The pharmacist is at a tipping point when small things can make a big difference,” Holden says. “We have to put more ownership of treatment in the hands of patients and support them through education and behaviour change. The pharma industry has a major role in facilitating that.” Ireland points out that pharmacists manage a very complex supply chain and dispensing process that is highly regulated and controlled. This means there have to be strong operational processes and a more generic service for specific disease areas. “Pharma has a lot that it could offer to setting up such a programme,” says Ireland.

Holden highlights the usefulness of quick reference guides that provide clinical updates and share tips on how to handle certain situations or certain molecules. “If pharma can help community pharmacies work on systematising and standardising programmes, that becomes a value-added service as well as a win-win,” Oyekan says. On the adherence front, pharmacies are in need of predictive tools that proactively identify patients at risk of non-adherence. Merck, for instance, offers the Adherence Estimator, a threequestion form that 2010 research showed to be 86 per cent accurate in identifying patients at risk of non-adherence. “The bottom line is that we need to reduce the health burden of the patient, improve the care experience, and reduce overall healthcare costs,” Oyekan concludes. “Helping pharmacies better manage and dispense drugs to more adherent patients is a powerful way to accomplish that.” Andrew Tolve is a writer living in Atlanta, Georgia. His journalism has appeared in The New York Times Magazine, Slate, National Geographic Adventure, and Men’s Journal, among others. He is a regular contributor to eyeforpharma.com, where he specialises in the intersection of digital innovation and pharmaceutical sales and marketing. Email: atolve@gmail.com


Regulatory & Market Place

Patient Non-Adherence… The Truth We Can No Longer Afford to Ignore $US 280 billion is left behind each year due to industry failure to retain patients. Of the 3.8 billion prescriptions written each year, 1.3 billion, or 31%, will never get filled. 40% of the prescriptions that do get filled will not be taken as directed. 125,000 deaths and $US 100 billion in direct annual costs to the US healthcare system alone result from non-adherence. Experts conclude that if the pharma industry is to maintain its 3.1% growth rate through the patent cliff 2010-2014 it must find $US 64 billion in revenue. Then why is so little attention paid to adherence? Improving adherence represents an opportunity to increase revenues and improve patient outcomes while achieving the sales goals for which a company has already paid. The life sciences industry is finally starting to make the shift, but only very slightly and ever so slowly. Over the last few years several reports have provided direction regarding the hurdles the industry must face before it can hope to continue doing business in today’s climate: PricewaterhouseCoopers Pharma 2020 Ernst & Young Progressions 2011: Building Pharma 3.0 AT Kearney Pharmaceuticals Out of Balance: Reaching the Tipping Point They all state, essentially: • There is movement from treatment to preventative care • Patients and payers join providers as solid decision-makers in prescription fill rates, and overall health regimen adherence rates • Pharma can no longer simply provide the drugs, but also must provide supportive services for both patients and providers around those medications • The trend away from blockbusters means the traditional rep model will disappear and a stronger focus on patient communication will emerge • Changes in how R&D will work • Supply chain will be revenue-generating • New distribution channels will emerge, creating less dependence on the wholesaler Figure 1: Key findings; drivers and resistors for pharma

26 Journal For Patient Compliance Strategies to enhance Health Outcomes

If all of this data is true, then why is it, for the most part, that business continues to be run the same way as it was 20 years ago? •A  lthough there are fewer representatives, the rep model is still heavily dependent on talking to providers to generate prescriptions. •T  hough some reps worldwide meet with pharmacists and nurses, it still is not enough when the focus is adherence. •T  here is little attention paid to health educators. In fact it seems the further away someone is from generating the initial prescription, the less likely anyone from pharma will engage them; an unfortunate and costly decision, considering the converse could actually benefit patients and help improve adherence. In the US a discussion has begun around the rep model. Usually this conversation involves how to incentivise the rep, since behaviourists tell us that what we do is based on how we are incentivised. Recently, GlaxoSmithKline embarked on an earth-shattering journey - GSK abolished incentives based on sales, and instead, developed a service-focused business model. The jury is out on the effect this will have on their business, but just the same, Kantar Health reports observations that most pharmaceutical companies are preparing to follow suit with a service model in at least parts of their sales forces. These are good signs, nonetheless, as the patients can be better served in the end. Figure 2: The patent cliff; pharma needs to find an extra $64billion in 2014 if it is to off set the patent cliff

There is a lot of discussion around how to prop up the research and development of new therapies. As patents expire, margins erode. Now through 2014 represents the steepest drop-off of patent expiry in the history of the industry. While R&D processes have been, and will continue to be, streamlined, this can increase the pace at which new drugs are developed and approved - but this will still take time. Pharma has got to find contribution to the bottom line in parallel with R&D. This contribution can certainly be taking new approaches to managing and improving patient adherence rates. The challenge seems to be that the time it takes to validate an initiative has actually worked. While we have perfected the Volume 1 - Issue 1


Regulatory & Market Place

means to measure patient acquisition, the means to measure patient retention have not kept pace. A basic tenet of sales has always been that it takes more effort to retain a customer than to acquire a new one. Why have we, as an industry, decided to focus on the side of the equation that in any other industry takes more effort - it makes no sense. If this is truly just a matter of measurement, then let’s not be limited by measurement. Change the measurement. Develop new tools. Consider new milestones. Figure 3: Impact of industry pressure

So, the industry is finally in the midst of change - but change to what? In the short term, the impact will be negative. The short-term answers were in downsizing – in cutting costs. Most companies were caught off guard and just did what made sense to maintain margins into the next quarter or the next year. Companies are just now beginning to consider what the longer term opportunities can be, and what competencies are needed for the future. The focus is starting to be on the need of the www.JforPC.com

patient, but it is truly not there yet. Why can’t we simply remember George Merck’s quote: “We try never to forget that medicine is for the people. It is not for the profits. The profits follow, and if we have remembered that, they have never failed to appear.” The future is with the patient. As population demographics change there will be opportunity to support an older, chronically ill patient. There is the opportunity to speak to patients in ways that are culturally relevant, to help patients manage barriers to managing their health. The only way we will recognise this is to keep our focus on the needs of the patient, then the bottom line will follow. If we continue to only measure success in terms of outright sales of tablets, we will never see the real value we can bring to help patients adhere to their regimens. Nor will we be able, over the long haul, to capture some of that $US 250 billion that we seem to keep leaving behind. Now who can afford either one of those options? Dyan Bryson is the Managing Partner/ VP Patient Strategy & Outcomes for Inspired Health Strategies. Dyan has been consulting to the life sciences industry since 2006. She has been part of the industry for more than 25 years via positions on both manufacturer and service sides of the industry working with Ciba-GEIGY, Merck, PPSI/Parexel, Vox Medica. Email: dbryson@patientadherence.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 27


Behaviour Programmes

A Patient-Centric Approach to Adherence The Problem Pharmaceutical marketers face the complex undertaking of maintaining patient adherence with Rx medications — especially when a chronic disease plagues the patient. Such patients are constantly exposed to a deluge of information from every healthcare source. In addition, many such diseases present themselves later in life, after lifestyle routines have been established and are exceedingly tough to change. Not only are these patients told to take their medications, they are expected to maintain a treatment/lifestyle regimen that presents a staggering array of physical and emotional barriers to adherence: • Monitoring their disease • Exercising on a regular basis • Modifying their eating habits • Seeing their healthcare providers regularly • Being prepared for the consequences of their illness • Living with the prospect of possible life-altering complications The Apathy Trap Only the most motivated patients are truly successful in staying 100% compliant and persistent with their medical treatment regimen. For most patients, the self-management “task list” is completely overwhelming on its own, let alone the fact that they are supposed to also live “normal” lives – care for families, work, cook meals, travel, enjoy time with friends, etc. And for the spouse, parent or caregiver of a patient, the task is just as overwhelming – s/he needs to learn how to motivate, encourage, force and/or cajole a patient to do all the right things. For patients, the combined stress of trying to manage everything at once can frequently lead to the same end: denial and/or apathy that triggers non-adherence. The Solution For an adherence programme to be successful, it must incorporate a sensibility toward patients’ potential state of denial/apathy via direct-to-patient (DTP) relationship marketing. All communications must “interact” with patients accordingly. Simply providing educational materials and/or getting patients face-to-face with a healthcare professional will not work. One only has to look at the medical data of any patient population that receives only educational materials and provider intervention to confirm that the majority of these patients are not within the recommended control levels established by most major medical institutions. Even when faced with the dire consequences that are the result of improper self-management, many patients just don’t know how to do what they’re told to do. Trying to adopt different eating habits, exercise routines, medication regimens and testing patterns is a daunting task at best! Even if they can remember everything their healthcare provider tells them at each visit (and studies show that most patients forget 65% of all verbal information within five minutes), it is extremely difficult to customise this “generic” information to the patients’ specific lifestyle needs. Thus, in addition to taking into account and addressing this potential state of denial/apathy, a successful adherence 28 Journal For Patient Compliance Strategies to enhance Health Outcomes

programme must provide ongoing, customised information specific to each patient’s lifestyle, needs, wants and responsibilities beyond the medical condition. To be truly “patient-centric,” an effective pharmaceutical marketing programme must live with the patient – at home, at work, at play, and at the doctor’s office. It cannot only be attendance at a special event or receipt of a newsletter; it must integrate everything the patient does from “cradle to grave.” Implementing a Successful Programme There are two core elements to implementing a successful adherence programme that must be afforded equal emphasis: 1. Patient Acquisition 2. Patient Retention Patient Acquisition Critical to the success of an adherence programme are proper patient acquisition techniques. Such initiatives should ensure patients’ participation in the initiative and capture the initial data that allows for the first level of customisation and segmentation. This initial data will shape the follow-up materials/information. A properly designed patient acquisition effort will: • Maximise initial patient response • Allow  for measurement of different vehicles against the Allowable Acquisition Cost (AAC) •C  apture the necessary data to drive initial fulfilment and segmentation Stimulating Participation To offset the potential denial/apathy that can be a characteristic of people with a disease and get them to respond to an offer/request, adherence programmes must target patients at a time and place where they are most likely to be cognisant of their condition: •A  ctively searching for healthcare information • Purchasing healthcare supplies •E  xperiencing a disease-related event (e.g., poor test results, complication, hospitalisation, etc.) • Scheduling and/or participating in a medical appointment •P  articipating in a health-related activity (e.g., weight loss programmes) • Thinking of their healthcare needs • J oining a new healthcare plan/provider Even though patients are most cognisant of their condition when in the presence of their healthcare providers, it is critical not to expect healthcare providers to actively enroll patients in any type of programme, even if they are compensated for doing so. On the contrary, history has proven that enrolling patients through healthcare professionals does not work. Therefore, it is most important for the programme to focus on the patients themselves – the possibility of apathy and denial aside, patients are the ones who care most about their healthcare and have the greatest risk/ reward of participating in an adherence programme. Selecting Acquisition Vehicles The use of different acquisition vehicles will vary based on the Volume 1 - Issue 1


Behaviour Programmes regulations and resources available in each market (e.g., direct mail, e-mail, advertising, the web, partnerships, etc.), but they should always be based on two key criteria: 1. T  he patients’ relationship to the specific “capture points” identified as part of the planning process 2. A  dditional issues that are identified by research and/or consistent with the predefined programme criteria, such as geographic, demographic and psychographic conditions At the same time, an Allowable Acquisition Cost (AAC) is predetermined based on a patient’s projected first-year profit potential (at an average rate of compliance/persistency), minus the percentage of market share that the product/service already maintains. For example, if a patient’s first-year potential profit is $200, and the product already has a 40% market share, $120 of every patient purchase is going to the competitors’ products. As a result, the AAC to acquire 100% of a patient is $120 or less. Each acquisition vehicle used should be fully measurable. It should also be tested and evaluated on its ability to acquire patients at the best cost within the AAC. As different vehicles during the test phase are contrasted and compared, the performance metrics will determine which acquisition vehicles are used for rollout, and their costs/response rates can be predicted within a 90% confidence interval. The Importance of Customisation and Segmentation Can generic acquisition vehicles get people to respond to an initial offer/request? Definitely. Can generic acquisition vehicles get people to respond to ongoing offers/requests? Maybe. Can generic acquisition vehicles get people to take the actions necessary to be compliant with their treatment regimen? No. As part of the patient acquisition process, adherence programmes must capture the initial set of data that will be used to customise follow-up communication(s). This information typically includes the patients’ name, address, e-mail, phone (if necessary) and the data necessary to address each patients’ specific concerns/condition (e.g., newly diagnosed vs. long-term therapy, severity of condition, type of medication, presence of adverse events, etc.). As the patient begins to receive information addressed to her and specific to her needs, the perceived value of these communications increases – and so does her response. This initial data capture is also critical to start building the patient segmentation model because all patients are not alike. Not all patients are worth the same in terms of potential profit; and not all patients need the same frequency of follow-up to ensure an acceptable level of compliance and persistency. As a result, an effective segmentation model allows adherence programmes not only to create “best buyer” profiles, but also to model future initiatives based on their ability to predict the outcome of acquisition efforts defined in the test phase. Finally, since data capture has an adverse effect on response, it is important to recognise that acquisition efforts should capture only the initial data required to establish the first phase of customisation and segmentation – the more data asked of patients, the lower the response rate will be. As a result, customisation and segmentation models should be created in a “build” format, so information can continue to be gathered throughout the retention phase to further enhance the capabilities in these areas. 30 Journal For Patient Compliance Strategies to enhance Health Outcomes

Patient Retention Once patients respond to an initial offer/request, it cannot be assumed they will respond again or follow through on their anticipated behaviour (e.g., fill an Rx, attend a meeting, etc.). Everyone makes commitments that, at the time, are interesting and manageable. But when the time comes to follow through accordingly, and other issues have arisen and/or interest levels are no longer as high, people naturally exhibit non-compliant behaviour. A complementary patient retention initiative will: • Maximise compliance with the treatment regimen • Help ensure patients’ continued participation and response • Allow for the creation of “best buyer” profiles •C  apture valuable data to enhance segmentation and customisation efforts • Provide the necessary data to develop predictive models that will increase the efficiency of future adherence marketing efforts There are several critical elements needed to develop and implement successful adherence programmes across multiple therapeutic categories. The five key elements to improve patient adherence are: 1. Education 2. Self-management tools 3. Incentives 4. Patient/provider interaction 5. Family support When used in combination, and customised to the patients’ needs, these five elements will consistently improve patient adherence with the desired action (e.g., take medication, test as recommended, visit their healthcare professionals, etc.). These five elements, when combined, are effective across a broad range of chronic patient conditions, and can potentially exceed the programme objectives. Based on the predetermined segmentation model that defines the different patient types and corresponding frequency of communications, any patient retention programme should incorporate these five key elements to improve patient compliance: Education Education is critical to establish proper patient expectations. Proper expectations are one of the keys to improving patient adherence. If a patient expects fewer side-effects and/or a faster-acting product, and they experience more side-effects and/or slower efficacy, they are likely to discontinue product use immediately. While patients currently have access to a plethora of online and offline patient education materials that focus on disease management, the information is difficult to sift through and is not necessarily specific to the individual needs of any one patient. If a patient who has had a disease for 10 years has to first wade through information regarding disease identification, she will quickly get bored and uninterested. Self-Management Tools It is necessary to provide patients with more than just customised educational materials to drive adherence with a desired action and/or behaviour. An effective adherence programme must help patients convert this education to action. By providing patients with self-management tools, they will better understand how to Volume 1 - Issue 1


Behaviour Programmes best apply the information to make everyday changes in their lifestyles. Incentives Incentives help motivate patients to take the desired actions that will help them improve their disease self-management skills. Whether financial, informational, or educational, incentives increase patients’ likelihood of responding to and/or staying involved in the disease management programme. Patient/Provider Interaction Initiating and assisting patient/provider interaction adds credibility to the message and reinforces communication points. “Planned” interaction serves three purposes: 1. T  o capitalise on the “affinity” patients have with their providers to create the perception that adherence communications are part of their overall doctor/patient relationship 2. T  o increase physician awareness and education through patient-specific information and gain their “support” toward the adherence programme 3. T  o drive physician behaviour as a result of patient discussion and intervention (i.e., when a patient asks about certain products or tests, physicians are more likely to prescribe or order them specifically) Family Support Family support is critical to help patients modify their lifestyles. In a typical patient environment, lifestyle changes are most easily accepted if they are incorporated into the family routine. By better educating family members and providing them with the information and tools they need to assist in patient selfmanagement, the chances of improving patient adherence to lifestyle changes is increased (e.g., diet, exercise, testing, etc.). Communication Frequency The best results are achieved when these five key elements are incorporated into all communications on a frequent basis during the first three to four months of the programme (specific frequency of communications is driven by the segmentation model). By establishing proper patient habits during the initial months of therapy, the likelihood patients will modify their lifestyles and establish new behaviour patterns is increased. After this first fourmonth period, ongoing communication should be maintained, but can be provided less frequently. Also during the first four months, it is important to use these retention vehicles to capture additional patient data to further enhance the segmentation model. As the patient relationship develops, so does the patients’ willingness to provide additional information. Once patients see the positive results of providing additional information (through the receipt of customised information specific to their personal needs), and are assured of its confidentiality, they will provide almost any type of information requested. As a result, adherence efforts should include segmentation models and communication strategies that can be “built” over time, concurrent with the development of the patient relationships. Communication Channels It is also critical for adherence programmes to consider “how” information is delivered to patients. In today’s digital www.JforPC.com

environment, one must communicate with patients across all available channels. Determine the way patients want to communicate with you as they move through the multiple communication channels that are available to them – any time, any place, anywhere: 24/7. Engage, transact, service, and support customers accordingly, by ensuring that the right people get the right message, in the right place, at the right time, with the right offer. Gain their permission and trust. Tailor your people, processes and technology to respond to your customers’ changing needs in real time. Patients want to communicate via different vehicles at different times. While some are more comfortable using one communication/information media (e.g., direct mail vs. e-mail), more and more patients are interested in communicating across digital channels. In fact, the “senior” population is now the fastest growing segment on the web and represents a majority of the online “health information seekers.” At the same time, this target audience is still very receptive to direct mail and other “offline” media. As a result, a media mix across all channels should be considered for patient acquisition and retention efforts in any adherence programme. Messaging Format Finally, regardless of the channel in which the message is delivered, adherence programmes should package information in small, easy-to-understand “soundbites” to increase the level of patient comprehension and uptake. The format should be adapted to take advantage of the dynamics of each media (e.g., web vs. mail vs. phone, etc.), incorporating quick, easyto-understand messages. It is also important to use the available patient data to customise the messages specifically to the patients’ interests and needs. Simple, frequent, visual, customised messages have the greatest impact in modifying patient behaviour and improving compliance. Conclusion To be truly successful, adherence programmes must include a patient-centric approach to communications – concentrating on patient acquisition and retention efforts to maximise adherence and Rxs. The programme must address the patient’s potential toward apathy and denial. While patients may respond to an initial request/offer, there is no guarantee that they will continue to respond or remain adherent with their treatment regimens. As a result, it is imperative to develop an adherence programme that incorporates an awareness of the patients’ potential state of denial/apathy and provides ongoing, customised information specific to each patient’s lifestyle, needs, wants and responsibilities beyond the medical condition. To be truly “patient-centric,” an effective pharmaceutical marketing programme must integrate everything the patient does from “cradle to grave.” Jay H. Bolling is the President/CEO of Roska Healthcare Advertising. Jay is a recognized thought leader and innovator among today’s pharmaceutical and medical device marketers. Jay is the Past President of the Healthcare Communication & Marketing Association (HCMA) Email: jbolling@RoskaHealthcare.com Journal For Patient Compliance Strategies to enhance Health Outcomes 31


Behaviour Programmes

Compliance: the Greatest Enemy of Cure Compliance or adherence is one the biggest problems in healthcare. With so many researches, discussions, meetings and articles about this issue, it needs a new, fine, intelligent and fresh perspective to add something. Advice from the journalist of the traditional Dutch paper, the Financial Daily: make a statement in the beginning. My statement; don’t let any healthcare professional indicate what to do about the problem of compliance. Compliance is a problem that has to be solved by medication users and their families / partners, commercial business and social media. Definitions to distinguish: 1. I t’s medication users; each and every person is a patient (from birth till death), or patient is used only when people are clients in active involvement. 2. P  artners, from lovers to buddies, are as important as medication users themselves. 3. B  usiness is familiar with daily life circumstances and commercial business knows the freedom of choice, client needs and self-supply. 4. M  ost information about human behaviour can be found within social media. The Position of Healthcare in Compliance Healthcare and Health Professionals are Needed When they are Needed. Statistical Facts Statistics from the Central Office of Registration (CBS in the Netherlands) show that constant involvement of healthcare only happens in 0.2% of human life. Involvement as in control, availability and treatment accounts for 5% of a lifetime; 20% of the peope are using direct communication with healthcare professionals. Common Facts Everybody fears visiting a doctor. There is fear of giving up one’s normal life and being captured by the rules of health. Denying the fact that health problems restrict your mobility through pain, discomfort or loss of physical, neurological or psychic functionalities is better than losing your freedom and mobility by health treatment. Social Facts The goal of health treatment is to cure, so people can go home and live their own lives. The more treatment, the less normal life, and the more commitment of healthcare, the less commitment of family, partners, children, colleagues, neighbours and so on. People prefer their other roles, like being a client, employee or parent, above the role of patient. Medical Facts Medication is one of the best methods to ensure that people can take care of themselves and avoid as much as possible treatement by human beings. Self-care for each regular medicine 32 Journal For Patient Compliance Strategies to enhance Health Outcomes

user takes in general more than 90% of a day. Whatever is needed (statistics), whenever forced (common facts), however incorporated into life (social facts), professional treatment is less than 80%. Medication Users seen as Human Beings? People don’t want to be patients, don’t want to adapt their lives to the rules of regularity and care, and don’t want to arrange everything as ordered. I am sure that people reading this will think or say: but patients have to be aware of the fact that they are sick and will get into trouble if they don’t take their medication in the right way, as well as trusting that the professionals know about health and medication. All conferences about compliance I have joined, all discussions I have commented on, and all researches and professional articles I have read include at some point the remark that patients forget, that patients are not aware of their position and that patients sometimes even consciously refuse to take their medication or treatment regularly, or even at all. From this point, they take over from the professionals, dictating the way compliance should be approached. Self-care, self-management and the responsibility of patients will be acknowledged, but health profesionals know best. Patients forget, or are not aware, and bring themselves into danger. I am such a Patient; a Regular User of Medication. My comment when I notice this powerplay: beeeeeeeeep... Healthcare providers - back off and do the things you can and need to, when requested. Professionals - you are hired and paid by your clients. Even when regular users are patients - professionals, you are their servants. When people ask you, you care, but self-care is something completely different. Practioners - you are paid to do the things you know at the moment you are in touch with them, and after that moment you can’t do anything and you know nothing. You are frustrated; users fail, forget, give up and then in despair you make these feelings professional and give it a scientific touch. But shouting, offending, making users ridiculous, calling them “slobby swallowers” as if they are cartoon characters is far from serious commitment. The care attitude tends to shift to something intangible as if care is something sacred. Healthcare presents failing users as disobedient patients; desperate users as victims to be protected against commercial sharks; searching users as laymen in danger; and experienced users with their partners as dangerous. Who Cares? Healthcare professionals are seen as experts, as coaches, as providers, as places to stay close to, as guards, as inspectors, as designers of devices, as dictators of a regular life. Who is responsible for obtaining the basic conditions to give medicinal treatment a chance to succeed? Let’s describe the chain. People with health complaints get sick and go to health practitioners. These professionals diagnose. Volume 1 - Issue 1


Behaviour Programmes

Some health problems can be treated with medication and professionals arrange the right medication, the right regularity and how much. After that, people have to do it on their own, no matter what their health problem. First difference to usual perspectives: there is no focus on disease characteristics, but on characteristics of managing medication after 1. visit, 2. diagnosis, 3. prescription. Second difference in perspective: for about 20% of a human lifetime, people become patients, and only 0.2% of lifetime healthcare consists of 100% involvement. Patients united in patient groups, or those who get close to this 100% dependence, are an extremely small minority. Compliance, however, is focussed 100% to this minority. Severe patients with more than 50% self-care use clinical care solutions. Diabetics; people with cardiac problems, Parkinson’s, ADHD and hay fever; and people using contraceptives live a normal life in general and are the largest groups of users. There is no support for their circumstances whatsoever. Third difference in perspective: what does healthcare know about daily life, about abnormal distractions, about forgetting, about frustration, about fear, about healthy behaviour, about hope, ambition, mobility, love, disasters and dramas in a chronic life with medication? Does healthcare know how to take medication if your newborn sons are in mortal danger? How can you take medication without sitting next to the clock nine times a day, every day, for the rest of your life? How do chronic users take medicines while driving a car, several times a year? Being a mother or father; is it possible to plan your life around the moments of use? Having a job with meetings and presentations; what choice do you have with regard to focusing on medication or the importance of your company? How do you keep your love life healthy when faced each day with remarks like “did you take your medication”? What about an epileptic, or a youngster who is ashamed about his obvious pillbox in front of his classmates? The end of operative pill-time means upcoming health problems, and they push away the clear mind to remember. What a shame, what a stress, being alert all day, each day, for the rest of your life. The stigma, the planning, your family as co-patients, the irregularity and chaos appearing each day from unexpected angles and at unexpected moments. The blame you get from health professionals, the costs to society your failures cause, new treatments and new schedules and new frustrations, longer-term patient care, adapting your life and feeling even more blocked by this than your health problems. www.JforPC.com

Compliance; Who Knows? Crowdsourcing from Wool Lab proved what makes sense: medication users know; their partners know; information about health problems is easy to find and users are trustworthy - it’s their life. Businesses know; they also have the knowledge to design cars, washing machines, bikes, heaters, educational programmes and food and homes. But no; healthcare professionals don’t see “medication users as human beings”. Healthcare knows about a very small minority, and the majority has to struggle, to adapt, to remember properly, to obey, and if not they are doomed to let healthcare more and more dictate their daily lives. Those numerous regular users will lose jobs, hobbies, love life, business, ambition and so much more. But if they refuse to give up this freedom, they can be called “slobby swallowers” or blamed as if it is their own fault for not adapting. They are criminals because consciously they stop medication. Healthcare knows, because it knows diagnoses and medication. Healthcare knows that 100% compliance is the minimum to get a chance of success. Healthcare thinks it knows how to become compliant If all the efforts, the support, the (wrong) expertise, the research and discussions and conferences, the claims, the (unavailable) time / money / research, and the exclusion of everything and everybody that knows better or more, is not enough to get even close to 100% compliance. Who is responsible then for the damage done? Healthcare blames business, patients, partners and the mafia (some serious health professional stated in a LinkedIn discussion that businesses who offer their services to facebook are supported by the mafia). Compliance directed by healthcare is responsible for damage to the economy, for lost lives, and for the health of billions, if acting this way. Pillkey® is a consumer business from a medication-user, supported by non-healthcare professionals using social networks, the internet and daily life design to achieve what healthcare can’t; 100% compliance for chronic users. It also brings more safety, security and freedom of use, and more effective communication to healthcare when needed, with less alertness, less shame, less guilt, better relationships, more time for family, children and friends, and less problems with unexpected circumstances. Be proud of your device and tell your classmates you are epileptic; pills are made to be the keys. It is possible to be 100% compliant, and if healthcare still claims more research, design and study to improve no more than 5% compliance for the minority, then is compliance the greatest enemy of cure by medication? Thom de Bruijn, 57 years: BuilderInnovator. Business: Cultivating, combining and recreating existing realities, in order to change unhealthy circumstances. Experience-expert in compliance and designer of the Pillkey® Medication Manager; digital assistant to take care of regular use in daily life. Email: tdb@pillkey.net Journal For Patient Compliance Strategies to enhance Health Outcomes 33


Clinical Trials

Addressing the Patient Factor in ePRO to Improve Compliance Patient-reported outcomes (PROs) are commonly used by biopharmaceutical companies to support regulatory filings, formulary submissions, and product marketing. Sponsors of PRO research have learned that patient compliance is dramatically improved when data is collected electronically from patients rather than by paper. Electronic patient-reported-outcomes (ePRO) compliance rates, however, can also be improved if Sponsors understand the reasons for non-compliance and patient preferences for PRO data collection. This article reviews the literature on patient compliance relating to ePRO and summarises recent research conducted with patients to provide a broad picture of how Sponsors can improve patient compliance during trials involving PRO. ePRO in Clinical Trials PROs are often used in clinical trials to measure treatment efficacy and endpoints. Unlike laboratory tests and other physical assessments that require interpretation from a secondary source such as a clinician, PROs are measures that come directly from patients. Hence, PROs provide a unique window into how patients perceive the investigational drug and the state of their health during treatment. As PROs are essential data points in many clinical trials, obtaining high levels of patient compliance is extremely important to the success of studies. Evidence shows that higher compliance can be achieved if data is collected by electronic means rather than paper.1,2 Higher compliance with ePRO is directly related to special features that electronic technologies provide, such as reminders for patients to complete diary entries, mechanisms to facilitate data completion (e.g., not allowing patients to skip questions), alerts to investigators and the study team of non-compliance, and time-stamped data that assures diary entries were made in a timely manner. As a result of such electronic facilitators, the quality of patient data is greatly enhanced over traditional paper-based methods. Since ePRO allows for efficient data collection globally and high rates of compliance, it is extremely important that Sponsors, investigators, and key study personnel play roles in assuring that ePRO systems and procedures are convenient and user-friendly for patients. This article will help Sponsors along those lines by providing a literature review on patient compliance in trials involving ePRO and contributing proprietary Almac research data collected via surveys and interviews. Addressing the Patient Factor in ePRO Compliance While ePRO helps to improve compliance, it cannot force patients to consistently comply. Patients are people, after all, and can choose whether or not to adhere to study protocols. Hence, when designing and implementing ePRO systems, Sponsors need to understand why patients are not compliant and make use of technology features that encourage patients to stay active in the study. By doing so, Sponsors will improve compliance and the overall quality of trial data. 34 Journal For Patient Compliance Strategies to enhance Health Outcomes

To provide insight on patient compliance in ePRO, the authors conducted a literature review of 132 articles (published 19952011) that reported on the results of studies utilising ePRO. From that literature review, we identified and analyzed 25 articles that focused on reasons for non-compliance and 20 that reported on patient preferences (in comparing paper to ePRO).3,4 Lessons learned from the literature were combined with insights collected directly from patients through blinded proprietary research sponsored by Almac. The study was conducted to better understand the challenges patients face when participating in trials involving ePRO. Subject inclusion criteria consisted of having been enrolled in at least one clinical trial within the past two years in which keeping a diary was required. In total, 307 patients responded to a 10-minute internet based survey that contained both quantitative and qualitative questions. Additionally, 10 patients were interviewed to provide qualitative insights. Respondents were based in the United States and the gender of the sample was generally balanced (55% female and 45% male). Females had previously participated in an average of four clinical trials with diaries and males in an average of three studies. Patient Compliance Rates Almac’s patient survey revealed compliance with diary completion during clinical trial participation was very high (96%). Since this number was reported by patients themselves, it is possibly inflated due to overly positive self-reporting. By contrast, the average ePRO compliance rate overall in the literature review was lower (86%), yet still moderately high when compared to paper collection (79%).4 It is important to recognise that compliance varies among studies due to several factors, including the nature of the illness, patient population, study design, and patient experiences, among others. Ultimately, even if it seems impossible, researchers should strive to achieve 100% compliance to obtain full representation of the study population by attempting to prevent non-compliance whenever possible. Addressing Reasons for Patient Non-Compliance Uncovering reasons why patients are not compliant leads to identifying ways that ePRO systems and study designs can improve compliance. Ten major reasons for non-compliance were identified in the literature review. Listed in order by highest frequency, they include3: 1. Time 2. Reminder issues 3. System issues 4. Personal reasons 5. Health 6. Equipment loss 7. Study design 8. No/limited access to input data 9. Length of study 10. Other. Volume 1 - Issue 1


Clinical Trials As time to complete diaries is the top reason for non-compliance, it can be concluded that burden is likely a major underlying cause of non-compliance. The survey further supports this explanation as 58% of patients indicated that shorter diaries are associated with more favourable diary experiences. Hence, study designs and protocols should be sensitive to the amount of time required by patients to complete diaries – choose shorter diaries where possible, check with the diary author to see if an appropriate short form is available, limit frequency of required diary completion, and reduce frequency of lengthy questionnaires whenever possible. To address another important reason for non-compliance (system issues), Sponsors and vendors should develop glitch-free technologies that are reliable and user-friendly, as this will likely reduce patient burden and frustration. Moreover, since personal reasons (e.g., going to bed early, technophobia, confidentiality concerns, major life change, being on vacation, and lack of interest) are main factors contributing to non-compliance, it is important to make it as easy and convenient as possible for patients to complete their entries. On this theme, Almac’s survey research indicates that 59% of patients prefer to have multiple data collection modalities (e.g., phone, web, handheld device) that provide flexibility and convenience for completing diaries. However, it is important to note that use of multiple modalities should only be employed in trials where it is appropriate and feasible both clinically and in a regulatory sense. Given that reminder issues were identified as a main reason for non-compliance in the literature review, one way to improve compliance involves providing patients with effective reminders to complete their diaries. The key insights identified relating to reminders included: no reminders were provided, phone call reminders were not received, and current reminders were not sufficient. To better understand these challenges, Almac’s survey asked patients to identify what kind of reminders they wished to receive and how they preferred to receive them. The two top items for which patients wanted reminders were “anything they

36 Journal For Patient Compliance Strategies to enhance Health Outcomes

should take action on as part of the clinical trial” (76%) and “when they needed to record their ePRO entries,” (60%). In terms of mode of reminder, the majority of patients preferred email (80%) or a SMS/text message (55%). Compensation is often thought to be associated with increased patient adherence to PRO requirements. Within the literature review it was found that compensating patients did not impact compliance; however training them was associated with higher rates of compliance5. Additionally, in the Almac survey, when patients were asked why they would consider dropping out of a diary study, a main reason was having difficulty in understanding directions. These results indicate that providing patients with proper training and guidance allows for higher comfort levels in the use of ePRO systems, thus alleviating frustration and burden. Furthermore, when patients are trained, they require less support throughout the duration of the study. Therefore, Sponsors should plan to include patient training in the start-up phase of the trial and work with ePRO vendors to create effective training tools for patients and sites. Patient Preferences in ePRO In addition to identifying reasons for non-compliance, learning what patients like about ePRO may also lead to identifying ways to increase adherence to protocols. In the patient survey, the top responses reported for positive patient diary experiences were ease of use (66%), simplicity of questions (60%), and reducing the time spent to make daily entries (58%). In the literature review on patient preferences, the most common positive aspect identified was ease of use. Thus, anything Sponsors can do to reduce time and improve the user experience is essential. As indicated in the patient survey, such things would include providing multiple electronic technology options where appropriate (e.g. phone, web, handheld devices), offering frequent reminders, and making diaries easy to complete. Patient views of the negative aspects of ePRO, while reported less than positive aspects, are just as valuable, if not more so,

Volume 1 - Issue 1


Clinical Trials because they may directly relate to reasons for non-compliance. In the survey, almost half of the participants (48%) did not report any unfavourable diary aspects. But for those who did offer responses, the most common were: entries were too frequent, lack of multiple data entry options, and inconvenience. In the literature review focusing on preferences, most of the negative aspects that contributed to non-compliance were related to the development and design of ePRO systems.3 Patient Recommendations for Improvement Insights generated from Almac’s patient survey reveal other ways to improve compliance. To seek out suggestions from patients on how Sponsors can improve the diary collection process, patients were asked to report three of the most important things that can be done to improve their experience with ePRO. The patients’ suggestions were (ordered by highest response): 1. Provide multiple technology options for completing diaries (59%) 2. Shorten the time needed to make an entry (58%) 3. Make it easier to make an entry (54%) 4. Provide automated reminders (54%) 5. Provide an easy way to get help with making entries/directions when needed (42%) 6. Provide better instructions for making entries (30%). Patients were also asked to report the single most important thing that would improve their experience participating in a clinical trial involving ePRO. The most common themes represented in their open-ended responses were ease of use, reminders, and convenience and clarity of what is expected of them relating to study procedures. Summary and Conclusions Since high levels of patient compliance are critical to successfully collecting and analysing PRO data, Sponsors of clinical trials must understand the reasons for non-compliance and take actions to address them. This article points out that understanding Table 1: Patient Factor Recommendations to Improve ePRO Compliance Patient Factor

Recommendations

Time

4U  se short instruments (when possible) 4 Require low frequency of administration (if appropriate)

Burden

4 Try to limit the burden on patients – ask necessary questions in an efficient way

Frustration / Ease of Use

4 Try to prevent patient frustration through making systems simple, straightforward, and easy to use

System Issues

4 Develop high quality systems supported by Help Desk assistance

Convenience

4 Provide ePRO options that make it convenient for patients to respond, such as internet and email 4 Offer multiple technology options and flexibility where possible, feasible, and appropriate

Reminders

4R  emind patients to complete ePRO tasks 4E  nsure patients are equipped to receive reminders 4 Allow patients to select their preferred reminder type (e.g., email, text message)

Training

4 Train patients to use ePRO technology at the start-up phase of the trial 4 Provide patient with clear instructions

Support

4 Provide patients with a help/user guide, web site support, and help desk

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patient preferences for technologies and improving the patient’s experience with keeping a diary is essential to driving higher compliance rates. Throughout this investigation into the factors affecting compliance, several common challenges facing patients came to light. These are summarised along with recommendations on how to address them in Table 1. References 1. Stone, A.A., Shiffman, S., Schwartz, J.E., Broderick, J.E. & Hufford, M.R. Patient non-compliance with paper diaries. BMJ. 324(7347), 1193-4. (2002). 2. Gwaltney, C.J., Shields, A.L. & Shiffman, S. Equivalence of electronic & paper-and-pencil administration of patientreported outcome measures: a meta-analytic review. Value in Health. 11(2), 322-323. (2008). 3. O’Gorman, H., Ross, J, Peck, R & Ross, E. Identifying Patients’ Reasons for Non-Compliance in ePRO studies to Improve Data Collection Methods. Presented at DIA 23rd Annual EuroMeeting, Geneva, Switzerland, March 2011, http://www.diahome.org/diahome/ FlagshipMeetings/home.aspx?meetingid=23313&utm_ source=DIAHomePageGlobal&utm_medium=Banner&utm_ campaign=11101 (2011). 4. Ross, J., O’Gorman, H., Peck, R & Ross, E. Electronic versus Paper data collection of Patient Reported Outcomes: What do the Patients Think? Abstract accepted for poster presentation at the DIA 47th Annual Meeting, Chicago, IL June 19-23, 2011, http://www.diahome.org/diahome/ FlagshipMeetings/home.aspx?meetingid=23753&utm_ source=DIAHomePageGlobal&utm_medium=Banner&utm_ campaign=11001. (2011). 5. Ross, J., O’Gorman, H., Ross, E & Peck, R. Take Time to Train: Evidence to show that Patient Training in Electronic Patient Reported Outcomes is Beneficial. Abstract accepted for poster presentation at the ISPOR 16th Annual International Meeting, Baltimore, MD, May 21-25, 2011, http://www.ispor.org/Events/ Index.aspx?eventId=35 (2011). Jennifer Ross is currently a Senior Biostatistician at Almac Clinical Technologies, a company which provides technology, patient and drug supply management, as well as ePRO services to the biopharmaceutical industry. Prior to joining Almac, Ms. Ross spent six years as a clinical research professional at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center. Ms. Ross has earned two Statistics/Psychometrics Masters degrees from the University of Pennsylvania, where she has taught graduate level statistics in recent years. Email: Jennifer.Ross@almacgroup.com Hannah O’Gorman is currently the ePRO Product Manager at Almac Clinical Technologies. Ms. O’Gorman has been working in the Pharmaceutical industry for 10 years, focusing mainly on ePRO and other clinical technologies. She is a member of several professional associations and has presented at a number of industry conferences including ISPOR and DIA. Email: Hannah.OGorman@almacgroup.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 37


Clinical Trials

Factors that Influence Patient Compliance for Observational Studies Observational studies all begin with a blueprint. These initial plans invariably include clear objectives, liberal patient eligibility criteria and easily quantifiable endpoints. With proper discipline, the resulting study design will feature a simple method for collecting data, as well as an effective approach for ensuring that the critical patient-physician/medical care interface reflects the “real world” of post-approval clinical care. The study design should avoid any limitations on dosing or treatment options that would be more appropriate for a pre-approval clinical trial. By mimicking natural patterns of therapy, such designs also create conditions whereby patient compliance with the study procedures is high, since the participants see involvement with the project as a logical extension of their treatment. Without such discipline, study designs grow increasingly complicated, move steadily away from standard of care and ultimately offer patients few reasons to participate. Inadequately planned observational study designs experience poor patient compliance and lack credibility, which creates the inability to obtain balanced patient participation and limits one of the major goals for observational research: to gather information that is truly representative. The objective of this article is to identify the most important elements of observational studies that influence patient compliance, not in terms to adherence of a prescribed diet or treatment, but whether the patient remains an active participant in the project. Although there are hundreds of reasons why patient compliance deteriorates over time with certain observational study designs, a number of factors are consistently associated with projects that fail to reach their potential: • Placing unnecessary demands on patients • Attempting to collect too much, or the wrong kind of, data • Failing to create a sense of communal participation among patients and physician investigators • Ignoring the realities of how care is administered in the real world While the focus of this article is on patient compliance in observational studies, it is important to include the role the physician investigators play in ensuring continued participation. This is particularly important for observational studies, since many projects often last several years or even a decade. If physicians and their staff are burdened with excessive requirements for data collection and entry, or question the value of the study, they will fail to provide encouragement to their patients to continue with the project, and compliance will eventually deteriorate. Choosing the Right Method for Data Collection: patients are generally willing to participate in observational studies and complete outcomes-related questionnaires, unless the amount of information to be collected is onerous or the mode of collection represents a significant imposition. Approaches for collection of patient-reported outcomes or PROs typically 38 Journal For Patient Compliance Strategies to enhance Health Outcomes

involve one of four methods: i) use of patient diaries, ii) use of an interactive voice response or IVR system via the telephone, iii) use of the internet and a dedicated website or iv) collection of information in the physician’s waiting room (see Figure 1). Of the four approaches, diaries are widely employed for observational studies, although in practice most entries are made shortly before the transfer of information to the sites rather than consistently throughout the period of observation. Web-based approaches have also been frequently used for observational research, but such use implies a familiarity with technology that might not apply to all patient populations, particularly seniors. While IVR is regularly employed for preapproval clinical trials it can be challenging for patients participating in observational studies since phone-based approaches are often seen as intrusive. Moreover, given the naturalistic design of observational studies and the less rigorous interactions that exist between patients and physician investigators for such projects compared to clinical trials, any technological challenges that occur with web-based or telephone systems are difficult to resolve and can reduce patient compliance. Observational studies work best when the procedures employed mimic standard clinical practice. Thus, the most widely accepted approach for reliably obtaining information from patients is to collect data when the patients return to the physician’s office for regularly scheduled or ad hoc appointments. The time patients spend waiting to see their physician represents an excellent opportunity for them to complete questionnaires electronically or via paper. If the latter approach is taken, the information can be entered into the database by the physician’s staff for the patients. Figure 1: Commonly employed approaches to collecting information from patients participating in observational studies

Choosing the Right Data to Collect: all successful observational studies begin by identifying a tangible goal and working backwards to determine what type of data should be collected to achieve the desired result, as well as how much data will be required to meet the needs of the study. These decisions will influence the burden the study places on physician investigators, Volume 1 - Issue 1


Clinical Trials their staff and their patients, and therefore the willingness of these individuals to comply with the requirements of the project. As an example, below are two approaches to collecting data for an observational study involving patients with Alzheimer’s disease, one involving patients living in the community and the other involving patients residing in long-term care facilities. Approach No. 1 – Collecting data for Alzheimer’s patients living in the community: a traditional clinical trial focuses on a product’s efficacy and safety, and rigorously mandates the type of data investigational sites collect to assess these parameters, as well as the frequency with which such assessments were made. In contrast, an observational study design seeks to mirror standard approaches to managing patients in order to make an overall assessment of the product’s “effectiveness”. For Alzheimer’s patients, the latter design would seek to collect information regarding clinical outcomes such as cognition, but also information regarding economic outcomes such as the cost of care and changes in the use of concomitant medications, and humanistic outcomes such as the level of functional activity for the patients, and the quality of life for care-givers. Moreover, the data would generally be collected by the physician investigator or their staff using an electronic data capture (EDC) system designed to mimic the way data is routinely gathered and entered in standard medical practice. Efforts to go beyond collection of the standard assessments noted above, or to impose a cumbersome data capture system that added significantly to the time normally required to collect and enter patient information, would invariably limit the quantity and quality of the data collected. Approach No. 2 – Collecting data for Alzheimer’s patients residing in long-term care facilities: conducting research involving patients in assisted-living or other long-term care settings can be complicated, given that medical care can be provided by either the patient’s own physician, a variety of specialists including individuals who treat patients suffering from dementia, or a medical director who serves the collective needs of the facility. However, most countries regulate the care of elderly patients and institute uniform approaches regarding the type of data that must be collected regarding the patients’ conditions and how their treatment is being managed and monitored. Thus, a voluminous amount of data is routinely collected for such patients, and in a manner that is relatively easy to obtain and evaluate. In the United States, the federal government mandates that the health of long-term care residents be monitored using a tool referred to as the Minimum Data Set (MDS), which collects clinical information on a quarterly basis regarding cognitive patterns, quality of life, activities of daily living, medication use, treatments and procedures etc. While the use of traditional approaches to evaluate Alzheimer’s patients such as Mini-Mental Status Examination (MMSE), standard care-giver assessment questionnaires, etc., are generally not part of the standard of care for the institutionalised patient population, other approaches are readily available to collect the data required to make reliable assessments of their condition. Indeed, elements of the MDS have been validated, such as the cognitive performance score and have previously been employed to characterise patient performance in clinical studies. Maximising Participation of Patients and Sites: maintaining 40 Journal For Patient Compliance Strategies to enhance Health Outcomes

a high level of engagement with physician investigators and patients throughout the duration of a lengthy observational study is critical and requires a carefully considered and focused approach. Given the close relationship between such engagement and compliance, a number of useful approaches (described below) have been developed to enhance the shared sense of community that is essential to successful observational studies. Establishment of a scientific advisory board consisting of thought leaders and representative practitioners. Working with a well-constructed advisory board represents an excellent approach to i) obtain useful insights regarding proposed study designs, ii) provide encouragement and/or inspiration to participating sites throughout the course of the study, through the use of newsletters or regional symposia and iii) gather support for developing manuscripts and publishing the study results. Statements from members of the advisory board regarding the benefits of study participation, such as obtaining a better understanding of the underlying etiology of particular conditions and developing better approaches to treating those conditions, can foster a spirit of esprit de corps and help create a clear and compelling rationale for sites and patients to join the project. Branding: observational studies, particularly those involving a competitive indication, benefit from a clear, recognisable and memorable visual identity applied consistently to all study-related materials. Study branding typically consists of a combination of translatable headlines, colours, graphics and/ or images teamed with a memorable logo which together will create the visual platform. For patients, the study brand is designed to attract and inform while demonstrating empathy with their medical condition and introducing the study to them in a non-coercive manner. While branding can be helpful for fostering a sense of community among sites and patients, it is important that such an approach does not introduce bias or inappropriately influence patients’ thinking. Benchmark reporting to physicians: an additional method Volume 1 - Issue 1


Clinical Trials

for achieving engagement with investigational sites is the use of benchmark reporting to physicians. Observational studies often include a large percentage of research-naïve physicians who value the opportunity to contrast their experience with that of other practitioners. Importantly, such benchmark reporting may provide useful insights into the optimal uses of new products and/or of the characteristics in general that can be associated with optimal outcomes and “best practices.” Addressing the Realities of “Real World” Health Care Administration: the standard concept of a single site enrolling patients for a clinical trial and managing all components of their treatment does not always match the “real world” complexities of healthcare administration. For many conditions, patient care represents a complicated amalgam that begins with a primary care physician, but may also include the involvement of a surgeon, a short- or long-term rehabilitation centre, an infusion clinic and/or a wide variety of other healthcare providers. When country-to-country variations are included, the matrix of treatment options becomes even more complicated. While such differences can be addressed for pre-approval clinical trials by including only those sites where approaches to clinical care can be tightly controlled, such options are not appropriate for an observational study in which the objective is to obtain a “representative” assessment of clinical care. In addition to understanding how the different components of the healthcare system act in an integrated manner for complex real world studies, one of the keys to successful management of such projects is to determine which of the different physicians treating the patient should engage with them to discuss the study objectives and obtain informed consent. If the incorrect decision is made the likelihood exists that only a small number of patients will agree to participate in the study and their compliance with any study-related procedures will quickly begin to erode. A second critical component is to employ an operational strategy that will ensure effective engagement with each of the diverse components. Use of a traditional on-site www.JforPC.com

monitoring approach in which a clinical research associate (CRA) is dispatched once every six-to-eight weeks will be expensive and also cumbersome, since each “site” will have multiple components, each of which will require some form of interaction. An alternative approach is to limit on-site monitoring to an annual visit for face-to-face interactions with the various investigators and their staff and instead engage with the different components remotely via phone on a monthly basis, or more often if required. Such frequent and sustained interactions, particularly during the early stages of complex real world studies, allow the operational team to identify the individual needs of each “site” and develop customised approaches that ensure patients, physician investigators and staff all remain compliant with the study requirements. The success of any prospective observational study is judged by its ability to collect representative data in as noninterventional a manner as possible, from which implications can be credibly derived regarding the incidence of a particular condition, the manner by which the condition is treated in a real world clinical setting, and the outcomes of different approaches to treatment. While attention is generally focused on the type of data gathered, including medical utilisation costs, patient-reported outcomes and the incidence of safety-related events, and the manner by which the information is obtained, data collection is ultimately dependent on the participation of patients and their willingness to remain in the study. Given the long duration of many observational research projects it is important to understand the factors that influence patient compliance for these studies to ensure that data collection will be robust and meaningful. For more information about PharmaNet Development Group’s comprehensive range of services, please contact Anne-Marie Hess at ahess@pharmanet. com or visit www.pharmanet.com. About PharmaNet Development Group, Inc. PharmaNet Development Group, a recognised leader of global drug development services to the pharmaceutical, biotechnology, generic drug, and medical device industries, provides comprehensive capabilities in Phase I-IV clinical development, bioanalytical and bioequivalence services, regulatory, staffing, and therapeutic solutions. For the applied knowledge and intelligent solutions needed to accelerate drug development programmes of all sizes around the world, PharmaNet works for you. Dr. Ronald E. Weishaar is Executive Director, Observational Research, for PharmaNet’s Phase IV Development Group. Dr. Weishaar has global responsibility for the design and implementation of noninterventional studies, and has extensive experience with safety registries, efforts to evaluate standard of care for different conditions, and studies with combined clinical/scientific and commercial/strategic objectives. He has also coordinated Phase IV projects involving at-risk patient populations, with a particular emphasis on research in seniors. He holds a BS and MA in Chemistry, and a PhD in Pharmacology, and has held previous positions with the Huntington Institute, ParkeDavis, and Coromed/Omnicare Clinical Research. Email: rweishaar@pharmanet.com. Journal For Patient Compliance Strategies to enhance Health Outcomes 41


Clinical Trials

Using Mobile Phone-Based Technologies for Improved Patient Recruitment, Retention, Compliance and Data Reporting in Clinical Trials Patient retention and compliance are critical components in the success of clinical studies. Through a lack of planning, the risk of patient drop-out is extremely high and will only increase as trials become more complex and lengthy. Statistically, over 85% of clinical trials fail to retain enough patients, with the typical patient drop-out rate across all clinical trials being 30%. Of 50,000 clinical trials in the US alone, 80% were delayed by one month or more due to unfulfilled enrolment. Depending on the therapeutic area, patient discontinuation rates can be as high as 40%, with the process of replacing lost patients impacting significantly on the cost and timeline of studies, in addition to decreasing data quality. Without supportive reminders, patients are likely to forget medication regimens, clinic visits, fasting procedures, blood draw preparation and diary reporting. This lack of patient support can often culminate in poor quality and accuracy of trial data. At the same time, regulatory standards governing methods of data collection and evaluation in clinical trials have become increasingly stringent. It is mandatory to implement methods that are deemed as suitable for use in clinical research, in accordance with the regulatory requirements of FDA 21 CFR part 11, US Healthcare Insurance Portability and Accountability Act of 1996 (HIPAA) and the EU Directive 2002/58/EC (Directive on Privacy and Electronic Communication). These regulations require that all data is encrypted to 256 bits and stored on a secure database, patient consent is obtained before communication begins, and there is a simple ‘opt-out’ service for patients or sites. Additionally, full message tracking capabilities are mandated to generate delivery reports, guaranteeing the surety of receiving the messages, and providing a full audit trail for regulatory submissions. It is with this background that mobile phone-based communication technology has been introduced to address these challenges and improve patient retention and compliance, all while complying with regulatory standards. This article discusses the latest advances in mobile phone-based communication technology and demonstrates its benefits for patient retention and compliance through a real-life application.

Ultimately, many good quality volunteers and patients simply never find out about clinical trial opportunities. As a result, consumer advertising and direct subject contact emerged as the most effective methods of participant recruitment for clinical trials. These methods are increasingly used in a wide range of targeted environments such as universities, hospitals, clinics and in the media. Patient non-compliance is another challenge for clinical trials, costing the pharmaceutical industry billions of dollars each year in lost patients. Patient compliance can be improved by implementing targeted patient recruitment and using electronic diaries as well as reminders and motivational or educational messages throughout the study, which communicate the required activity and themes of appreciation/ motivation directly to patients. Nevertheless, significant costs can be incurred by sending out reminder letters or making telephone calls to subjects to ensure compliance with the study requirements. In addition, these methods do not require interaction from the patient and there is a chance that patients may fail to respond to reminders. Providing an effective solution to the challenges of patient recruitment and non-compliance is mobile technology, which is increasingly being implemented in the pharmaceutical and

The Emergence of Mobile Phone-Based Technology The success of any clinical trial is directly related to the recruitment of good quality volunteers and patients, which in itself can be an extremely challenging task. Historically, clinical trial participant recruitment was undertaken through physician referral or by the use of paper-based mass mailing. However, these methods were time-consuming and had a very low success rate as they required the subject to make the first step. 42 Journal For Patient Compliance Strategies to enhance Health Outcomes

Volume 1 - Issue 1


Clinical Trials healthcare industries. Within clinical trials, mobile technology provides a platform for direct communication with trial subjects. With many countries enjoying 100% adoption rates for cell phones, and the cell phone being the major means of communication in others, the majority of people now consider their cell phone to be as indispensable as their wallet and keys. The majority of people carry their personal mobile phone at all times, thereby ensuring that responses are extremely fast when using text message communication for recruitment. In addition, participants are more likely to read and respond to a text message, but are less likely to respond or follow-up a phone call from an unknown number. The Benefits Mobile technology offers a number of unique benefits to clinical trial organisers, enabling them to interact directly with potential participants in a personalised and cost-effective manner. Patient recruitment and retention are considerably improved, with success rates of more than 30% compared with traditional methods that resulted in recruiting only 10% of the targeted subjects. In addition, recruitment results are delivered instantaneously compared with traditional methods where results might not be seen for weeks or months. Mobile technology can also be used to distribute automatic reminders directly and discreetly to subjects, thereby improving patient compliance. Messages can be tailored to the needs of each participant to include information such as dosage, frequency and how to take the medication safely. Delivery reports or interactive messages can also be employed to ensure that messages are received. Additionally, mobile phone-based technology enables ongoing support and motivation for a participant throughout a clinical trial, with short messages being sent in order to ensure that subjects are well-informed of the aims and benefits of the trial. Mobile phone technology can also be leveraged to facilitate electronic patient reported outcomes (ePRO) solutions. With the use of a mobile phone, sponsors are able to collect accurate data which is essential in determining the efficacy of new medication. Sponsors now have access to ePRO mobile phone technology solutions such as eDiaries to retrieve information directly from subjects. Using secure mobile online access, ePRO mobile phone technology allows patients to complete diary questionnaires via a series of text messages. Secure text messages with unique PIN codes enable patients to easily record and transmit data using their own mobile phone, facilitating data collection which is then relayed back to the clinical trial organiser. Studies have shown that eDiaries can increase patient compliance rates, reduce overall clinical development costs, improve the quality of patient reported data and minimise the time and effort required for study set-up. Real-Life Application – MDS Pharma Services MDS Pharma services, a world premier provider of innovative drug discovery and development solutions, was suffering from poor patient recruitment and patient compliance and, as a result, inaccurate data. The company urgently required a solution to rectify this challenge and ensure successful patient recruitment and compliance in the future. Traditionally, the company used a proprietary database to find potentially appropriate participants and then sent letters to each one www.JforPC.com

and awaited a response. However, the company’s target population is largely composed of university students and other young people, whose postal addresses often change, making successful contact by post difficult. Additionally, awaiting a response from a potential participant can be a lengthy process. To resolve these issues, MDS Pharma Services implemented Exco InTouch mobile phone-based communication technology for Phase I studies. MDS Pharma Services uses the technology to manage recruitment campaigns, which involve sending simple text messages to the company’s database of potential participants. The initial outreach includes up to 400 potential participants at one time. A two-way recruitment strategy has been also developed to allow participants to demonstrate interest via text messages rather than telephoning the call centre. This enables MDS Pharma Services to analyse the profiles of interested participants and easily measure response rates against study targets and deadlines. Since implementation of the mobile phone-based technology, the company has seen typical response rates of 50-60%. In addition to the patient recruitment strategies, MDS Pharma Services is also using the technology to send timed medication and visit reminders, thus reducing lost-to-follow-up early withdrawal from the studies by over 20%. Participants who wish to withdraw from the study can easily text ‘NO’ when receiving communication from MDS Pharma Services, reducing the time that the company spends on soliciting responses and ultimately improving the quality of trial results. Using the technology, the company can also overcome any potential issues that arise during the trial, being able to quickly find new suitable participants in order to meet the study deadline. Conclusion With heightened legislation and the increasing trial complexity and duration of studies, patient withdrawal and non-compliance are growing issues that require tailored, cost-effective solutions. To address these challenges, it is essential to proactively employ strategies that ensure patient retention and compliance in order to avoid compromised data, complete trial failure and heavy financial losses through replacement patients and lost revenue days. Successful retention and subject compliance are essential to the completion of a successful trial. By using mobile phone-based technology to interact directly with trial subjects, pharmaceutical sponsors can increase recruitment, retention and compliance rates in a cost-effective way that is also personal and confidential to the patient. Additionally, new ePRO technologies are also emerging, which enable clinical trials patients to complete diary questionnaires using their own mobile phones, significantly improving data capture. Tim Davis co-founded Exco InTouch in 2004. Exco InTouch is the premier provider of global, secure and regulatory compliant short messaging service (SMS) solutions to the biopharmaceutical and healthcare industries. Prior to this Tim worked in the pharmaceutical industry for over 11 years. This has included positions at Parexel and Procter & Gamble where he was responsible for the implementation and scale up of e-clinical technologies globally. Email: tim.davis@excointouch.com Journal For Patient Compliance Strategies to enhance Health Outcomes 43


Drug Delivery, Drug Packaging, Labelling & Dispensing

Creating a Value-added Packaging Design Using Web-enabled Smart Technology In 2002 the film Minority Report was released. Based on a book by Philip K Dick, it painted a picture of life in 2054, where computers are operated by voice and gestures, newspapers interact with their readers, animated billboards interact in a personalised manner with consumers as they walk by using iris-recognition technology, and cornflakes packets bearing irritating sounds and pictures keep the kids amused. This may sound improbable, but is actually not as far-fetched as you might at first think. But let’s take a step back for a minute and think about consumer needs. Any design, whether packaging or product, should start with a market need and consumer insight. People’s needs and wants can vary by age, sex, gender and demographics. Their health issues can range from a simple runny nose to life-threatening and sometimes terminal cancer. Markets themselves have their differing cultural, climatic, geographic and legislative needs. Channels to those markets are constantly evolving with product de-classification and changes such as POM-to-P (Prescription Only Medicine to Over The Counter status) switches increasing. Couple this with the rising power of supermarkets and their own-label products as brands in their own right, and it is clear that the consumer needs in each of these areas require careful thought and different approaches. For maximum consumer satisfaction and corporate profit, each ‘niche’ will benefit from suitably designed packaging solutions. However, in undertaking any research, it should be understood that people don’t always overtly explain what they want or need, and often don’t know themselves. So their unarticulated needs and compensating behaviours should be teased out as early on as possible in the design process. In parallel, packaging technology and the web are evolving, providing all sorts of intriguing opportunities for packaging design and ways of working. In addition, as these technologies converge they are providing opportunities for some great customer and patient personalisation and interaction. In 2009 two Americans, O’Reilly and Battelle, postulated that the evolving of the internet could be segmented into three distinct stages: • Firstly, 1990-2004: simple static websites that were merely brochures online, which O’Reilly likened to a ‘match being struck’. • Secondly, 2005–2009: Web 2.0, where websites became interactive and provided opportunities for uploading, downloading and sharing information, which O’Reilly likened to a ‘fuse being lit’. • Thirdly, 2010: ‘Web Squared’ was the ‘explosion’, describing the imminent exponential growth of web usage and interaction as smartphones, off the back of the iPhone, gained traction. To a great extent their prediction has been borne out, but maybe more like a ‘raging house fire’ rather than an explosion. 44 Journal For Patient Compliance Strategies to enhance Health Outcomes

So let’s look at these last two in more depth, and what their impact has been and could be on packaging and patient compliance. Web 2.0 is all about social networking, blogs, online video, wikis, Software as a Service (SaaS) and other web services, much of it residing in a ‘cloud computing’ environment. This has led to richer connections between people, organisations and individuals; richer content as people create, manipulate and store data; and more personal computing as people engage through association e.g. Facebook, Twitter and LinkedIn; augmentation e.g. Wikipedia; addition e.g. YouTube, and through collaboration, both socially and also through business with online ‘workgroups’ and ‘crowdsourcing’. A good example of how social network crowdsourcing has aided packaging design is the Connect brand developed by Vitamin Water, which through a Facebook group of over 11,000 used the power of the free peer resources in the group to build its brand and the flavour in an interactive way on the web. Web Squared takes this to the next level as more and more objects and devices go online directly and indirectly, via, for example, vision-recognition and ‘tagging’. This will enable the web to start learning by itself and will provide further opportunities for even richer interaction and crowdsourcing. So what’s the reality now? Much of this technology is already here. New York University’s Courant Institute has developed a computing interface that responds to touch, gestures and varied degrees of pressure. It will enable flipping photos across the screen, zooming, throwing them away and calling up new ones. Microsoft Research has over 10,000 staff working on similar leading-edge and exciting technology. Interactive newspapers are not quite here yet, but Sony has already developed a flat screen OLED (Organic Light Emitting Display) TV as a flexible and rollable substrate that will wrap around a pencil. This could quite easily be mounted onto a self adhesive backing to form a label. Web Squared is really being ‘technology-led’ by the everincreasing range of smartphones and ‘readers’ coming onto the market. With their sensor-based applications, microphones, cameras, motion-sensors, proximity-sensors and locationsensors (such as GPS cell-tower triangulation) and compasses, there is very little that they cannot accomplish – except maybe make a cup of tea (yet). On the Android phone platform, Google Goggles is a great example of an application that uses this technology to its full potential. It enables recognition of things via photographs taken on the phone’s camera, such as landmarks and famous paintings, but also barcodes, products and brand logos. So if you take: •G  oogle Goggles and automatic tagging (where computers and phones recognise people are things) •G  PS technology using Google Maps technology to pinpoint your position at anytime and Volume 1 - Issue 1


Drug Delivery, Drug Packaging, Labelling & Dispensing •C  ompass-enabled phones … So taking a step in to the future … This means that … in a pharmacy in the future soon … a mobile phone will be able to tell where you are in relation to other similar products and brands and direct you to those products as well. It will know who you are, what you bought last time in the store and what your particular medical condition is. To me, that sounds ‘not a million miles away’ from Minority Report. What do you think? So what fantastic opportunities does this present for packaging? Well, the most obvious are pack recognition in-store, additional product information available via the web through your phone, access to ‘drug facts’ (absolutely up-to-date), any product recall information, and also information on other similar products within the range or complementary products in the range. In future packaging needs to be ‘smarter’; not only using smart materials and technologies but packaging that: • Supports changing lifestyles • Communicates more effectively (on shelf and at home) • Is designed with consumer convenience in mind • Augments branding • Has lower environmental impact It’s also got to be packaging that better communicates. Packaging designers, brand owners and manufacturers are being squeezed from both directions – on the one hand by regulatory authorities, stipulating more and more information on packs, and from the opposite direction by the ‘green lobby’ pushing for smaller and smaller packs. Traditional printed packaging has found immediate remedies by using multi-page label leaflet solutions, but these have been pushed to their extreme with bulky multi-page formats (sometimes 50 pages+), and in future these will no longer cope. So the prospect of web-enabled solutions becoming available, together with low-cost printed displays and electronics tomorrow provide exciting possibilities. So how is this New Technology being used in FMCG? One of the key features of this new environment is augmented reality (AR), the ability to mix and match real and unreal information into a virtual world that can be used to explore the possibilities in a simulated environment - creating a mixed reality. This has already provided some fantastic (mostly marketingbased) opportunities for brand owners via product packaging. Take for example the food and snacks sector, where the Frito-Lay subsidiary in Mexico used a 2D barcode on its special Halloween version of Cheetos packs to engage consumers. After taking a photo of the barcode on the promotional pack, the application automatically launched a specific Cheetos mobile website in Spanish and delivered downloadable content. Another example is Lego, who enhanced their customers’ shopping experience in the US recently by using an AR-enabled pack that, via a pointof-sale TV screen, enabled the contents of its construction kit products to be viewed fully-assembled in 3D animation (moving pictures in real time) before purchase. But is all of this just a bit of an AR bandwagon? The aforementioned examples are mostly utility-focused, using AR to solve a problem for the consumer or end user, but they are www.JforPC.com

in the minority. Most current AR examples are nothing more than animated 3D demos, exploiting the novelty of the new technology, and are generally rather ‘clunky’. The result is that the AR space is quickly becoming very overcrowded. It won’t take long for the ‘AR novelty’ to wear off. Some would say that it is a passing fad and all just superficial indulgence, but I don’t believe that - and would argue that intelligent packaging can actually save lives! So Let’s Have a Look at the Medical Field. In undertaking a PEST analysis on the healthcare sector, it becomes apparent that there are a number of unique challenges facing the industry that are forcing pharmaceutical companies to rethink their position, change their approach and embrace some of this new technology to survive. The power of multinational businesses is increasing, but brand owners are getting squeezed by generic competition. Governments are trying to improve efficiency and cut their huge healthcare bills, as the Third World grows in economic importance and their populations have increasing disposable income. Socially, people are time-poor, have increasing mobility and environmental concerns, are more ‘net savvy’, and the growing Third World middle classes have aspirations to be like the West, with all of the trappings and status symbols. Technologically, computing power and memory is increasing, leading to smaller devices, mobile phones are smarter, and wifi hotspots are continuing to be more widely available. Trends for healthcare include regulatory and legal challenges, POMto-P switches, patient demographics and changes to healthcare systems. This presents a number of areas of concern, change and also opportunity for the healthcare sector, if only they will embrace it. There are a lot of related issues which are resulting in much work in a number of areas, such as: Braille, tamper evidence, child resistance, anti-counterfeiting and compliance/adherence. So, bearing in mind the context of this magazine and article, let’s take a closer look at compliance/adherence. Compliance/Adherence Many people with chronic health conditions fail to take medication as prescribed, and that non-compliance costs the health service £billions per year. Several attempts have been made over the years to use technology to aid compliance, including a variety of devices that: (1) beep or blip when it is time to take your medication. (2) track the number of times a dose has been removed from the medication pack, collecting data and forwarding for download at a doctor’s or pharmacy to check compliance statistics. (3) can remind a patient to take medications and confirm that they have taken it by pressing a button to send data. Some recent examples include the Stora Enso DDSI pack, Stora Enso Memori pack and the Protomed Biodose pack. However there are weaknesses with some of these, because one can never guarantee that patients have taken the correct medicine, or taken it at the right time, and their scalability for manufacture (most are only clinical trials packs and would be difficult and/or costly to automate for commercial manufacture). Journal For Patient Compliance Strategies to enhance Health Outcomes 45


Drug Delivery, Drug Packaging, Labelling & Dispensing A more recent intelligent packaging technology that better addresses this is a pack by DSM TCG B.V of the Netherlands called OtCM™ (Objective therapy Compliance Measurement), which potentially improves patient adherence for clinical trials and daily (real) practice via a system that consists of: smart medication blisters (with RFID chip), a reading device connected to a mobile phone (via near field communication - NFC) and a database with web portal. So this is an innovative use of leading-edge technology that enables safe and convenient data transfer, analysis of compliance data and diagnostic outcomes, feedback loops via SMS, email and internet, influencing patient behaviour, real-time compliance data measuring each unit dose and the measuring of real-time diagnostic outcomes. If this system were also connected up to a portable blood monitor on the patient’s arm (for instance), it could also actually monitor when tablets had been ingested and reached the bloodstream, proving conclusive evidence of full patient compliance. The problem with all of the previous examples is that they require significant changes to existing packaging to work - e.g.: • special wallets • plastic cradles or • blister amendments. To date, these technologies have been costly to introduce, difficult to scale up, and require a long development lead time. To overcome this, another step forward is a new smartphone app for clinical trials called Dose Recognition. It’s a noninvasive technology that can work with existing blister packs and packaging formats to provide a patient-friendly method of monitoring and improving compliance. The great thing is that (allegedly) the technology works across multiple packaging materials – blisters, wallets and bottles. A limitation of many of the aforementioned technologies is that they require an internet connection, but what about markets with limited web access? Another point worth mentioning is that there is also a challenge of human behaviour. Even in the West there are many technophobes who can’t or won’t adapt to this new technology (either through ability or choice) and their needs also have to be met. On top of this there are many cultural differences that may not be overcome, even with superior technology or results. What about Markets with Limited Internet Access? It’s all very well developing all of these leading edge technologies and trying to find a need against which to make them fit, but let’s take a step back to my original thoughts on consumer and market needs and think about some of the issues being experienced by Third World markets such as Africa, which will form the bedrock of pharmaceutical growth over the coming years. Malaria is a disease that kills over 863,000 Africans annually, many of whom are children, costing USD 12 billion in lost African GDP (Source: Novartis). Many of the population are illiterate. Last year, Novartis launched their award-winning and novel Coartem pack that included a full colour ‘dosage card’ that provides dosage information via clear drawings and pictograms. Its use has clearly saved many thousands of lives. It’s a great example of adapting to particular African market needs. 46 Journal For Patient Compliance Strategies to enhance Health Outcomes

Another example is Glucophage, produced by Merck and sold in Nigeria, which provides relief for diabetes and tackles the huge and growing problem of counterfeiting in Africa. The World Health Organization (WHO), estimate that counterfeiting kills hundreds of thousands every year and is said to be worth over $200 billion per year. The Glucophage packs use Sproxil’s Mobile Product Authentification™ (MPA) technology that enables consumers to text-message a unique item code for rapid response authentification. It works by consumers purchasing medications with a scratchcard attached to the pack. They scratch off a covering, reveal a unique number below, text that number (FOC) to a short code, then get an instant message back confirming ‘genuine’ or ‘fake’. So what can we Learn from this Anti-Counterfeiting Approach to Aid Patient Compliance and Adherence in Emerging Markets? Many emerging markets have limited internet access and the previously mentioned high-tech approaches to compliance / adherence are out of reach at the present time. Many of those markets don’t even have 3G connectivity. It will be many years before adequate infrastructure is in place to enable advanced web-browsing connectivity. So any of the web-enabled compliance solutions I have put forward above are useless to Volume 1 - Issue 1


Drug Delivery, Drug Packaging, Labelling & Dispensing Google Goggles, and these could guide customers (patients) to other similar products via GPS and information on other similar products / brands over the web. Longer term, RFID will supplement ‘hodgepodged’ communication to further enhance interactive experience on packs at POS and communication will become more packdriven (RFID), rather than requiring consumers to take photos of packs (i.e. ‘pull’ instead of ‘push’). Critical to the development of all this technology will be collaboration and integration with retailers and all supply chain partners. The Future: Packaging in the Home Web Squared has the potential to enable greater customer/ patient engagement through: instructions for use – to aid compliance, multilingual and interactive 3D product information leaflets (PILs) and other pack information, product shelf life and dosage warnings. It will enable deeper brand engagement, helping to build stronger emotional connections through ‘storytelling’, bringing the products to life and leading to greater brand loyalty The Future: Medical Packaging Intelligent packaging can save lives and many £billions per year. The cost drivers are more ‘forgiving’ in the pharmaceutical sector (compared to the consumer sector), meaning that RFID should be more affordable. As the average age of the population increases, the web will present all sorts of other opportunities. Smart packaging devices together with improved network infrastructures will enable enhanced interaction to provide a more holistic approach to healthcare and general wellbeing. Some say that all of this evolving technology will increasingly encroach on our privacy and human rights, and has a ‘dehumanising’ effect. The counter-argument is that these new avenues of communication will further bind us together, give us a shared context and ultimately shared identity. What do you think? them for the time being – but people are dying. However, as an example, seventy per cent of Nigeria’s population do have a mobile phone, although many of them are our old 2G ones. So to make the most of this, maybe a solution is to develop 2G solutions, like Merck have done with Sproxil in anti-counterfeiting, in the compliance/adherence arena that could provide a great interim solution.

A Summary of Packaging Opportunities The pharmaceutical market is evolving and is experiencing unique challenges never before seen. Pharmaceutical corporations need to adapt and act more quickly, more smartly and with an integrated approach. ‘Intelligent’ packaging provides a great tool to enable differentiation, end-user interaction, added value and patient compliance, but product offerings need to be more market- and consumer-focused (with end-user involvement) and take into account local, cultural and behavioural needs. The Future: Packaging at Point of Sale In the shorter term, there are opportunities for enhanced shopping experiences using interactive packs at POS. Brand identification can be achieved through applications such as www.JforPC.com

Chris Penfold is the CEO of Design Cognition Group Ltd, an independent healthcare packaging design consultancy, a Fellow of the Institute of Packaging, Vice Chairman of the East Midlands Packaging Society (UK) and a Chartered Environmentalist. He also holds positions with The Pharma Gateway and Healthcare Development Partnership. With over 25 year’s packaging advisory experience in the healthcare sector, Chris has a good understanding of packaging design & development (both graphic & structural, a wide experience of all types of materials and components and a special interest in new technologies. This coupled with his extensive knowledge of all packaging principles and processes means that he can explain complex packaging matters in layman’s terms and will also share his opinions on the current state of packaging design, technology and environmental packaging issues. Email: chris@designcognition.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 47


Drug Delivery, Drug Packaging, Labelling & Dispensing

A Tool for Designing and Evaluating Packaging for Healthcare Products Although significant resources are devoted to developing healthcare products that are safe and effective pharmacologically, significantly less effort is devoted to ensuring products perform as intended in the hands of providers and patients. Poor designs result in user confusion and frustration, and have the potential to lead to errors and adverse events. The interaction that occurs between people and healthcare products is an area in need of study. The human-package interaction framework introduced by this paper is an analysis tool to support decision-making while designing and evaluating healthcare products. According to this model, any healthcare product has: a set of intended users, varied contexts of use, and a series of tasks that users must accomplish (selection of the correct product, opening, administration, reclosing, disposal, etc.). The model provides designers with a structured consideration set with regard to the interactions between people and healthcare products. Considerations to the interface are critically needed in order to reduce the occurrence of medication errors and increase adherence. Two examples are described to illustrate the concepts. KEYWORDS: packaging, usability, adherence, non-compliance, medication error Introduction: The American National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) defines a medication error as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.”1 One way that medication errors manifest themselves is as an adverse drug event (ADE), defined as “injury due to medication.”2 By their nature, ADEs can be either preventable or unpreventable. Events that are attributable to product quality defects, medication errors or issues of non-compliance are examples of preventable events, while things that cannot be foreseen or avoided are unpreventable. Examples of unpreventable events include things like an unknown allergic reaction to a medication, or unavoidable side-effects, such as nausea and fatigue induced by chemotherapy. Medication errors and non-compliance events are closely interrelated. Some researchers have even argued that some non-compliance events could be considered medical errors.3 Irrespective of how they are classified, both medication errors and non-compliance issues are, many times, related to poor design. Consider, for example, the Office of Post-Marketing Drug Risk Assessment (OPDRA, a division of the US Food and Drug Administration), recommends interventions which include changes in the naming, labelling, or packaging of a drug product.4 48 Journal For Patient Compliance Strategies to enhance Health Outcomes

Regardless of whether the product is administered by a healthcare professional, or the patient, there is an important interaction which must occur between the human and the product. However, while a significant amount of time and resources are devoted to ensuring safety and efficacy pharmacologically, the degree to which design impacts the product’s performance in the hands of patients and care-givers is given considerably less attention.5 Healthcare products that are designed and evaluated such that they catalyse medication adherence and minimise errors are sorely needed. The correct and effective use of a drug does not simply depend on the written information of its labelling and the verbal information given by healthcare professionals; it is supported by a system of physical components such as packaging, measuring devices, applicators, dosing devices, closure systems, and the drug itself.6 All these different parts convey crucial information to patients, and their poor design is known to be a contributing factor to patient non-compliance6 and subsequent adverse events.7,8 In fact, according to the Medication Error Reporting Program (MERP) operated by US Pharmacopeia (USP) and the Institute for Safe Medication Practices (ISMP), labelling and packaging issues were cited as the primary cause of 33% of medication errors, and incited 30% of reported fatalities. A review of the literature suggests that patient confusion and lack of accessibility are at the core of usability problems with medications: • Confusion due to packaging similarity.6,8,9 • Confusion due to flawed dosing devices.10 •C  onfusion due to physical drug appearance (e.g.,tablet similarity).6 •C  onfusion because of labelling issues: distorted text, non-flat labels, small print, lack of contrast, etc.6,8, • Confusion due to drug naming issues.8, ,9,11-13 • Non-accessible packaging.6,14 One critical reason for these problems is that the scientists and regulators who have historically made decisions regarding the design of these systems frequently do not understand the complexities of human ability and behaviour. The approach has generally been product-centered (PCD) in nature. That is, traditional decisions have been driven by the technical needs of the product (i.e., a drug) and manufacturing. Decisions tend to be focused on the manufacturer’s ability to maintain the product’s safety and efficacy throughout the stated shelf life, as well as the need to produce, fill and distribute the drug efficiently. User considerations and abilities generally play a secondary role in terms of importance. We believe a more user-centred design (UCD) approach is needed. This shift is already beginning, and will likely grow, as the result of: • the costs associated with non-compliance, • global population aging, • changes in the social construct through which we view disability, Volume 1 - Issue 1


Drug Delivery, Drug Packaging, Labelling & Dispensing • the need for product differentiation in an increasingly competitive marketplace, and • the social dimension of the sustainability movement. A Comprehensive Interaction Framework Clearly, the interaction that occurs between people (i.e., users: patients and healthcare professionals) and healthcare products is an area in need of study. To provide a framework for creating and evaluating how products perform in the hands of patients and healthcare professionals, we have adapted and combined commonly accepted models from the fields of cognitive psychology and human factors; Human Processor Model15 and Usability Theory.16 The Human Processor Model is a simplified representation of the human mind. It postulates that, in order to process information and then act upon it, humans employ three systems: a) T  he perceptual system: which handles sensory stimulus from the outside world (i.e., the five senses). b) The motor system: which controls actions. c) T  he cognitive system: which supplies the processing to connect the perceptual system (input) and motor system (output). The interaction between an object (e.g., warning, label, package, etc.) and a person can be described as a cyclic information flow17 consisting of five stages (see Table 1): 1. E  xposure: the user is exposed to necessary information. Information may be in the form of the pack, features, labelling, or other components of interest. 2. P  erception: information is input into one or more of the five senses. 3. E  ncodation: the external information gathered through perception is transformed into an internal representation. This may be associated with perceived affordances stored in the long term memory (e.g., information from other sources, previous experiences, etc.). Perceived affordances provide cues about the operation of things. They refer to the object’s characteristics that are perceived by their users regarding their potential use.18 Form, colour, texture, material, and weight of a package incite certain user’s actions. 4. Comprehension: the user recognises and assigns meaning to the encoded information, thinks about the effects of using the package features, and compares the effect of the action with the user’s goals (intentions). Goals may condition recognition and vice versa. 5. Execution: thought is then translated into actions by activating voluntary muscles. In the case of packaging manipulations, the most important effectors are the arm-hand-finger and the head-eye systems. User’s actions, or reactions, may be instrumental or non-instrumental. Instrumental reactions include the use of a packaging feature to accomplish a goal (e.g., opening). Non-instrumental actions include things like touching a surface, etc. The user’s actions may cause a new state of things (e.g., opening accomplished, now dispensing must occur) and the cycle repeats until the user’s goals are accomplished. According to Usability Theory, there are four principal components in a “human-machine” system, namely: user, task, tool, and environment;16 in our argument the “tool” is represented by the design of the packaged product. Since human-package www.JforPC.com

Table 1: The five stages of human-package interactions Stage

User’s System Involved

Brief Description

Exposure

None

User is exposed to necessary information

Perception

Perceptual

Information is input into one or more of the five senses

Encodation

Cognitive

Perceived information is transformed into an internal representation

Comprehension

Cognitive

User recognises and assigns meaning to the encoded information

Execution

Motor

Thought is translated into actions by activating voluntary muscles.

Figure 1

interactions can be described by means of information flow, it can be inferred that success or failure at each step of the Human Processor Model (see Table 1) is dependent on the four components of Usability Theory (see Figure 1): 1. The user: the characteristics of the person, including perceptual, cognitive, and physical capabilities, beliefs, habits, previous experience, etc. 2. The task: the series of actions and goals to be accomplished, such as identifying, following instructions and directions, opening, dosing, reclosing, storing, disposing, etc. 3. The pack: the object of the interaction; the design of the package and product. 4. The context: the physical and social environment in which the interaction takes place. This includes characteristics like lighting, seating, distractions, temperature, pressures, other people, etc. The combination and adaptation of the existing models provides a framework regarding the needs, abilities, and desires of users with diverse goals in varied contexts. It can be used to inform the consideration set of variables which have the potential to influence adherence when designing for, or evaluating, package performance. Further, these interactions can be described as an iterative loop that consists of perception, mental processing, and action that occurs within a particular context when an individual needs to perform a specific task (or series of tasks) with a packaged product (see Figure 2). The interaction is a cyclic process in which user’s actions may cause effects leading to a new state of things, and perception is then re-evaluated in terms of user’s Journal For Patient Compliance Strategies to enhance Health Outcomes 49


Drug Delivery, Drug Packaging, Labelling & Dispensing goals. Application to Healthcare Products Designers that employ a user-centred design approach will identify users’ characteristics, contexts of use, and tasks associated with a healthcare product in order to optimise performance. For evaluation and testing purposes, this tool can be used to define testing conditions and compose user panels. Contextual conditions for testing include: the physical environment, lighting, temperature, noise, and distractions, for example. For design and development, the framework can support several design research activities such as user observation, ethnography, task analysis, context of use analysis, product benchmarking, and so on. During design phases like concept generation, prototyping, and testing, designers and engineers have the potential to account for a variety of factors affecting the usability of healthcare products. Furthermore, key design strategies are likely to be generated by analysing and prioritising such factors. The model can be used to guide and verify assumptions regarding the product and the target audience. Designers should observe and interview actual users carefully in order to incorporate insights about product use and verify their assumptions in an ecologically valid context. The next sections illustrate potential problems of adherence and medication errors that would benefit from a more user-centred approach to design. To accomplish this, we use two healthcare products (see Table 2): a) I nfant’s and children’s ibuprofen: a situation dealing with dosing and drug identification issues. b) Epinephrine injection: a situation of emergency use. Infant’s and Children’s Ibuprofen Ibuprofen is a non-steroidal anti-inflammatory (NSAID) analgesic antipyretic (lowers body temperature without impairing consciousness) that, at higher doses, reduces inflammation. Our example utilises two formulations, one for infants and a second for children, both with the active ingredient ibuprofen. The infant formulation consists of a concentrated liquid oral (50 mg per 1.25 mL)19 and is intended for infants aged up to 23 months. Children’s ibuprofen is also an oral suspension. Its concentration is 100 mg of active per 5 mL19 and it is intended for children between 2 and 11 years of age. Both products are supplied in bottles. Each product has a specific dosing device: a standard syringe for the infant product and a thermoformed plastic cup for the children’s version. The user of either product is not likely to be the actual patient. It may be a parent, a grandparent, a babysitter, or a healthcare professional. Designers will have to consider users with different levels of education, and a broad range of abilities (i.e., perceptual, cognitive, and physical) and experience. Varied contexts of use include different rooms of a house (e.g., bathroom, kid’s bedroom, kitchen, and so on) or even an on-the-go situation (e.g., car, other house, a public place, etc). In the worst case scenarios, light might be inadequate, for example, because it’s late at night and parents simply do not want to awaken the child. Typical tasks include storing, identifying the correct product from among many, locating and understanding correct dosage 50 Journal For Patient Compliance Strategies to enhance Health Outcomes

Table 2: Summary breakdown of users, contexts of use and tasks for two common healthcare products. Packs

Users

Contexts of use

Tasks

Infant’s and Children’s Ibuprofen

• Parents • Care-givers • Healthcare professionals

• Indoors • On-the-go

• Storing • Identifying the product among other drugs • Understanding information about dosage • Opening and closing childresistant bottles • Dispensing and measuring • Disposal

Epinephrine injection

• Children • Teenagers • Adults • Older adults • People with disabilities

• Outdoors • Indoors • On-the-go

• Carrying the device • Identifying the needle tip • Removing its safety feature • Holding it in the right position • Applying the injection • Disposal

Figure 2

information, opening child-resistant packages, dispensing and measuring by means of a dosing device, reclosing, and, eventually, disposal. The challenge is to simultaneously consider the factors presented in the model in order to optimise the likelihood of successful administration of the product. For instance, locating and comprehending the correct dose might be particularly challenging for users not familiar with metric units or not formally trained regarding medications, but may be readily understood by those who are. If the dosing device is designed in such a fashion that it is difficult to perceive (e.g. poor contrast, inadequate embossing of units or text that is too small), mistakes could be made even if the care-giver thoroughly understands the dosing instructions. These difficulties can be further exacerbated by the context undergirding the interaction, such as the lighting of the environment and the condition, location and behaviour of the child, which have the potential to add stress to the difficulty. A specific combination of events may conspire to confuse the user, inducing them to dose a child with the more concentrated infant product using the wrong dosing device, ultimately resulting in a medication error. For instance, different standard syringes might be available to the user, with no markings identifying their respective drug product. As such, a child could receive the right drug at the right dose but in the wrong concentration Volume 1 - Issue 1


Drug Delivery, Drug Packaging, Labelling & Dispensing because of an identification problem related to the packaging and dosing device. Inconsistencies in the measuring devices for children’s liquid oral dosages that are likely to lead to care-giver confusion are documented.10 In fact, largely as the result of numerous, documented, unintentional overdoses involving liquid oral formulations, both the industry20 and the US Food and Drug Administration (FDA) have released guidances regarding the inclusion, markings and abbreviations appropriate to these devices. 21

closure systems, and the drug itself.6 These components convey important information regarding the safe and effective use of the products. The human-package interaction framework (presented herein) indicates that any healthcare product has a set of intended users, a set of contexts of use, and a series of specific tasks that must be accomplished. The framework serves to support the design and evaluation of products in an attempt to reduce the occurrence of medications error and increase adherence.

Epinephrine Injection Epinephrine is generally administered parenterally; typically in the form of an injection used to treat life-threatening allergic reactions caused by insect bites, foods, medications, latex, and other causes.22 It is packaged in varied forms, which include a single-dose pre-filled automatic injection device that is applied in a “swing and stab motion” into the thigh. Patients and their care-givers are instructed to administer epinephrine at the early signs of a serious allergic reaction (as indicated by swelling redness, etc.). Users of epinephrine injections have a wide range of abilities, as they include children to older adults, and the drug may be self-administered or administered by a care-giver (e.g. healthcare professional, parent, teacher, babysitter, etc.). Care-givers, in particular, may or may not be familiar with the appropriate use of the device that delivers the drug. Given the critical context of use (time is of the essence in a potentially life-threatening situation) and the varied experience levels of those likely to administer the drug, clear and simple directions regarding this product are paramount. This product will always be used under a high level of stress and rush induced by the emergency nature of the need for it. Other characteristics of the context of use are incredibly varied and will likely include: outdoors, indoors, public places, homes, schools, vehicles, etc. A usage scenario can be conjured for literally any place. The set of tasks include carrying the device (some users may actually “holster” this drug to themselves due to the timecritical nature of its use), identifying the needle tip, removing its safety feature, holding the device in the right position, and administering the drug successfully (which in and of itself has a series of steps). These steps may look easy to replicate, but the combination of poorly designed devices, untrained users, limited time for reasoning, and a stressful context complicate the process, making clear and straightforward design requisite for success, with potential life-threatening implications resulting from poor designs.

References 1. N  ational Coordinating Council for Medication Error Reporting and Prevention. About medication errors: What is a medication error? 2007; http://www.nccmerp.org/aboutMedErrors.html. Accessed March 16, 2011. 2. B  ates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. JAMA: The Journal of the American Medical Association. 1995;274(1):29-34. 3. B  arber N. Should we consider non-compliance a medical error? Quality and Safety Health Care. 2002;11:81–84. 4. U  S FDA. FDA 101: Medication Errors. 2009; http://www.fda. gov/ForConsumers/ConsumerUpdates/ucm048644.htm. Accessed March 18, 2011. 5. DeWalt DA. Ensuring safe and effective use of medication and health care. JAMA: The Journal of the American Medical Association. 2010;304(23):Published online November 30, 2010. 6. W  ard J, Buckle P, Clarkson JP. Designing packaging to support the safe use of medicines at home. Applied Ergonomics. 2010;41(5):682-694. 7. F ood and Drug Administration. Guidance for industry. Dosage delivery devices for OTC liquid drug products. November, 2009; http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ UCM188992.pdf. Accessed December 6, 2010. 8. Berman A. Reducing medication errors through naming, labeling, and packaging. Journal of Medical Systems. 2004;28(1):9-29. 9. M  cCoy LK. Look-alike, sound-alike drugs review: include lookalike packaging as an additional safety check. Joint Commission Journal on Quality and Patient Safety. 2005;31(1):47-53. 10. Y  in HS, Wolf MS, Dreyer BP, Sanders LM, Parker RM. Evaluation of consistency in dosing directions and measuring devices for pediatric nonprescription liquid medications. JAMA: The Journal of the American Medical Association. 2010;304(23):Published online November 30, 2010. 11. K  enagy JW, Stein GC. Naming, labeling, and packaging of pharmaceuticals. American Journal of Health-System Pharmacy. 2001;58(21):2033. 12. L ambert BL, Lin SJ, Chang KY, Gandhi SK. Similarity as a risk factor in drug-name confusion errors: the look-alike (orthographic) and sound-alike (phonetic) model. Medical Care. 1999;37(12):1214-1225. 13. U  S Pharmacopeia. Look-alike/sound-alike drug products affect cognition. 2004; http://www.usp.org/pdf/EN/patientSafety/ capsLink2004-05-01.pdf. Accessed December 21, 2010. 14. d  e la Fuente J. The use of a universal design methodology for developing child resistant drug packaging. East Lansing: School of Packaging, Michigan State University; 2006.

Conclusions A majority of efforts regarding the design and evaluation and drugs is devoted to understanding the chemical aspects of the packaged product so that it is assured to be safe and efficacious throughout its stated shelf life. Yet, in virtually every instance of healthcare, there are people (be they the patient themselves or a care-giver – trained or untrained) who must interact with the packaged product such that it is administered safely and effectively. As a result, the safety of patients is partially dependent on a system of physical components such as packaging, measuring devices, applicators, dosing devices, www.JforPC.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 51


Drug Delivery, Drug Packaging, Labelling & Dispensing 15. C  ard SK, Moran TP, Newell A. The psychology of humancomputer interaction. Mahwah: Lawrence Erlbaum Associates, Inc.; 1983. 16. S hackel B. Usability - Context, framework, definition, design and evaluation. Interacting with Computers. 2009;21(56):339-346. 17. M  onk A. Cyclic interaction: a unitary approach to intention, action and the environment. Cognition. 1998;68(2):95-110. 18. N  orman DA. The psychology of everyday things. New York, NY, USA: Basic Books.; 1988. 19. A  ll about kids Pediatrics. Ibuprofen dosage. 2011; http://www. allaboutkidspediatrics.com/parents/dosage.html. Accessed March 19, 2011. 20. C  onsumer Healthcare Products Association. Guideline Volumetric Measures for Dosing of Over-the-Counter Liquid Oral Drug Products for Children ≤ 12 Years of Age. 2010; http://www.chpa-info.org/scienceregulatory/Voluntary_Codes. aspx#volumetricmeasure. Accessed March 21, 2011. 21. U  S Department of Health and Human Services US Food and Drug Administration. Guidance for Industry: Dosage Delivery Devices for OTC Liquid Drug Products. In: (CDER) CfDEaR, ed2009. 22. P  ubMed Health. Epinephrine Injection. 2008; http://www.ncbi. nlm.nih.gov/pubmedhealth/PMH0000211/. Accessed March 19, 2011.

Javier de la Fuente is co-director of Factor IDD, a design consulting company specializing in packaging and product design. He is pursuing a doctorate at the Michigan State University School of Packaging. His current research focuses on usability issues of flexible packaging. He earned his Master of Science degree from the same school and holds a fiveyear degree in Industrial Design from the University of Buenos Aires, Argentina. Email: cjd@msu.edu Laura Bix, Ph.D Dr. Bix is an Associate Professor at the School of Packaging at Michigan State University. She was appointed, and currently serves as the US delegate to ISO TC122 WG 9, a group which is developing a standard for measuring the accessibility of packages. Bix served as the Vice-Chair of Committee D10.32, the Committee on Consumer, Pharmaceutical and Medical Packaging, from 20042007, and as a member of Committee F-02, the flexible barrier material committee, from 2002-2008. In 2008 she was named one of the 100 most notable people in the medical device industry by Medical Devices and Diagnostics Industry. Email: bixlaura@anr.msu.edu


Drug Delivery, Drug Packaging, Labelling & Dispensing

The Role of Qualitative Research in Patient Comprehension Testing for Product Labels and Medication Guides The US Food and Drug Administration (FDA) deems that for a drug or medical device to be considered safe, its labelling needs to provide “adequate directions for use” (Food Drug and Cosmetic Act, 2011). As communications are often directed to patients who use these health products, “adequate directions for use” means directions under which the layman can use a medicine or device safely and for the purposes intended. To fulfill the obligation to provide patients with adequate usage directions, companies often test their product label to ensure that the information provided can be understood by the average patient or consumer. There are several types of testing that can be undertaken to determine if patient information is sufficient. For example, companies can perform readability tests to determine reading ease, paper and pencil tests to measure knowledge of and memory for provided information, or usability tests to measure ability to follow directions. Each of these types of studies, however, measures a different aspect of the communication. McGuire (1980) suggests that communications require the successful completion of a series of steps to ensure that people are exposed to the message, pay attention, comprehend, accept, remember and use the information in decisions and to guide behaviours. The type of testing applied varies with the goal of the research (at which steps the research is directed). In theory, a company could engage in many different types of patient or consumer research needed to test for successful completion of each of the steps of communication. However, such exhaustive testing is likely to be costly in terms of money and time. Furthermore, an improvement at one step (e.g., putting certain information in bold typeface) may improve attention to that information but be counterproductive at another stage (e.g., decreasing attention to other supporting information and thereby decreasing understanding of the concepts being tested). Given the need to provide “adequate” directions for use, much of the focus of health information testing has centred on the comprehension of information. This step encompasses previous steps (attention) but does not seek to measure if the information affects decisions to use the product. Comprehension testing is often accomplished through the use of structured interviews based on a devised questionnaire (Morris et al, 1998). Recruited patients or consumers representative of the user population are provided the label information and asked a series of questions to measure their understanding. Sometimes reading the information and testing occurs immediately (as in over-the-counter [OTC] drug comprehension tests) and sometimes it occurs after a considerable delay (as much as several months as in Medication Guide evaluations). The questionnaire seeks to measure the important messages in the document. The questions are usually based on specific “communication objectives” of the document (most important messages for safe and effective use). www.JforPC.com

Limiting the questioning to a few specific aspects of the presented information often results in a limited number of questions that merely measure recall of presented information. Even asking brief questions that require people to integrate information from various aspects of the communication may simply test their memory for facts, with little effort given to test how the information relates to their own use of the medicine. While such memory is important, it is not a true test of patient understanding or a measure of whether the “directions for use” are “adequate.” Components of Comprehension In order to determine whether we can successfully measure comprehension of patient information, we must consider what is involved with the process. As suggested previously, the goal of providing information to patients is to maximise the ability of individuals to use the product safely and effectively. To provide such knowledge requires people to “fully process” a document, which involves several “processes” that underlie comprehension. Figure 1 describes these processes. First, people must be able to “encode” the information; that is, they must be able to translate the information presented on the page to some concept that they can store in their memory Figure 1: Processes underlying comprehension and ability of patients to use medicines safely and effectively

(Rypma & D’Esposito, 1996). If the information presented to patients uses unfamiliar or difficult to understand terms, the consumer may not be able to “transfer” the information into memory or further process the information unless they take the time to search for the definition and meaning of the presented terms. Even if the terms can be adequately defined by the patient, the concepts involved may be poorly “interpreted” if the explanations are vague or inadequately presented. If there is a great deal of information presented to the individual in a patient information sheet (high cognitive load), the reader may need to select out (or “parse”) the critical information from the presented details. If the essential information is difficult to discern (information overload) the key details may be lost (not encoded) (Bruce, Edwards & Lupton, 2006). The transfer of information into memory structures is usually viewed as the process by which new information is “integrated” Journal For Patient Compliance Strategies to enhance Health Outcomes 53


Drug Delivery, Drug Packaging, Labelling & Dispensing with existing concepts stored in memory, or new concepts are created in patient memory (Prabhakaran, Narayanan, Zhao & Gabreili, 2000). Van den Broek (2010) proposes the “landscape model” of text processing, where key concepts, and the details relating to those concepts, are explored to determine the basis of information underlying what is known about an issue (such as proper use of a medicine). This provides a measure of “understanding” that can be assessed to determine whether comprehension is sufficient or insufficient (i.e., if people do not understand the key concepts sufficiently to use a product correctly then comprehension is incomplete). This integration is a sustained process by which information is temporarily stored in “working memory” and later transferred and applied to other existing memory concepts (consolidation and reconsolidation) (Lee, Everitt & Thomas, 2004). The important aspect of determining whether the integration of information into memory is sufficient is to consider how the information is to be used. If consumers need to understand that they should not eat citrus fruit when taking the medicine, they must be able to relate this information to key concepts. They need to understand what is meant by “citrus fruit” and they also need to understand what is meant by “taking the medicine.” Citrus fruit represents a “context-independent” concept, meaning that regardless of the context provided, people may be able to discern which products are citrus fruit and which are not. Taking the medicine is a context-dependent concept, meaning that this is an abstract concept whose meaning can vary depending on the broader messages provided by the communication. The timeframe between eating citrus fruit and ingesting a capsule of a medicine can vary considerably; from never eating the fruit during the entire time a medication is used (e.g., a lifetime for chronic medicine) or during a short timeframe (e.g., 10 minutes) after a medicine tablet is ingested. Successful integration means that the information retained in memory about key concepts is sufficient for patients to use the product as intended (Alba & Alexander, 1981). Whether the medication information is sufficient can only be assessed by determining how the information is applied to potential usage situations. Thus, the “application” of information to potential usage situations must be assessed to measure if comprehension is sufficient to promote correct usage decisions. People must be able to extract the essence of the message, correctly inferring what is meant by the message as it applies to their own situation (Mason & Just, 2004). Need for Qualitative Research The major advantage of quantitative research is that the data generated by such research is definitive (can be scored as correct or incorrect) and analysable in terms of relative degrees of success (e.g., 85 per cent of the tested sample correctly answered a question). The major disadvantage of quantitative research is that there are a limited number of questions posed in any study, and it is not clear whether the presented questions measure all of the concepts needed to ensure that the drug is used properly or that the concepts are explained sufficiently. Qualitative research is not definitive (usually small sample sizes, overly broad responses that may be difficult to analyse). However, the major advantage of qualitative research is that it can provide a knowledge base for patient information designers to analyse what patients need to know about the 54 Journal For Patient Compliance Strategies to enhance Health Outcomes

concepts presented so that the drug can be used in the manner intended. Decisions about what information to include, how much information to provide and what types of explanation are needed to fully describe a concept can be based on feedback from prototypical patients. Extraneous details (information not necessary for comprehension of important directions) can be identified. These “seductive” but irrelevant details could detract from comprehension of more important information and their deletion could improve comprehension (i.e., reduce information overload) (Harp & Meyer, 1998). Qualitative Research Procedures To conduct qualitative research, we suggest the following procedure. Overall Approach: to perform qualitative research, we suggest using focus groups of 8-12 individuals who are patients or consumers prototypical of patients who use the product. Respondents are recruited using a screening questionnaire that eliminates people who are not prototypical (e.g., health professionals, people who work in the pharmaceutical industry). Quotas for age, gender or education can be established to recruit a mix of patients. A single group of participants who speak English as a second language may provide a unique perspective. Two to four focus groups are recommended for each product tested. The group discussion can be conducted at a facility with a one-way mirror and viewing room for observers. Recruited respondents can be sent the material prior to attending the Volume 1 - Issue 1


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group if the material is long and reading would take significant time away from group discussion. Group Agenda: the group discussion is based on a detailed interviewer guide. Developing this guide is the basis of the qualitative data to be derived. It contains a detailed listing of topics to be probed along with timeframes to guide the discussion. The discussion usually starts with introductory remarks explaining the topic to be covered and eliciting the help of the participants in aiding to understand how well the document communicates important information and what can be done to improve the document. Respondents are treated as experts who understand what information is helpful, what they do or do not fully understand, and what does or does not make sense to them. First, general impressions and beliefs are solicited about how well the document communicates important information, willingness to read the document and barriers to understanding the concepts (e.g., physical appearance of the information (legibility, graphic emphasis on certain phrases), use of unfamiliar words, overall length and burden to read). Information is solicited about specific parts of the document (words, phrases, sections) that are difficult to understand (or had to be read more carefully than other parts). This section may provide important details that an overly broad review by technical experts can miss. For example, a technical expert may find a document to be long and burdensome to read. However, a group may state that although the overall length of the document is considerable, it www.JforPC.com

may not be viewed as a sizeable barrier because the information is important and they were are willing to invest the time and effort to read information they believe is relevant and necessary for safe use of the product. Next, each section of the document is reviewed by the group. Understanding of the individual topics within the section is solicited; asking for any parts (words or phrases) that present a problem with understanding. After impressions are solicited, specific probes are provided and group reaction is elicited. Here, interviewers rely on their own analysis of the document. Key concepts can be identified and respondents are asked to explain what is meant by that concept. For example; if taking too much of a drug may result in an “overdose” the participants can be asked to explain what is meant by that term. More specific probes can be added to probe understanding (e.g., what type of dosing behaviour (frequency, amount) may cause an overdose)? Any inferences needed to understand how to use the product correctly can be solicited and probed. For example, if patients are informed to avoid excessive sunlight because of photosensitivity, we can probe what is meant by “excessive sunlight”. Next, examples of what would or would not be acceptable can be probed (can a person go to a tanning parlour? what about working outside in the summertime?). By soliciting how respondents interpret and apply the information, the depth of their understanding can be probed. Further, circumstances where they have questions can be raised (e.g., can I go outside at all if I do not use a hat?). Inconsistencies within the document can be probed. There may be multiple types of inconsistencies. For example, information placed in a section may not be consistent with the topic headings (information about when not to use the medicine (that more logically should be placed in the contraindications section) may be placed in a precautions section. Having an inconsistent message may also occur when there were differences between the summary section of the leaflet listing contraindicated behaviour and a later section that went into more detail. While summarisation may be viewed as helpful, differences in specific listed behaviours that are acceptable or illadvised can be confusing. A third type of inconsistency may be in the way in which graphic emphasis is applied. The document may use bold typeface to emphasise certain messages. However, in some places single words can be bold, in other places longer phrases can be bold and in some places whole sentences or paragraphs can be set off in bold typeface. Making the look of the document consistent, as well as the messages provided, is an important method of providing helpful information. Ways to reduce the cognitive load can be solicited in the group discussion. Sometimes, “educational” information that is provided to improve general information may be confusing or detract from overall understanding of the key concepts necessary to use the product safely. For example, for a weightloss medicine a leaflet had an explanation of the term “BMI” (body mass index). The discussion was “interesting” and provided “educational” material but was not necessary to explain what the drug did or how it was to be used. While such information might serve an intellectual goal, it would not change how people use the medicine. Thus, discussion of these “seductive details” could be omitted. Another way to reduce cognitive load was to reduce repetition from section to section. Although “repetition” Journal For Patient Compliance Strategies to enhance Health Outcomes 55


Drug Delivery, Drug Packaging, Labelling & Dispensing is often viewed as improving memory for information, it can also be detracting from a patient’s willingness to pay attention (assuming that the person already knows the information). Stating the message in a context that expands its application to additional situations may help to reinforce the message while avoiding the notion that the information has already been read. Simply “pruning” the individual sentences and paragraphs to make them shorter and more informative (reducing information overload) can also be helpful. Some confusing and burdensome information can be clarified by reorganising the information into more coherent sections. Simply moving information so that it flowed more logically in the respondents’ mindset can be helpful with improving respondents’ ability to integrate the information into memory. Reorganising longer lists into a series of shorter lists (with headers that inform the reader what was covered in the list) (chunking) may be a helpful way to reduce cognitive burden and improve understanding and memory for the information. In general, feedback from the qualitative test provides several ways to improve the document. It can add details to make the information clearer and more usable. It can identify areas where one can omit information, making the document less burdensome to read. It can target areas where to reword sentences and paragraphs, remove redundancy, and improve consistency to improve understandability and reduce the potential for information overload. By simply moving information into more meaningful, coherent and briefer sections one may be able to make the document more digestible from an information-processing standpoint. In theory, a company could attempt to rework a document using a communications expert. The same cognitive principles discussed by the groups could be applied by such an expert. However, the expert would not have the same perspective as potential users of the medicine. We submit that users of a medicine are experts on how the information relates to them and their own background knowledge and beliefs. Cognitive experts can help apply communication principles; however, without insights into the knowledge base or expectations of potential users, cognitive experts are at a distinct disadvantage. Qualitative feedback from potential users supplies valuable insights into how patient communications can be structured and phrased to make them truly comprehensible. References Alba, J. and Alexander, S. The role of context in the encoding of information. J. Experimental Psychology, 1981, 7(4), 283-292. Bruce, C., Edwards, S. and Lupton, M. Six Frames for Information literacy Education: a conceptual framework for interpreting the relationships between theory and practice. January 2006. 5(1): Available at: http://www.ics.heacademy.ac.uk/italics/vol5-1/pdf/ sixframes_final%20_1_.pdf, Accessed March 3, 2011. Federal Food, Drug and Cosmetic Act (FD&C Act): Available a t / w w w . fd a . g o v / r e g u l a t o r y i n fo r m a t i o n / l e g i s l a t i o n / federalfooddrugandcosmeticactfdcact/default.htm, Accessed March 3, 2011. Harp, S and Mayer, R. How Seductive Details Do Their Damage: A Theory of Cognitive Interest in Science Learning. Journal of 56 Journal For Patient Compliance Strategies to enhance Health Outcomes

Educational Psychology, 1998, 90, 3, 414-434. Lee, J., Everitt, B. and Thomas, K. Independent Cellular Processes for Hippocampal Memory Consolidation and Reconsolidation. Science, 2004, 304, 839-843. Mason, R. and Just, M. How the brain processes causal inferences in text. Psychological Science, 2004, 15(1), 1-7. McGuire, W. The communication-persuasion model and health-risk labeling. In L. Morris, M. Mazis and I. Barofsky, Product Labeling and Health Risks, New York: Cold Spring Harbor Laboratories, 1980. Morris, L.A., Lechter, K., Weintraub, M. and Bowen, D. Comprehension testing for OTC drug labels: Goals, methods, target population, and testing environment, Journal of Public Policy and Marketing, 1998, 17(1), 86-96. Prabhakaran, V., Narayanan, K., Zhao, Z. and Gabrieli, J. Integration of diverse information in working memory within the frontal lobe. Nature Neuroscience, 2000, 3(1), 85-90. Rypma, B. and D”Esposito, M. The roles of prefrontal brain regions in components of working memory: Effects of memory load and individual differences. Proc. Natl. Acad. Sci, 1999, 96, 6558–6563. Van den Broek, P. Using Texts in Science Education: Cognitive Processes and Knowledge Representation. Science, 2010, 328, April 23, 453-456. Louis A. Morris, Ph.D., is President of Louis A. Morris and Associates, Inc which provides research and consulting services. Dr. Morris worked for the US FDA for 23 years and held faculty appointments at several universities. He has authored over 100 journal articles and book chapters on the topics of health and risk communications. Email: lmorris@optonline.net Lauren E. Sandstrom, BSN, RN, MBA, is Assistant Director, Pre-marketing Safety Assessment in Risk Management and Epidemiology at Purdue Pharma L.P. Her experience includes 20 years in the pharmaceutical industry with a focus on clinical and drug safety, and a diverse clinical nursing background. Email: lauren.sandstrom@pharma.com Paul Coplan is Executive Director and head of Risk Management and Epidemiology at Purdue Pharma and Adjunct Assistant Professor at the University of Pennsylvania School of Medicine. He has a Doctorate in Epidemiology from Harvard University and an MBA from Wharton Business School. He conducted studies in 15 countries and published 45 journal articles. Email: Paul.Coplan@pharma.com Volume 1 - Issue 1


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Are all MDS created equal? The common myths of compliance laid bare Recent articles in industry ‘bibles’ The Pharmaceutical Journal1 and British Medical Journal2, have highlighted that common misconceptions about MDS3 endure, even among the country’s senior pharmacy and medical professionals. The myths around MDS are so deeply ingrained, even GANFYD, the GP’s answer to Wikipedia, has got it wrong4. As technology continues to progress apace, the creator of the first British-designed monitored dosage system, Protomed’s Norman Niven, brings us up to speed on the truths and myths of MDS. Dementia, complex drug regimens and forgetfulness all contribute to drug error with self-medicating patients. In a hospital, care home or in domiciliary care, limited time and resources, plus a lack of training, vastly increase the risk of drug error and jeopardise patient welfare. Even in this, the information age, an outdated understanding of MDS technology is standing in the way of vast savings and improvements in patient outcomes. With the cost of drug error estimated at between £2.7 billion and £4 billion5, an understanding of countermeasures to the compliance problem is no longer an ‘optional extra’ for residential homes and soonto-be GP consortia. Life Before MDS Since they were introduced into the UK in 1989, monitored dosage systems have become a crucial tool in combating the numerous obstacles to compliance. Before MDS came onto the market in the late eighties, the way medication was administered in care homes (especially in the local authority care homes of the day) was archaic, dangerous and wholly inadequate. The introduction of MDS solved the problem and in the process, totally transformed the relationship between community pharmacies and care homes, giving pharmacies an important new USP and revenue stream. Some 20 years later, thanks to MDS, medication management is safer, more efficient and better organised than ever. The level of drug errors has fallen and the audit processes in place mean error is more easily detected.

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Growing Pains The introduction of MDS was not without its difficulties; and even two decades on, these ‘teething troubles’ continue to haunt MDS. Initially, some care professionals suggested that MDS was the beginning of the ‘deskilling’ of nursing, as medication management systems were safe and easy to use by non-skilled staff. But the fundamental problem with MDS was the question of how it would be paid for. When early monitored dosage systems first appeared in 1989, Boots – the first movers in the market – offered to provide MDS systems free of charge. This set a precedent which later became the norm. Many pharmacies resented this situation back in 1989, and specifically, the expectation that this valuable yet resource-intensive service should come for free. A difficult route to market and its associated costs have weighed heavily on MDS over the years and have deflected attention away from the remarkable progress this innovation has brought about in standards of healthcare. Clearly, MDS carries with it a lot of baggage and it is this baggage rather than actual issues that, even 20 years later, still has a significant impact on the market and distracts us from the reason why MDS was created in the first place. So let’s dispel some of the outdated but lingering assumptions about MDS. Myth One: MDSs Don’t Accommodate Liquids The British Medical Journal recently made the following announcements: a) that prescribers are four times more likely to give the wrong dose of medicine with liquid prescriptions compared with tablets and b) monitored dosage systems don’t accommodate liquid medicines6. Spot the incorrect statement. The latter is the most outdated (yet still extremely common) assumption in the world of MDS; that systems are only suited to solid dosage forms. This myth dates back 20 years to a time when MDS was in its infancy. Quite simply, the technology to pack liquid medicines into a monitored dosage format was not available. Even now, Biodose is the only MDS to accommodate liquids and tablets. Such is the cutting-edge nature of the technology needed to

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Drug Delivery, Drug Packaging, Labelling & Dispensing make this possible, that the liquid-friendly system is protected by no less than five patents. To date, the vast majority of MDSs on the market have tried to get around the obstacle of accommodating liquids by including reminder cards that direct carers doing the drug rounds to any medications not packed within the MDS (ie liquid oral medication and topical medicines such as gels and creams). This extra step in the process opens up yet another opportunity for human error to set in, and defeats the object of centralising all of a patient’s medications in one system. Biodose was developed to overcome this issue. Given that to date, it is the only system to accommodate liquid and solid medication side by side, it’s understandable that this particular myth is still doing the rounds. However, the availability of a single anti-error solution that accommodates all dosage formats makes MDS technology accessible to a vast new audience that may have previously written it off. In truth, the problem of noncompliance is more prevalent in the elderly, and the elderly are more likely to suffer from swallowing difficulties and require their medicines in a liquid format. Therefore dispelling the untruths around liquids and MDS is vital to improving quality of care for older patients. Myth Two: MDSs can Store a Maximum of Four Doses per Day This common misconception portrays MDS as an inflexible system that is appropriate for a limited number of patients. With the average number of prescriptions dispensed annually to people over 60 having doubled in a decade7, and elderly patients in care homes taking an average of eight prescribed medicines per day8, a four-a-day system would be useful for only the minority of older patients. True, the majority of MDSs are limited to accommodating doses at mealtimes and before bed, which makes compliance almost impossible. However, a minority of systems allow virtually unlimited doses during the day, to take account of the importance of accurate timing and the complexity of many drug regimes, particularly for the elderly. Containing sufficient doses for the patient is crucial to the efficacy of an MDS, and all systems are certainly not created equal in this respect. The most sophisticated systems incorporate software that can adapt to up to 11 dosage intervals throughout the day, which don’t have to be limited to breakfast, lunch and dinner. This means each individual dose is labelled with the specific time the medicine should be administered, leaving the minimum room for error to creep in, whether the patient is selfmedicating or in a care home environment.

Myth Four: MDS Only Applies to Oral Medicines US studies show that non-compliance is as great a barrier to recovery in the context of topical medication as it is in oral medication. In the field of dermatology, it is observed that “poor compliance with treatment advice in chronic conditions represents a major challenge”, and that the rate of noncompliance may be as high as 40 per cent9. Despite the fact that the immediate physiological consequences of not applying creams and lotions as prescribed is perceived as less threatening, it clearly contributes to the estimated £150m of avoidable medicine waste in the UK10. In the past, MDSs have focused on oral medications, and only now are more advanced tools coming onto the market to help counteract topical drug error and provide a more comprehensive approach to the compliance conundrum. As well as accommodating larger quantities of liquids, such as creams, gels and ointments, in separate, safely sealed containers, the more sophisticated systems such as Medigram have proprietary software that creates an MAR sheet specific to topical drugs, in the form of a body map. This literally maps out the areas where medication is to be applied to the patient, aiming to make the process as foolproof as it can be. So while the topical MDS is a new development, expect to see it used more and more in future as budget-holders in healthcare look to plug the leaks in their steadily shrinking drug budgets. Myth Five: One Size Must Fit All The options available to help manage medicines have multiplied beyond belief in the last 20 years. The days of housing tablets in egg cups are long gone, and in their place is a variety of

Myth Three: Medication in MDSs has a Short Shelf Life A recent pharmaceutical journal article stated that temperature-, light- and moisture-sensitive drugs would perish in an MDS, but there is no clinical evidence for this. Indeed, there are no scientific studies to suggest medication deteriorates when housed in an MDS, just a mountain of supposition, conjecture and disinformation. The alternative to MDS – the cold seal blister packs (that are often poorly sealed) – have been used for years. Were there a problem with tablets deteriorating, it would certainly have come to the fore by now. So given MDS’s 20-year pedigree, and the absence of any evidence to the contrary, this particular MDS myth is entirely unfounded. For the normal life span of medication in care homes, MDS raises no deterioration issues at all. 58 Journal For Patient Compliance Strategies to enhance Health Outcomes

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Drug Delivery, Drug Packaging, Labelling & Dispensing intelligent systems designed to take the thought and the risk out of the drug-administering process. Despite the speed of innovation in MDS, the diverse spectrum of options on the market ranges from the very simplistic (Dosette boxes and blister packs) to the sophisticated. With so many preconceived (and often inaccurate) ideas about what MDS can (and can’t) do, many end users are still in the dark as to the features and benefits they can expect from a system. As more and more copycat products enter the market, to differentiate one from another, carers, pharmacists, doctors and individuals will be asking the following questions: • Can it contain liquid and solid oral medication? • Can it accommodate creams and ointments? • Does it accommodate all the doses needed throughout the day? • Is it easy for the patient or carer to use? • Are the dosage instructions, time and patient details clearly visible? • Are the medicines clearly identified on the tray? • Is the system tamper-evident? • Can individual doses be removed to take on days out? If so, are their instructions / patient details on each individual dose to maintain continuity of compliance? • Does it have any features to combat MRSA, such as antimicrobial packaging? • Does it incorporate away-day packs for patients or residents who need to take medication out for the day? • Does it remove the need for pouring liquids at the bedside? • Does it allow the accommodation of all tablets and capsules, including hygroscopic and soluble medication? What’s Next for MDS? At the more advanced end of the innovation scale, telehealth is on the horizon; an area where Protomed is investing heavily to help develop the next generation of MDS technology. Soon, MDS will be compatible with SMS and e-mail technologies to improve the flow of information about patients’ compliance (or otherwise) between relatives, carers, medical professionals, pharmacists and nurses. But what will the fusion of MDS and telehealth look and feel like? Picture this. 85-year-old Frank, who lives alone, pops open his MDS pod for the day. Through a microchip embedded in the seal, this automatically sends an e-mail alert to his GP and logs the time in a database to be reviewed at his next MUR with Frank’s local pharmacist. Over the next few days, Frank starts missing doses, which triggers a rule pre-programmed into the system, and sets off another chain of events. A warning text is sent to Frank’s relative (much in the way of a personal alarm) and GP to prompt them to check on him and find out why he isn’t taking his medication as prescribed. The move to telehealth will see pharmaceutical companies working alongside community pharmacies to manage patient compliance by individual drug type and therapeutic area. Pharmacies will be paid on a fee-forservice basis, improving their revenue-raising potential in the face of inevitable reductions in the NHS drugs budget. For the pharma industry, the benefits are clear; increased compliance equals a reduction in brand switching and greater brand loyalty among prescribers and patients. www.JforPC.com

In conclusion As lifespans grow and healthcare budgets shrink, there is no doubt that MDS will become the norm in social and domiciliary care going forward. Were it not for the many myths surrounding intelligent packaging, we may already be seeing the fruits of greater compliance on a wider scale. That said, the medical and caring profession and the patients in their care are reaping the rewards MDS has to offer, and as telehealth takes compliance to the next level, may the healthy innovation continue. Norman Niven is an expert in health and social care, with over 30 years’ experience as a pharmacist, BUPA director, and latterly, as CEO of Protomed and inventor of leading monitored dosage system, Biodose. Norman sits on the board of the Healthcare Compliance Packaging Council (HCPC) and has a keen interest in the role of packaging innovation in improving healthcare outcomes and efficiency. With five patents pending for his flagship innovation, Biodose, Norman continues to design new systems and services to take advantage of pharmacists’ expertise within the healthcare supply chain. References 1. Compliance aids: an elephant in the room, Athwal et al, Pharmaceutical Journal, 22 January 2011 2. Care home error rate of liquid medicine doses four times higher than pills, British Medical Journal, 8 February 2011 3. Monitored dosage systems, otherwise known as multicompartment compliance aids 4. GANFYD (Get A Note From Your Doctor), www.ganfyd.org 5. Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence. NICE 2009 http://www.nice.org.uk/nicemedia/pdf/CG76CostStatement.pdf 6. Compliance aids: an elephant in the room, Athwal et al, Pharmaceutical Journal, 22 January 2011 7. Average Number Of Prescription Items Dispensed To Older People Nearly Doubles In A Decade, UK – Medical News Today, increase in average annual prescriptions dispensed increased from 22.3 to 42.4 in ten years up to 1997 8. Care Home use of Medicines Study (CHUMS), commissioned by DoH, October 2009 9. Richards H, Fortune D, O’Sullivan T, et al. Patients with psoriasis and their compliance with medication. J Am Acad Dermatol. 1999;41(4):581-583 10. Evaluation of the scale, causes and costs of waste medicines, York Health Economics Consortium/School of Pharmacy, University of London, November 2010 Norman Niven is an expert in health and social care, with over 30 years experience as a pharmacist, BUPA director, and latterly, as CEO of Protomed and inventor of leading monitored dosage system, Biodose. Norman sits on the board of the Healthcare Compliance Packaging Council (HCPC) and has a keen interest in the role of packaging innovation in improving healthcare outcomes and efficiency. With five patents pending for his flagship innovation, Biodose, Norman continues to design new systems and services to take advantage of pharmacists’ expertise within the healthcare supply chain. Email: nn@protomed.co.uk

Journal For Patient Compliance Strategies to enhance Health Outcomes 59


Anti-counterfeiting & Brand protection

Fighting Back at Counterfeiters A Q&A with Neil Ivey at Payne Security Payne Security’s brand protection services were recently deployed by a top global pharmaceutical company that fell victim to counterfeit activity. How can pharmaceutical companies identify a breakdown in the supply chain and detect counterfeit products? In the particular case you are referring to, healthcare workers and supply chain staff were working within the company to collect empty product bottles and fill them with combinations of authentic and counterfeit product before reintroducing the counterfeits into the supply chain. As a result, detection was that much harder because the counterfeit activity was actually internal and involved members of staff. Generally, the ability to identify that a product is counterfeit results from basic mistakes made by the counterfeiter; for example something as obvious as a spelling error on packaging is quite common. Counterfeiters spend a lot of money on sophisticated packaging and labels and then simple errors are often overlooked. When working with counterfeit currency, I have seen cases where criminals often spell America incorrectly when they’re counterfeiting a twenty dollar bill. Other indicators can be more subtle. For example, bottle shapes may not be perfectly matched, or the colour shade of a bottle may be slightly incorrect; a simple difference between amber to a light brown. Odours from the pills themselves may also be unusual or the pills may leave an unusually high level of powder residue because they have been formulated incorrectly with the use of chalk. Labels are another key indicator; if a label comes off too easily then this can be a sign of counterfeit activity and will be sent back to a pharmaceutical company for inspection. In order to prevent counterfeit problems, this pharmaceutical company has now implemented your Payne Security tear tape technology. How does tear tape technology work? Is it an overt or covert form of protection? Tear tape functions as a carrier for various forms of technology. Tear tape itself is used throughout the world as an easy-open solution for packaging. If you are a smoker, you will know it as the narrow tape attached on the inner surface of filmic overwrap of a cigarette packet. If you are a non-smoker, you might find it on the package of chewing gum, CD and/or DVD, biscuits, envelopes and other consumer goods. In the healthcare market tear tape is often placed on the shrink sleeve of specific medications, particularly liquid medication. Payne Security’s bespoke tear tape solution can carry a variety of sophisticated brand protection devices, including overt and covert authentication and tamper evidence technologies, as well as security print features. Shrink sleeves in combination with tear tapes offer very obvious and effective overt protection that can be recognised by the consumer and other non-security specialists such as a healthcare worker or pharmacist, as they immediately provide tamper evidence. In addition to this, covert technologies such as taggants can also be placed onto tear tape, with the most effective being 60 Journal For Patient Compliance Strategies to enhance Health Outcomes

completely invisible and only detectable with a special reading device. As with other covert technologies, taggants can only be identified by the brand owner or people they equip with the appropriate knowledge and technology, to provide more conclusive verification. Without the right reader, counterfeiters are unable to locate the position and appearance of the taggant they wish to replicate. Are there any plans to implement tear tape technology into over-the-counter products or is it predominantly concentrated on restricted access drugs such as prescription drugs? It’s definitely available and applicable for over-the-counter products, although it is currently not being used as such. Tear tape technology is very useful for reassuring consumers of the authenticity of the product, because it’s something they can recognise and they can immediately identify if it has been tampered with. What would be the cost incurred by implementing this technology on a wider scale? The per product cost is tiny, and a key advantage of incorporating technologies onto tear tape is that it can be included on packaging without affecting production efficiencies. The majority of these technologies are not that expensive, particularly when you bear in mind that it is an investment into longer tem cost-benefits. By ensuring the security of their products, brand owners are also protecting product revenue and brand reputation. The cost also pales into insignificance when you bear in mind that these security solutions are an investment into ensuring the safety of public health. As a brand protection vendor, what are you doing to get the knowledge out to the consumer that the authenticity of drugs can be identified with your solutions? To fully ensure the success of security products we have to enable consumers to recognise and understand security features and actively participate in fighting counterfeiters. What Payne Security can do to educate consumers is limited by what the brand owners do. The brand owner must communicate through their branding campaign ‘this is what you need to look for and this is how it works’, whether it be a colour shift or a special label. We create the technology and the artwork that illustrates a particular technology, in order to inform and equip the consumer with an understanding of why the security feature is in place and what it does. Consumer education is absolutely vital to brand protection. In your opinion, how would you engage the patient or communicate the measures? With regards to over the counter medication, the measures need to be communicated visibly and the technology needs to be overt; for example, a hologram or specific and identifiable branded packaging that can be used to easily identify a Volume 1 - Issue 1


Anti-counterfeiting & Brand protection

product as produced by a particular pharmaceutical company. Authentication with mobile phones, such as scanning secure barcodes and serialised numbers, is another excellent method for patients to authenticate products. However this is only really applicable for specific regions, as the technology required for this kind of measure is not readily available in all markets How can the right product be implemented into emerging markets where counterfeiting may be even more prevalent, for example, India or China? The key thing here is for the brand owner to understand the problem it is trying to solve and where it is trying to solve it. This is an important question, because the technology that is applicable and beneficial in the US and Western Europe is probably not going to be the same (or useful) in, for example, Africa. Price bands are another factor to consider. Products that are sold in Africa are typically sold at a lower price band than in the US, so it would not be cost-effective for pharmaceutical companies to spend the same amounts of money protecting products released in Africa as they would for products released in the US. Having said that, it is possible for brand owners to deploy technologies tactically in the fight against counterfeiting, so having a clear strategy is key. I think the industry is increasingly moving towards serialisation, i.e. printed coded numbers, which can be packed into a database that can then be interrogated. In the future, dataset technology that can be used as a one on one verification system may also become available. This would involve the use of one number that can be identified against itself, without the use of a comprehensive database that can suffer from inherent security issues. Has Payne Security encountered any challenges where tear tape has been broken or attempts have been made to replicate it? Not in the pharmaceutical industry that we know of. We have seen attempts in other industries, but we have also been able to see marked discrepancies. Our printers can tell the difference between a gravure print and off-set print, but it is unlikely that the average consumer would be able to do this. However, there are other ways for a consumer to tell, for example the taste, or the way it has been purchased — buying products online or from the back of somebody’s car is never a good start! What are the key challenges with regard to online retailing of pharmaceutical drugs? Our general rule with this is, quite simply, don’t buy drugs online. If you do, there is a very high chance that the products will be counterfeit or imitation. None of the pharmaceutical products that we supply security solutions for are sold online.

The most effective brand protection solutions are the ones that are destroyed upon removal from the packaging. A lot of technologies provide the ability to authenticate a product through laser engraving or through security information on a label. Unfortunately, this can often provide a counterfeiter with the opportunity to replicate the solution if they are able to get hold of the label. A tear tape shrink sleeve, however, presents inherent challenges in any attempt to replicate or reassemble labels on the packaging bottle. As a result, this creates a much more significant challenge for the counterfeiter. In addition, if brand owners choose to buy overt technologies such as pigments or holograms online, then to ensure full protection this really needs to be layered with other more covert and specialist solutions. To maximise security I would recommend that brand owners use both overt and covert design features which complement each other and are jointly used on packaging, such as security design and tear tapes. About Payne Security Payne Security (www.payne-security.com) is one of the world’s leading companies in the fields of brand protection, document authentication and personal ID solutions. Overt, covert and forensic technologies can be applied to a wide variety of consumer goods, packaging, national identity documents and tax stamps using inks to lacquers, laminates to labels, tear tapes to threads. Payne Security’s document authentication expertise gives a unique advantage in creating some of the most secure ID card (and other document authentication) solutions. From the latest Magicard ID card printers and sophisticated IDPro7 software to secure smart card production and volume fulfilment, Payne Security is able to meet all personal identification needs. Payne Security (www.payne-security.com) is a part of the Coated & Security Products division of Filtrona plc, the international, market-leading speciality plastic and fibre products supplier. Operating as four companies – Payne, Payne Security, FractureCode & BP Labels – we provide creative and secure packaging, identity and security solutions to our customers and markets of choice and continually invest in our production facilities and quality procedures to ensure the highest standards of manufacture. Coated & Security Products operates from ten sites in eight countries worldwide and employs 371 people. Neil Ivey is the Sales Development Manager, North & South America for Payne Security, a division of Filtrona, PLC. His responsibilities in this role include working with the Private and Public sectors to combat widespread counterfeit issues involving documents and consumer products. Mr. Ivey has been involved applying security solutions for Brand Protection for over 10 years.

What are the key things a brand owner should bear in mind when implementing security solutions? www.JforPC.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 61


Folklore

Uncle Mehmet’s Makat: An amusing example of linguistic and cultural nuances in action At first, they didn’t take it seriously; they said he only had a cold and it would pass. When he got the fever and started to hallucinate it was time to call on Hüsüret Nene from the Old Datça to have her apply Gor, in case he was cursed by the evil eye. When the Gor didn’t help, they called on Uncle Ibiraam to have him try his healing methods, first by wrapping his skin tight, drawing blood and pulling kupa (a cotton ball dipped in alcohol is placed in a cup and lit on fire with a match then quickly turned down on the patients back to shut off the flame. This method is used as a “suction” to pull and release the cold). Then, to regain his strength, Uncle Ibiraam made him drink boar’s blood. When none of it worked, they called upon Gara Omar Nene. She shaved his head, made her special ointment, then rubbed and wrapped it on his head. That night, his fever broke, but only to return in two days. This time they brought in Reshadiye Haci to say his special prayer, that he later wrote on a leaf and rolled so it could hang down on Uncle Mehmet’s neck. This didn’t heal either; nothing happened, nothing changed… The last resort was to see a doctor. In those days there weren’t any doctors in Datça. The nearest island, Sömbeki, was used at one time as an ambulance site for the sick. Unfortunately, this wasn’t an option for Uncle Mehmet due to changed rules and regulations. Uncle Mehmet’s relatives and neighbours recommended seeing a doctor in Izmir. The next day at the crack of dawn, accompanied by his wife Imine, he headed out on his journey. Catching the first jeep out of Marmaris, they arrived in Mugla and slept at the Yagcilar Inn. The next morning they got two seats on the bus and traveled to Izmir. That evening they spent the night at the Akdeniz Hotel, where all the travelers from Datça stayed. In the morning, after having their breakfast, they took out the recommended doctor’s address and set out to see him. After a long visit and examination, the doctor wrote a prescription and handed it to Uncle Mehmet, telling him: “Tonight, before you get to bed you’ll need to insert one in the makat. I wrote the prescription for ten suppositories; apply one every other day. When you’re finished, and if you’re still not feeling well, I want you to come back and see me again. Is that understood, Uncle Mehmet?” Uncle Mehmet signalled “yes” to the doctor by shaking his head. He paid and left the doctor’s office with his wife at his side. They were both very happy that the application of the medicine was an easy one. Uncle Mehmet was always very fearful of needles. Actually, that was one of the reasons for delaying doctor visits all these years. Relieved that he didn’t have to swallow a pill or get an injection, he said, “Oh my - this was easy! Every night before bed, I’ll put one suppository in the makat and go to sleep - no fear of needles or pills! Really, our neighbours recommended a great doctor!” They entered the first pharmacy they sighted, purchased the suppositories, and walked over to the garage terminal. In those days the buses that travelled between small towns were stationed in a garage in Basmane. They looked for a 62 Journal For Patient Compliance Strategies to enhance Health Outcomes

bus to take them to Mugla, but because it was late in the day there weren’t any buses going to Mugla. Instead, they found one to Aydin which was scheduled to depart in the next two hours. Even though it was going to be a hassle to find a bus to Mugla after arriving at Aydin, they agreed to purchase their bus tickets. Well! A traveller must be on his way, they both thought. While waiting, they decided to stop for dinner at an affordable Basmane restaurant. After filling their tummies they returned to the garage, got into their waiting bus and situated themselves in their seats. They both looked around to see if there were any familiar faces from Datça. Being away these couple of days they realized how much they had missed Datça, but with the moving of the tyres, they felt as if their wings had lifted and they were flying towards Datça. They were so excited… When the sun was about to set they arrived in Aydin. Knowing that they would have to spend the night, they started walking towards the Mugla Hotel, which was located next to the terminal. Suddenly, they heard a man yelling, “To Mugla, to Mugla!” It was the Jeep chauffeur, and it was their lucky day everything was flowing so smoothly. Instead of checking into the hotel, they got their seats in the Jeep and arrived in Mugla early next morning. In another two hours they needed to catch the Jeep bound for Marmaris. Upon their arrival in Marmaris in the late afternoon, they realised the Jeep to Datça had already left. They weren’t keen on spending yet another evening in Marmaris, but there wasn’t much choice. By God, this was better than before; they were thankful, and realised that they had no reason to complain. Besides, there was now a once-a-day Jeep service between Marmaris and Datça. The ride was scheduled to leave the next afternoon at 13:00 hour. That meant that they would travel during the heat of the day and would arrive in Datça in the evening. Anyhow, they would patiently wait to catch the next day’s Jeep ride, so they spent the night at Çavus’ Inn. The next day, they squeezed into the jeep traveling to Marmaris, cooped up with at least ten other people. Once on the road to Datça, they no longer noticed the dust of the road or the discomfort of being with all these passengers. They were happy as long as they were getting closer to Datça… When they arrived at Resadiye the sun had just set. They ate their evening meal of soup and salad and felt so tired they decided to retire. Before bed, according to the doctor’s order they had to place the suppository in the makat. Uncle Mehmet called on his wife who was washing the dishes on the front of the house: “Where the heck is our makat?” Imine came to the door with both wet hands opened upward on her side and showed him to the storage closet: “Look, there, it’s on top of the kilim do I need to point it to you?” He slowly left the couch where he was sitting and walked over to the closet. Yes, he could see the box on top of the kilim! When he opened the box he was able to see the colorful suppositories gleaming at him. “Okay, okay - don’t get worked up; I see it!” he said. He carefully took one, lifted the makat and placed the suppository between the folds. Then he went to bed. As he lay his head Volume 1 - Issue 1


Folklore

Historically this was the old center of Datça

down, he felt he had accomplished the task of entering his first day in the therapy. The next day Uncle Mehmet stayed home from work. In his place, his wife Imine went to the fields and took care of the chores as much as she could. While Uncle Mehmet was in therapy, he pretty much did the same every day for the following twenty days: relaxing at home, then before bed, taking a suppository from the box and placing it between the makat. At the end of the twentieth day, when there were no more suppositories left in the box, Uncle Mehmet realised his condition had worsened instead of getting better. That’s when he remembered the doctor’s instruction telling him to return to the office in case he hadn’t seen progress. That night during dinner, he asked his wife: “So, what do you say, Imine; these suppositories didn’t work - should we go back to see the doctor?” “Sure, you know best,” replied Imine. That night, they started the preparations for the next day’s road trip to Izmir. They gathered foods such as cheese, olives and boiled eggs, and packed them in a cloth for their journey. Before heading out, he gathered the suppositories stashed away in the makat, securing them in a tightly-tied clean hanky. Once again at dawn they hopped on to the Jeep and travelled to Marmaris. That night they spent the evening in Mugla. By the next evening they were in Izmir, and like all the other Datça travelers they stayed at the Akdeniz Hotel. The plan was to rise early morning and go to wait on the doctor’s doorstep. When the doctor arrived at his office that morning, he found the couple sitting on the steps. Because they were the first to arrive, they automatically got the first appointment of the day. The doctor remembered Uncle Mehmet and welcomed him into his office, offering him a seat and asking: “So, Uncle Mehmet, tell me - how have you been feeling?” Uncle Mehmet opened up the tightly-knotted hanky and placed all the suppositories on the doctor’s desk. “Here,” he said, “just like you ordered, I followed your directions and put these in the makat every day for twenty days, but still I am not better. Look; I have them all here…” The doctor hadn’t quite understood what he meant, especially when the suppositories looked untouched, new and still shiny in their packaging. The doctor was puzzled - they didn’t look as if they had been inserted in the makat. To make sure, the doctor asked Uncle Mehmet again: “Tell me from the beginning again how you applied these to the makat untouched, and were able to remove them again looking unused?”

Uncle Mehmet looked at him, also with a puzzled look on his face! What was the big deal about placing and removing the suppositories in the makat??? Where was the smart doctor that they were all talking about! “Mister Doctor, what is the big deal? Our makat is in the closet along with the other kilims. All I had to was to open the fold and insert one in every night.” Now, the doctor knew that Uncle Mehmet had confused the meaning, so he asked again: “Tell me, Uncle Mehmet, what you really mean by saying ‘makat’?” “Well, Mister Doctor, weren’t you the one who told me to apply it to the makat? In our house, all the kilims and makats are in the same closet. So, as instructed, I got the makat, opened the fold and placed the suppository in!” That’s when the doctor knew that in the Datça dialect the word “makat” meant a different sort of a kilim, whereas in the real meaning of the Turkish language it meant the anus. The doctor couldn’t stop himself from laughing, which caused his eyes to tear. Anxiety-stricken Uncle Mehmet had no energy left in him to laugh. He was overwhelmed by the difference between the two meanings, embarrassed for his lack of education, and even more horrified when the doctor pulled him behind the screen and demonstrated the application of the first dose from the other end, and not the mouth. He had made the trip to Izmir twice and God knows if he hadn’t brought the suppositories along, he would’ve done the same thing again! When he appeared again from behind the screen, the sweat was trickling down his forehead. He was not able to look his wife in the face. Concerned, she asked: “What’s wrong? What happened, Mehmet?” “Don’t be silly, and hold your tongue, woman!” he said, angered. Hunched over, he walked to the chair and picked up his jacket. With his wife following him, in a faint voice he waved “Good day…” to the doctor and exited the office down the steps to the street, in a mix of human emotions… Tribute to Nijat Akkaraca: Nijat passed away in 2009. He was a highly regarded historian and author from Datça, Turkey. Nijat founded the Datça Local History Group, and through this group he played a key role in documenting oral histories that would otherwise be lost. He recorded many stories connected with the Datça region, and about life in Old Datça when the village had a strong Greek community. Working with Nick Halkitis (Global eMarketing Director at MediciGlobal) Nijat Akkaraca and Nick Halkitis jointly created Peace Day to strengthen ties between Datça, Turkey and Symi, Greece. The two established an annual World Peace Day Swim that has swimmers from both countries swim to greet each other. It has been said that Akkaraca believed that “Greeks and Turks were two halves of the same apple.” Thanks: To Arlene Dekrikorian of MediciGlobal for translating Nijat’s story into English.

Footnote: The name ‘kilim’ or ‘kelim’ is Turkish, and comes from the Persian gelim ( ) ‘to spread roughly’, which is probably of Mongolian origin. Various forms of the word are used in the Balkan languages ( ). Not only were pile carpets produced in ancient times, but also kilims.Kilims are produced by tightly interweaving the warp (vertical strands) and weft (horizontal strands) of the weave to produce a flat surface with no pile As kilims are much less durable than rugs that have a pile to protect the warp and weft, it is not surprising that few of great age remain. www.JforPC.com

Journal For Patient Compliance Strategies to enhance Health Outcomes 63


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