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Volume 2 - Issue 1

✓ PATIENT COMPLIANCE Strategies to enhance Adherence and Health Outcomes The Moral Imperative of Improving Patient Adherence To Pharmacotherapy for Cardiodiabesity A Focus on Type 2 Diabetes Mellitus – Part 1


Chronic Respiratory Diseases And their Challenges A Novel Approach to Improving Patient Adherence Collaboration Across Healthcare Industry Silos

Patient Communities The Future of Adherence?





Strategies to enhance Adherence and Health Outcomes

A Patient Story

DIRECTORS Martin Wright

8 Dentist Murray Hawkins talks about Dental Anxiety The dental industry and profession is renowned for its innovation in materials science, equipment design and advancement of technique. It is surprising therefore that this most basic of dental procedures – local anaesthetic delivery – remains firmly in the “dark ages”. It is arguably for this reason that fear of the needle and fear of injections appear to be at the heart of dental anxiety and phobia. In this article Dr Murray Hawkins looks into the psycho-social factors which act as barriers to accessing dental care, and the solutions to overcome dental anxiety.

PUBLISHER Mark A. Barker MANAGING EDITOR Mark A. Barker EDITORIAL COORDINATOR Jaypreet Dhillon EDITORIAL ASSISTANTS Nick Love, Kevin Cross, Lanny McEnzie DESIGN DIRECTOR Ricky Elizabeth RESEARCH & CIRCULATION MANAGER Dorothy Brooks BUSINESS DEVELOPMENT Kristine Saunders ADMINISTRATOR Petya Stefanova FRONT COVER © iStockphoto PUBLISHED BY Pharma Publications Unit 7a, Evelyn Court Grinstead Road London SE8 5AD Tel: +44 0208 6922878 Fax: +0014802475316 Email: Journal For Patient Compliance – Strategies to enhance Adherence and 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. 2012 PHARMA PUBLICATIONS Volume 2 issue 1

10 Patient Advocacy: Compliance from the Patient’s Point of View Frequently patients go through a medical crisis or event which causes them to require medication. Many physicians, clinicians and pharma lay the blame for non-compliance squarely at the feet of the patient. However, in most cases this is simply not true. Jacqueline O’Doherty from My Healthcare Connect discusses the major barriers to compliance are the cost of the medication, followed by education, misinformation, medication coordination and reconciliation, as well as procrastination and forgetfulness. Watch Pages 12 Packaging & Patient Adherence There have been a number of exciting developments in the areas of leading-edge Drug Delivery, Drug Packaging, and Labelling & Dispensing, some of which have involved the internet and its interface with emerging technology, and others of a more simple and traditional nature. This has occurred against the backdrop of a non-adherence problem that has escalated over the years. According to a compliance-monitoring database, every day 10% of those who are engaged with their therapy forget to take their medicine. Chris Penfold from Design Cognition provides an overview of how we can improve existing treatments to ensure greater adherence. 14 An Expert Viewpoint: Building an Adherence Trust Pathway While electronic monitoring of patients’ medicines adherence is becoming standard practice in clinical trials involving chronic diseases, most patients are left to their own devices outside of the controlled environment. This is why it is important that we do not lose sight of the impact HCPs have when it comes to motivating and supporting patients throughout their treatment. Carole North, co-founder of 90TEN Healthcare, describes the framework and knowledge of new technologies to inform the market research among HCPs and patients. 16 The Role of Co-Pay Card Programmes in Medication Adherence In countries where cost is not an issue given socialised medicine, the overall adherence rate is not much better than in the US. Pharma marketers focus on increasing market share through patient acquisition and use co-pay cards to encourage patients to fill their brand prescriptions. Moreover, pharma manufacturers are looking for additional strategies that encourage physicians Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 1

Contents to prescribe their product. Marc Migliorini, Senior Director of Marketing for OPUS Health, explains that there are numerous strategies that can get the new therapy established with prescribers while encouraging patients to refill their medications. 18 The HCPC Alliance Awards Innovative Packaging for Better Patient Compliance Over the last years the lament of the pharma industry over the lack of new blockbuster drugs has become increasingly louder, and we hear more and more of companies laying off hundreds or even thousands of their staff. At the same time we hear of governments being forced to cut their budgets, and healthcare is one of the areas of top priority to reduce costs. Whenever the financial aspects of a system come under scrutiny, one should look at its efficiency and its effectiveness. Tassilo Korab, co-founder of HCPC-Europe, explains how the Healthcare Compliance Packaging Council in the US and HCPC-Europe have been fighting for decades to raise awareness of the role packaging plays in patients’ decision-making whether or not to be and/or stay adherent/compliant. 20 Medication Non-Adherence and the Public Opinion Problem The adherence problem is finally evolving from the biggest problem in healthcare you probably didn’t know about, to one with at least some degree of public recognition. Although coverage of the topic is not yet on a par with coverage of, say, the rise in obesity, the dangers of a sedentary lifestyle, or other similarly significant behavioural health crises, it is now — at least — on the national radar. Dr Katrina Firlik, co-founder of HealthPrize Technologies, discusses how the effort to inform the public of the serious consequences of medication non-adherence is met not with a “wow, that’s a real problem” but more often with a snide “Ha!” Regulatory & Market Place 22 Evolving US Safety Regulations and Risk Management Programmes The US Risk Evaluation and Mitigation Strategies (REMS) requirements for a drug or drug class are continuously evolving. The FDA solicits feedback and collaborates with pharmaceutical companies in an effort to find the right balance between patient risks and benefits. Jean Steckler, Senior Vice President & CoFounder of iReminder, looks into how much of the REMS design has evolved from earlier work on risk management programmes and RiskMAPs. 26 Patient Communities: The Future of Adherence? Pharma companies will succeed or fail based not on how much drug they sell, but on how well their market offerings improve outcomes. Essentially, intentional non-adherence derives from the balance between patients’ perceptions of whether or not they actually need to follow a prescribed regimen, and their concerns about following it. James Kelway, User Experience Director at Hello Group, looks into the reason for the gap between patients’ desire for knowledge and their false perceptions of their regimens, which may lie in the current realities of healthcare systems.

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Behaviour Programmes 30 Whose Health Literate? During the first half of 2012 the European Council and Parliament will debate the Commission’s new proposals for updating the directive on information to patients on medicines. To truly help the majority, programmes need to be put into place to effectively communicate with the majority of patients. Ian De’Ath, Partner and Director at Wizzard, provides an overview of how it is left to the industry to pick up the pieces and create programmes that will improve the health literacy of patients and through that, improve adherence. Clinical Trials 32 The Moral Imperative of Improving Patient Adherence to Pharmacotherapy for Cardiodiabesity, Part I: A Focus on Type 2 Diabetes Mellitus While the term cardiodiabesity has not currently gained the same traction as some other terms that have recently entered the biomedical lexicon, it effectively captures three chronic and interrelated diseases of enormous relevance to global public health: obesity, diabetes, and heart disease. One aspect of addressing these diseases is improving patient adherence to prescribed pharmacotherapy regimens: it is a global public health moral imperative. J. Rick Turner, Senior Scientific Director, Integrated & Translational Cardiovascular Safety at Quintiles, focuses on type 2 diabetes mellitus (T2DM), and provides what is hoped might be provocative suggestions that will lead to pragmatic progress. 38 The Role of Home Visits in Clinical Trials Participating in a clinical trial can be a significant undertaking for a patient. Depending upon the nature of their condition and the length of the trial, enrolling in a study can mean a large commitment, timewise, emotionally and financially. Ruth Smith, Clinical Operations Manager at Research Nurses, explains how once patients have been identified, it is beneficial to all parties to ensure that the study design is such that it is advantageous to the patient, aiding both recruitment and retention. Therapeutic 42 Chronic Respiratory Diseases and their Challenges The WHO estimates that hundreds of millions of people suffer every day from chronic respiratory diseases. Their last estimate revealed that approximately 235 million people have asthma, 64 million people have chronic obstructive pulmonary disease (COPD), and millions of others have allergic rhinitis and other chronic respiratory diseases worldwide. This article by Kathrin Heinritz of Pharmexx Group focuses on Asthma and COPD, since they represent the biggest proportion of respiratory diseases. She explains the reasons for non-adherence for a chronic disease of which the symptoms can be effectively treated, and which does not entail a difficult or harmful administration of the medication.

Volume 2 - Issue 1

Contents Modern Technology


44 Will Advances in Technology Continue to Change the Everevolving Patient Adherence Landscape? The increasing influence of smart technology to help doctors track patient adherence continues to gather pace as the industry looks ahead. The technology to collect accurate data faster, and to make data more easily available, is there. Perhaps what is slightly less advanced and a challenge for pharmaceutical companies is how to report and use the data to improve clinical decisions and trigger remote care to patients. Charlie Inglefield of Partizan International discusses what smart technology can do for you as the pharma marketer.

50 Because Patients Know Best… The digital revolution has opened the door, enabling pharma to really get involved in what therapy benefits really look like to their patients and healthcare professionals. In recent years, the quest for payer approval in a rocky economy has been one of the most challenging journeys. Proving patients are realising the benefits of a given therapy has become part of the solution to this challenge. However as formalised qualitative systems, cost-cutting measures take priority and as a consequence pharma companies are missing the whole point of what it means to be patient-centric. Laura Barnwell of Eye For Pharma discusses the unique concept of going directly to the patients themselves to find out what patient benefits really are, putting them in the driving seat to tell pharma exactly what outcomes really make a difference to them.

46 Polymedication Electronic Monitoring System (POEMS) – Introducing a New Technology as Gold Standard for Compliance Measurement Non-compliance is no longer simply the failure of the patient to follow the physician’s advice. The phenomenon is complex, its occurrence is random, it is affected by multiple factors, its predictability is difficult and its public policy implications have been debated over the past decades. Traditional indirect measures like self-reporting, medication diaries, residual pill counting, pharmacy records, clinician opinion (i.e. which do not demonstrate drug ingestion) satisfy many criteria. Isabelle Arnet & Kurt E. Hersberger from the Department of Pharmaceutical Sciences, Pharmaceutical Care Research Group, University of Basel present a new technology of electronic adherence measurement of oral solid forms, and describe its advantages compared to the electronic devices currently in use. Drug Delivery, Drug Packaging, Labelling & Dispensing 48 Label Solutions Helping to Improve Patient Compliance The development and delivery of healthcare products is a costly business, so it stands to reason that every effort should be made to ensure products are used in the correct manner by the patient or end-user. Besides the initial contact a patient will have with a doctor and the pharmacist, the only further communication they may have is the packaging and labelling. Given the huge cost of developing, testing and launching a new drug, it would be a false economy to use cheaper and potentially less effective packaging if it might limit patient compliance, and therefore the effectiveness of the drug. Stephen Moor of Fix-A-Form International discusses how leaflet labels are a tried and tested method of helping to improve communication with the end-user.

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54 A Novel Approach to Improving Patient Adherence: Collaboration Across Healthcare Industry Silos We’re all patients. We’re all customers. At times we’re all nonadherent or non-compliant, and we don’t like to be referred to as either. We want to look back at our own experiences to discuss what kind of help, reminders or systems might nudge us to better health behaviours and better health. Dyan Bryson of Inspired Health Strategies discusses the formation of the Patient Adherence Working Group, with the intention of engaging interested stakeholders in conversation and working to see how everyone can understand, and take action on, the goal of having patients take their medication and embark on good-health behaviours for the benefit of all concerned. 56 Five Principles for Designing Effective Patient Communication Programmes Patients, who now spend less face-to-face time with their doctors, increasingly seek out independent sources of information about their disease states and potential treatments. For their part, busy physicians want objective sources of information that their patients can easily access and understand. Adam Bianchi, Chief Operating Officer, and Eric Bolesh, Director of Research, of Cutting Edge discuss the five principles from the findings of their recent study of patient communication programmes. Within the article, participating executives shared their strategies, goals, tools, performance metrics and expectations for the future.

Volume 2 - Issue 1

Foreword Low compliance to prescribed medical interventions is an ever-present and complex problem, especially for patients with a chronic illness. With increasing numbers of medications shown to do more good than harm when taken as prescribed, low compliance is a major problem in healthcare. Patient adherence – the degree to which patients follow the recommendations of their health professionals – is a salient outcome of the process of care. Across many disease conditions, non-adherence to prevention and disease management activities (e.g., medications, appointments, screening, exercise, and diet) averages 25% of patients; for some medical conditions and in some settings, adherence can be as poor as 50% or less. The World Health Organization proposes that adherence is affected by these factors: 1) healthcare system or providerpatient relationship, 2) disease, 3) treatment, 4) patient characteristics, and 5) socioeconomic factors. In a review of the literature from 1948 to 2001, 122 studies were found that correlated structural or functional social support with patient adherence to medical regimens. Meta-analyses establish significant average r-effect sizes between adherence and practical, emotional, and unidimensional social support; family cohesiveness and conflict; marital status; and living arrangement of adults. Substantive and methodological variables moderate these effects. Practical support bears the highest correlation with adherence. Adherence is 1.74 times higher in patients from cohesive families, and 1.53 times lower in patients from families in conflict. Marital status and living with another person (for adults) increase adherence modestly. Physician communication is significantly positively correlated with patient adherence; there is a 19% higher risk of non-adherence among patients whose physician communicates poorly than among patients whose physician communicates well. Training physicians in communication skills results in substantial and significant improvements in patient adherence, such that with physician communication training, the odds of patient adherence are 1.62 times higher than when a physician receives no training. Adherence is significantly also positively correlated with patients’ beliefs in the severity of the disease to be prevented or treated (disease threat). Better patient adherence is associated with objectively poorer health only for patients experiencing disease conditions lower in seriousness (according to the Seriousness of Illness Rating Scale). Among conditions higher in seriousness, worse adherence is associated with objectively poorer health. When I decided to publish the Journal for Patient Compliance, my ultimate goal was to bring out a comprehensive guide for healthcare professionals to source the best methods of achieving better patient adherence. In this issue we have brought you another set of very practical guidelines. Carole North, co-founder of 90TEN Healthcare, describes the framework and knowledge of new technologies to inform the market research among HCPs and patients (page 14). The Role of Co-Pay Card Programmes in Medication Adherence is explained by Marc Migliorini of OPUS Health (page 16). J. Rick Turner of Quintiles focuses on type 2 diabetes mellitus (T2DM), and provides what is hoped might be provocative suggestions that will lead to pragmatic progress (page 32). Kathrin Heinritz of Pharmexx Group focuses on Asthma and COPD, and explains the reasons for non-adherence for chronic disease states (page 42). I hope you all enjoy this issue of the Journal, and look forward to meeting you next time. Mark A. Barker 6 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

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 Carole North, Managing Director, 90 TEN Healthcare Dyan Bryson, Managing Partner/VP Patient Strategy & Outcomes for Inspired Health Strategies 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 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

Volume 2 - Issue 1

Patient Story

Dentist Murray Hawkins Talks about Dental Anxiety As far as dentistry is concerned, the population is divided into two camps: those who visit the dentist, whether infrequently or routinely, and those who never do. The number of people registered with dentists in the UK is approximately 31 million, or only 52 per cent of the population.1 Reflecting a continuing improvement in adult dental health, the most recent Adult Dental Health Survey (2009)2 found dental decay (caries) having a reduction from 46 per cent to 28 per cent since 1998: this is primarily attributed to the availability of fluoride in drinking water, toothpaste, mouthwash and topical gels; however, the larger issue of periodontal disease remains. The Survey highlights that 83 per cent of dentate adults showed some evidence of periodontal disease (that is bleeding, calculus, periodontal pocketing of 4mm or more) and, in the case of adults aged 55 or over, loss of periodontal attachment of 4mm or more anywhere in their mouth. As all dental professionals are aware, left untreated this can lead to pus-filled pockets and loss of attachment resulting in gingival retreat and recession. This fact will come as no surprise to many dental professionals who face an ongoing challenge encouraging their patients to maintain good plaque control. Data shows that a carefully supervised plaque management control programme can minimise periodontal disease.3 Studies also demonstrate that if plaque is allowed to proliferate and mature without the implementation of any oral hygiene routine, gingivitis will develop within two to three weeks.4,5 Oral hygiene instruction is a fundamental cornerstone of the dentist/hygienist-patient relationship and it is surely no overstatement to say that patient compliance with oral hygiene advice is one of the biggest challenges faced by dental teams today. But it’s not the only challenge. How can the 48 per cent of the UK population who are not registered with a dentist,1 or who have never received dental treatment, be helped? According to Ruth Freeman, published in the peer-reviewed British Dental Journal, there are four psycho-social factors which act as barriers to accessing dental care: sycho-social factors which act as barriers to accessing P dental care • Dental anxiety states • Financial costs • Perceptions of need • Lack of access British Dental Journal, Volume 187, No. 3, August 14 1999 Of these, dental anxiety6,7 has been highlighted as being one of the most important barriers with regard to dental attendance. So how common is dental anxiety? The 2009 Adult Dental 8 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Health Survey found that 28 per cent of adults have dental phobia, and a further 41 per cent have dental anxiety. For adults who are dentally anxious,8,9 it is the pain associated with the drill and the local anaesthetic injection which is the most feared aspect of dental treatment. It is estimated that there are approximately 70 million local dental anaesthetic injections administered annually in the UK.10 The vast majority of these injections are delivered by the traditional syringe, which has largely remained unchanged since its introduction to medicine and dentistry in the mid-1800s. The dental industry and profession is renowned for its innovation in materials science, equipment design and advancement of technique. It is surprising therefore that this most basic of dental procedures – local anaesthetic delivery – remains firmly in the “dark ages”. And it is arguably for this reason that fear of the needle and fear of injections appears to be at the heart of dental anxiety and phobia. How I Address the Problem of Dental Anxiety As a practitioner running a private practice I am always conscious of the fact that patients naturally expect that bit more from a practice when they are paying for private treatment options. Most patients believe that a modernlooking practice with pristine surgery rooms, state-of-the-art equipment and a wide range of treatment options delivered by friendly, caring clinicians is to be expected from the private practice. In my experience, patients also expect that they’ll be given more time for consultation and for their treatment to be provided in a relaxed and unhurried manner. But it could go wrong if we don’t make patient comfort the priority. I’ve found that putting patient comfort first has been an essential step in building lasing relationships with my patients, and by their word of mouth we have attracted many new patients. The ‘more comfortable experience’ has been proven to build patient trust, loyalty and long-term practice development. And at the heart of this is the virtually painless local anaesthetic injection. My decision, nearly ten years ago, to invest in Vibraject technology was based on my own experience of the anxiety issues and my conviction that really good injection technique really can highlight the difference in private dentistry. How does Vibraject Work? Vibraject is a device that’s new to the UK but has over 15,000 users in the USA. It’s a small battery-powered unit which simply clips onto the syringe barrel. There are no consumables other than the battery. It causes the needle to vibrate and this vibration is transmitted to the nerves which sense pressure and vibration. These nerve fibres respond, transmitting their signals to the brain faster than the pain signals caused by the injection which are transmitted on thinner, more poorly Volume 2 - Issue 1

Patient Story

insulated fibres. The patient only experiences soft vibration, putting them completely at ease even during the most potentially painful palatal injection. Vibraject works because its effectiveness aligns with the Gate Control Theory of Pain Mechanisms introduced by psychologists Ronald Melzack and Patrick Wall.11 In short, the theory is based upon the finding that sensations of pressure and vibration successfully compete with sensations of pain for transmission to the brain (clinicians who apply pressure to the injection site prior to injection will be familiar with this effect). So the vibrations essentially mask your patients’ discomfort during local injections. I have calculated that I have given over 27,000 injections using Vibraject in the past ten years. My patients’ reactions have been surprising and rewarding. They hear the buzzing sound, they feel the vibration but they do not feel the injection. They say things like, “That’s much better than when you used to give injections!” I wouldn’t claim that Vibraject overcomes the pain associated with poor injection technique - it doesn’t - but it is an amazing adjunct to a good injection technique. By this I mean: a calm and relaxed manner, a topical anaesthetic, a super-sharp bevelled needle, a warmed cartridge, slow anaesthetic delivery infiltration and the Vibraject. Then the injection is virtually undetectable to patients. How does Vibraject Compare with Other ‘Pain-free’ Injection Technologies? There are other devices on the market that address the issue of patient fear and painful injections. The Wand (Milestone Scientific, has been around for some time. It consists of a microprocessor that automatically compensates for different tissue densities, delivering the anaesthetic at a constant pressure. It has a lightweight, non-threatening, disposable handpiece in which the needle is fitted allowing a pen-like grasp. A foot pump controls the flow rate of anaesthetic. The system uses standard dental local anaesthetic cartridges. The Wand costs c. £2600 + VAT. Single use Wand handpieces cost £2.50 each. The Quicksleeper system ( has been developed over the past ten years and claims to provide virtually pain-free local infiltration and intra-osseous anaesthesia. It utilises a simple clinical pen-grip injection technique and is able to anaesthetise two to eight teeth with one injection. The Quicksleeper costs c. £2695 + VAT. I use the Vibraject because it works and because it costs only £299 – that’s less than the VAT on the Wand! I would recommend it to all clinicians who give local anaesthetic injections. But don’t just take my word for it. Dr Philip Lewis, who

runs a private practice on the Isle of Wight, has also used Vibraject for over 10 years. He says “I’ve always been interested in anaesthetic techniques and making them as comfortable as possible for the patient. And in my cupboard I have electronic anaesthesia going back to the 1980s – we’ve got some intra-osseous systems, we’ve got intra-ligamental systems – and they’re all upstairs in the cupboard. It’s only the Vibraject that gets used, all the time, for every injection, and has been for a number of years.” References 2. UK Adult Dental Health Survey 2009 3. Axelsson P & Lindhe J (1987) J Clin Periodontology 1987; 14:205-12 4. Löe H et al. (1965) J Clin Periodontology 1965; 36:177-187 5. Theilade E et al. (1966) J Periodontal Research 1966; 1:1-13 6. Adams EK, Freeman R, Gelbier, Gibson BJ (1997) Accessing primary dental care in three inner city boroughs. Comm Dent Health 1997; 14:108-112 7. Vassend O (1993) Anxiety, pain and discomfort associated with dental treatment. Behav Res Ther 1993; 31:659-666 8. Moore R, Brodsgaard I (2001) Dentists’ perceived stress and its relation to perceptions about anxious patients. Community Dent Oral Epidemiol 2001; 29:73-80 9. Kleinknecht RA, Klepac RK, Alexander D (1973) Origins and characteristics of dental fears of dentistry. Journal of the American Dental Association 1973; 86:842-848 10. Cawson RA, Curson I, Whittington DR (1983) The hazards of dental local anaesthetics. Br Dent J 1983; 154:253-258 11. Melzack R, Wall P (1965) The gate control theory of pain mechanisms. Science 1965 Nov ID; 150(699): 971-97 Dr Murray Hawkins DGDP (UK) BDS owns the Winning Smiles Dental Practice in Gillingham, Dorset. His special interests are preventive and cosmetic dentistry, but foremost is his commitment to nervous and phobic patients. Murray himself is a winner of the Britain’s Dentist of the Year Award in 2002, and he was a finalist in the 2009 Smile Awards for Excellence in Cosmetic Dentistry. A committed user of Vibraject technology for routine LA injections since 2002 when he read Gordon Christensen’s positive CRA report on Vibraject, Murray decided in 2011 to bring this product to the UK and formed Vibraject UK Ltd, based at his Dorset practice. Email: Tel: 01747 826222. Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 9

Patient Story

Patient Advocacy: Compliance from the Patient’s Point of View Many physicians, clinicians and pharma lay the blame for non-compliance squarely at the feet of the patient. However, in most cases this is simply not true. There are many other barriers to compliance, which we will explore here. A major barrier to compliance is the cost of the medication, followed by education, misinformation, medication coordination and reconciliation, as well as procrastination and forgetfulness. Frequently patients go through a medical crisis or event, which causes them to require medication. Usually this is not budgeted for, so the accompanying medical protocol can be financially daunting. For most patients the cost of their medication comes out of discretionary income. For those whose budget is very limited and already stretched thin, the affordability of the meds poses a severe obstacle to adherence. When finances are constrained, the patient is tempted to cut back or completely discontinue the medication entirely. (It didn’t help that President Bush totally caved to big pharma – talk about a handout – when Medicare D was implemented.) The pharmaceutical companies need to address the financial issues by focusing more on outreach and education, implementing and informing patients how to access and apply for discount medication programmes. Another disincentive to proper medical adherence is increased co-pays; when the co-pay is increased, compliance decreases. Benefit managers at large companies are beginning to learn the value of keeping the co-pay low as they see the resulting long-term saving to the company. This is another area where much more education is needed. Physicians are another key factor to driving compliance. Physicians must invest the time to have a frank, thorough discussion with the patient and a second person (care-giver, advocate) in simple plain language so the patient and caregiver completely understand what the medication is, why they are taking it, and what kind of symptom improvement and/ or side-effects to look for. The patient should reiterate the information back to the physician, to ensure understanding and improve retention. For example, a patient will complete the first round of medication, but feel fine or see no measurable difference – and because of the lack of education, will fail to renew the script and will discontinue the medication. Or the meds made them nauseous, so that again due to the failure of the physician to communicate and inform, the patient becomes non-adherent. That’s the doc’s fault, not the patient’s! Clear, concise, plain language goes a long way in driving adherence. Along with physicians, the pharmacists also have a responsibility when it comes to patient adherence. First and foremost, every single time a new med is added, the pharmacist needs to do a medical reconciliation… every single time! The physician should be doing medication management and medication reconciliation at every appointment. Both the physician and the pharmacist must always review medication across all specialities and interactions with any over-the10 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

counter drugs and supplements. Also the patient’s individual needs and concerns have to be taken into account and understood. Working with the patients taking a collaborative, not paternalist approach allows the patient to become empowered and enhances compliance and adherence. Other barriers to adherence include difficulty swallowing the drug. Is the drug scored? Can the patient cut the drug? This is a chief concern for the elderly. Does the patient understand how to use/administer medication … inhaler, insulin shots? Print the package insert (PI) in simple, clear language. Legally the current PI will never go away, but the drug companies should add a second PI aimed exclusively at the consumer, with plain, concise, simple, easily-understood language and drawings. Another important barrier to adherence is patient procrastination and forgetfulness. Procrastination can be easily overcome, with home delivery programmes, automatic refills, and the use of only one pharmacy (also important for medication reconciliation). Forgetfulness can be addressed in many ways. There is the use of medication forms and pill boxes. Very often a family member or care-giver will fill the box and remind the patient to take the meds. Case managers and home health aides can also oversee adherence. In addition, technology has given us are many new and improved pilldispensing devices, some with audible reminders. Others will call or email the client to remind them to take the medication, and if the medication is still not taken, a care-giver will be notified. There is some controversy with the notification of the care-giver; some feel it is too much like “big brother is watching”. On the other hand, knowing your loved one is taking the correct medication, on the correct schedule, gives invaluable peace of mind. Peace of mind and compliance; you can’t beat that! When the patient’s needs and concerns are validated and addressed, adherence and compliance will follow, which results in improved outcomes for all. Jacqueline O’Doherty of Health Care Connect, LLC is an experienced certified Patient Advocate who guides patients through the complex healthcare system. As a Patient Advocate, Jackie supports and empowers patients and their families, ensuring the patient is aware of all their options, by researching illness and disease, coordinating patient care and facilitating communication and continuity among all the healthcare providers. Jacqueline navigates the healthcare system with patients and their families, throughout the medical continuum, ensuring patient centered care and protecting the patient’s healthcare rights. For further information please contact Health Care Connect, LLC Phone: 908-781-2401 Email: Website: Volume 2 - Issue 1

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Packaging & Patient Adherence Hello and welcome to 2012. Since I last wrote in the Journal for Patient Compliance there have been a number of exciting developments in the areas of leading-edge drug delivery, drug packaging, and labelling & dispensing, some that have involved the internet and its interface with emerging technology, and others of a more simple and traditional nature. This has occurred over the backdrop of a non-adherence problem that has escalated, highlighted in a recent issue of the American Heart Journal, which provided details of the outcome of a recent think tank meeting at the Duke Clinical Research Institute that reviewed the magnitude, prevalence, impact, and cost of medication non-adherence. They stated that “Poor medication adherence is a growing national concern. Research shows that half of all patients in the U.S. do not take their medicines as prescribed, despite evidence that medical therapy prevents death and improves quality of life. Approximately 125,000 deaths per year in the U.S. are due to medication nonadherence, with total cost estimates ranging between $100 and $300 billion annually. A recent World Health Organization report states that, because the magnitude of medication nonadherence is so alarming, more health benefits worldwide would result from improving adherence to existing treatments, than from developing new medical treatments.” This was backed up by a recent position paper put forward by the Healthcare Compliance Packaging Council (HCPCEurope) and NVC Netherlands Packaging in October, which stated that: “Data collected by major pharmacy chains indicate that roughly 45% of the population need ongoing medication for chronic and/or complex diseases. The figure of patients in the U.S. needing support to stay compliant/adherent/ persistent would therefore be some 150 million, and for Europe in excess of 220 million people of whom 50% give up their treatment within one year while they are supposed to stay on. According to a compliance-monitoring database, every day 10% of those who are engaged with their therapy forget to take their medicine.” So how can we improve existing treatments to ensure greater adherence? There have been a number of launches of ‘adherence-friendly’ pack designs over the past few months which are helping to address these underlying issues, and they aren’t all necessarily ‘high-tech’: Back in the Autumn, AccuDial Pharmaceutical, Inc. launched their AccuDial product with a novel inner and outer label that provides parents and care-givers information to help precisely dose their child based on weight, not age. The novel aspect of this lies in the product’s two-part label that allows consumers to administer a precise dose (in millilitres) of a liquid medication based on their child’s weight. That differs from many children’s medications that are dosed by age or age groups. The precise dosing is made possible due to a patented two-part label that utilises an outer label that “spins”. Primary 12 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

information (Drug Facts) is displayed on the top label, which also features several windows or clear panels. The inner label is printed with weight in 2lb increments and the correct dose in millilitres. The consumer turns the label until its window shows the specific weight of the consumer’s child. Below the specific weight is the precise dose amount. The consumer, using an oral syringe that is supplied with every product, draws the precise amount of medication into the oral dosing syringe, which is calibrated to match every weight/dose on the label. Another simple idea that is providing a great compliance solution is the flavoured glucose stick packs from US Company ‘Meals to Live’, which provides tasty relief to diabetic children. Their new stick packages make it convenient and ‘cool’ for children to prevent low blood sugar. For diabetics, managing blood glucose can be a matter of life or death. High or low readings can be dangerous. Low blood sugar can cause hypoglycemia, with symptoms such as nervousness, sweating, intense hunger, trembling, weakness, palpitations, and speaking difficulty. These symptoms can lead to a coma or seizure if blood sugar isn’t raised. So aiding adherence through ‘funky’ and fun packaging can save lives. A further example of ‘improper dosing’, has previously occurred with drugs such as acetaminophen. Sandra Kweder, M.D., deputy director of the Food and Drug Administration’s Office of New Drugs, said, “Improper dosing is one of the biggest problems in giving acetaminophen to children”. Luckily this particular issue has been tackled recently by Prestige Brands who have voluntarily added a new dosing feature to their Pedia Care and Little Remedies acetaminophen brands. This helps to protect infants and children under the age of two, providing improved accuracy, safety, and innovation. Prestige have further initiatives & product enhancements in the ‘pipeline’, including age-appropriate dosing devices: Infant products that will contain a special dosing syringe and flow restrictors on the bottles; and children’s products, for ages two to 11 years that will also use bottles with flow restrictors and continue to contain dosing cups. Furthermore, innovative slider pack formats such as the ‘BurgoPak’ one continue to grow in popularity, demonstrated by the recent launches in this format of Maalox, Sanofi’s heartburn treatment, and Kalms, G.R. Lanes’ stress & anxiety remedy, providing portability & convenience to aid ‘compliance on the go’. But innovation to aid compliance isn’t restricted to new and novel packaging formats, Why not tackle the ‘raw product’ head-on?, although this does take us into the realm of Science Fiction. In previous posts I have reported on ‘chip in a pill’ technology and in particular the ‘Helius’ product of Proteus Biomedical, a Californian company. Proteus has already signed a partnership with Novartis, the Swiss drug company, to place edible microchips onto its blood pressure drug Diovan, and has launched studies in the US and the UK for its application in diabetes, organ transplants, mental health and tuberculosis. However this has taken a new twist Volume 2 - Issue 1

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recently, as reported in the UK Financial Times on January 15, 2012 where it was stated that “one of Britain’s leading high street pharmacy chains Lloydspharmacy is to offer customers “intelligent medicines” that will allow them to better follow doctors’ orders and monitor their health.” This is the same Proteus technology being trialled by Novartis. In the same way, it will use tablets containing edible microchips that communicate with a disposable monitoring patch attached to a patient’s shoulder, which will receive signals from the swallowed microchip and monitor other bodily functions including sleep patterns, heart rate and posture. It will then transmit the information to mobile phones and computers owned by the patient or their carers. This is a great step forward, but raises the inevitable concerns by some of privacy. For a service which will apparently “cost consumers about £50 a month”, there is also the issue of circumventing the NHS and a further slide to a ‘two-tier’ UK healthcare system. All of these packs are great examples that demonstrate a multilayered holistic approach to compliance, ensuring a far greater chance of adherence success. I’ll highlight more issues and have further thoughts and examples for you in the next issue. Stay tuned!

Chris Penfold is the CEO of Design Cognition Group Ltd, an independent healthcare packaging design consultancy, a Fellow of the Institute of Packaging, 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 years’ packaging advisory experience in the healthcare sector, Chris has a good understanding of packaging design and development (both graphic and 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.

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 13

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An Expert Viewpoint: Building an Adherence Trust Pathway

While electronic monitoring of patients’ medicines adherence is becoming standard practice in clinical trials involving chronic diseases, most patients are left to their own devices outside of the controlled environment. This is why it is important that we do not lose sight of the impact HCPs have when it comes to motivating and supporting patients throughout their treatment. A recent survey 90TEN conducted among 400 hypertensive patients in the UK, showed that 25% of them had forgotten to take their blood pressure tablets on at least one day in the last month, and only 10% of them recalled their healthcare professional (HCP) discussing tips to make taking tablets easier. This is further supported by a Medscape study2 of 257 physicians that showed none of them kept track of their patients’ compliance rates. This implies that the majority of HCPs trust their patients to take their medication in the correct dosage at the right time.

and the new ABC framework, will help begin driving awareness of the importance of adherence from an educational and goal-driven perspective.

Patients Trust HCP’s Recommendations Recent market research conducted among patients with osteoporosis, who subscribed to an adherence programme being managed by 90TEN Healthcare, indicated that most had joined the programme because their HCP recommended it. The respondents in this particular market research also reported 100% adherence to their prescribed medication. The level of trust that is implied by this market research could be maximised to drive patient adherence in more than one way. Most crucial is HCP education. In December 2011, the Ascertaining Barriers for Compliance (ABC) Project published a new framework for the education and training of health professionals in Europe to help manage and support medicines adherence. The report includes a competency framework and diagnostic tool for assessing competency in managing and supporting medicines adherence for HCPs.

Adherence Trust Pathway

Patient Adherence is More Important Now than Ever to Payors We know from the Medscape study that patients’ adherence to medication is not a priority to HCPs managing hypertensive patients. However, a priority shift could be on the horizon following the European Parliament lunch debate in Brussels, during which EPF, CPME, PGEU and EFPIA called for concrete EU-level action for better adherence to therapies.3 Further reports are also expected this year with recommendations to curb medicines wastage and improve patient outcomes in Europe. So we can only hope that these, 14 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Managing and Supporting Patients’ Adherence within a Busy Schedule We all know that the time an HCP can allocate to each patient is very limited. Educating the HCP in motivational interviewing techniques, tooling them up with Morisky-based questionnaires and making their patients’ adherence part of their own performance criteria is idealistic, and only possible if they have sufficient time to spend with the patient, to assess their adherence regularly, and consolidate their motivation into persistence. A patient adherence programme with a solid value proposition that supports the HCPs’ management of their patients’ condition and medication adherence is a valuable asset to any busy HCP and fits well into a ‘trust pathway’.

The Role of Technology to Support the ‘Adherence Trust Pathway’ There are a number of new medication event monitoring systems (MEMS) that can help HCPs track whether patients take their medication. These include ‘smart’ pills and patches, and pill boxes with caps that report when they have been opened. New smartphone apps are available that show patients how to inject, use asthma inhalers, take their blood pressure, Volume 2 - Issue 1

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and change their lifestyle to manage their condition more effectively. But not everyone has a smartphone and, indeed, not everyone is a savvy user of digital technology. As part of a comprehensive patient adherence programme, market research should be conducted to demonstrate how relevant these technologies are to the patients and to highlight any geographical differences before introducing them into an adherence programme. But they should not be used in isolation. The key to building a successful adherence solution is to ensure that the right tools are deployed for the target audience and then built on over time in response to patient demand and through solid evaluation. 90TEN Healthcare certainly welcomes the new ABC framework, which will help set a standard of education across Europe for HCPs. We will use the framework and our knowledge of new technologies to inform our market research among HCPs and patients, so that the patient adherence programmes we are delivering across Europe and Australia offer HCPs a value proposition that not only fits within this framework, but also provides appropriate support and benefits to patients.

Sources 1. Cegedim Strategic Data – Longitudinal Patient Data (UK) DOF/11/0001. 2. Wendy Lipton-Dibner MA; An effective way to increase patient compliance; Medscape: viewarticle/737584 (last accessed 01.02.12) 3. EFPIA – EU Umbrella Organizations Call for a Concrete EUlevel Action for Better Adherence to Therapies. http://www. (last accessed 01.02.12) Carole North is co-founder of 90TEN Healthcare. She has over 10 years’ experience of delivering programmes that increase adherence to treatment by empowering patients to change their health beliefs and behaviours, supporting HCPs to manage those patients, and developing initiatives that help reduce acute hospital admissions. 90TEN Healthcare consistently wins awards for its adherence, concordance, experiential and social marketing campaigns, and is currently delivering patient adherence programmes in 23 countries. Email: Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 15

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The Role of Co-Pay Card Programmes in Medication Adherence As a marketing professional focused on improving medication adherence, it’s exciting to share my views from a US perspective. I’ve had the opportunity to speak, listen and learn from individuals from East to West (France to New Zealand) and delve into successes and best practices. I’ve heard medication adherence referred to as the “next blockbuster brand.” In the US, one of the top reasons why patients don’t fill and refill their medication is prescription cost. This certainly makes sense, right? Not really. In countries where cost is not an issue given socialised medicine, their overall adherence rate is not much better than in the US. In actuality, the most common reasons for non-adherence include, “I don’t feel any difference on the medication”, or “I can’t deal with the side-effects.” We clearly need to delve deeper into a patient’s behaviour in order to create a valueproposition. Co-Pay Cards: Good for Business or Good for Patients? Pharma marketers focus on increasing market share through patient acquisition, and use co-pay cards to encourage patients to fill their brand prescriptions. Moreover, pharma manufacturers are looking for additional strategies that encourage physicians to prescribe their product. There are numerous strategies that get the new therapy established with prescribers, while encouraging patients to refill their medications. These programmes continue to be popular with both prescribers and patients, as evidenced by a Cleveland Research study (counting 86 co-pay programmes in July 2009 versus 295 in January 2011). Patient Acquisition or Patient Retention, That is the Question There has been a gradual shift in manufacturer focus towards patient retention. This may be the result of legislature (e.g., Healthcare Affordability Act) and a move towards outcomes-based contracting and reimbursement. Likewise, it may be that manufacturers are finding it more difficult to acquire new patients. In response, I’ve seen more and more manufacturers create internal teams focused on providing strategic and tactical guidance around medication adherence. In my opinion, these teams help create a holistic view of the patient. I believe manufacturers should keep acquisition in the forefront but not lose sight of the long-term benefits of a retention programme based on patient feedback and behaviour. Create a Patient/Brand Value Proposition This is where I see the true power of co-pay card programmes; a means to engage patients into an ongoing relationship, or patient relationship management (PRM). It’s a two-way street in that manufacturers provide co-pay assistance in exchange for patient opt-in. Sounds simple, right? Not really. There needs to be a value proposition. I believe a patient’s decision to be adherent is part behaviour and part perceived 16 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

value. Patients have their own individual beliefs that affect the way they make decisions about taking their medication. For example, a diabetic patient is motivated to monitor their blood sugar and inject insulin to avoid unpleasant symptoms and long-term effects of high blood sugar. Conversely, a hypertension patient may forget to take the pill or even refill the prescription since they typically don’t feel any difference while on the medication. I’m not suggesting that a simple refill reminder message is sufficient. I believe each patient should have their own personalised support programme based on their feedback. Simply put, adherence solutions won’t work if patients don’t perceive the PRM’s value in exchange for their participation. As a marketer, I like to think I understand what motivates a patient. To be transparent, only a patient themself is the expert in determining the PRM’s value. Although a challenging proposition, manufacturers should try to learn from each patient intervention. This could be the magic pill to truly drive adherence. With over 12 years of experience supporting the pharmaceutical industry, Marc Migliorini has held numerous positions within implementation, client services and account management. Currently the Senior Director of Marketing for OPUS Health, a division of Cegedim Relationship Management, Marc leads all marketing and product innovation efforts focused on medication adherence and patient relationship management solutions. Marc spent the early part of his career with large consulting houses including Accenture and PriceWaterHouse Coopers. Email: Volume 2 - Issue 1

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The HCPC Alliance Awards Innovative Packaging for Better Patient Compliance Over the last years the lament of the pharma industry over the lack of new blockbuster drugs has become increasingly louder, and we hear more and more of companies laying off hundreds or even thousands of their staff. At the same time we hear of governments being forced to cut their budgets, and healthcare is one of the areas of top priority to reduce costs. Whenever the financial aspects of a system come under scrutiny, one should look at its efficiency and its effectiveness, and there is no doubt that the effectiveness of medication leaves something to be desired. However, as former Surgeon General Dr C. Everett Koop said, “Drugs don’t work in patients who don’t take them.”1 Prescription medications are only effective when they are taken. One would assume that the healthcare systems and the pharmaceutical industry would undertake all efforts to make sure that prescribed medicines are taken as intended by the prescribing physician. A white paper released by the Center for Health Transformation2, the 21st Century Intelligent Pharmacy Project discusses “The Importance of Medication Adherence – Saving Lives and Saving Money by Improving Medication Adherence through a Coordinated Approach to Integrated Healthcare medication”, revealing that non-adherence is costly in terms of health, time and money. Fortunately, there are a number of best practices available for exploration and replication. Healthcare consumers and providers can turn towards education, management, technology and packaging as avenues to provide support to patients in an effort to increase adherence. A simple printed calendar on a medication card has been shown to improve adherence to medication by helping patients track their medication regimen and refill on time.3 There are plenty of studies available that show how packaging can improve patients’ adherence patterns, such as the FAME4 study, published in the Journal of the American Medical Association. It showed that blister packaging of blood pressure medication combined with pharmacist counselling improved adherence among elderly patients by nearly 40 per cent compared with regular vials and no counselling. As a result, these patients experienced statistically significant reductions in their systolic blood pressure. Researchers concluded that “provision of blister-packed medications was a key component of the medication adherence program.” But it doesn’t take complex studies to understand that packaging, its design and functionality, the ease of handling, the robustness and other factors play a significant role. Everyone who has struggled to get into a pack, to read the patient information leaflet or to keep track of the medicinal regimen knows that packaging solutions that help the patients in their endeavours to stay adherent are rather the exception than the rule. HCPC, the Healthcare Compliance Packaging Council in the US, and HCPC-Europe have been fighting for decades to raise the awareness of the role packaging plays in patients’ decisionmaking whether or not to be and/or stay adherent/compliant. Both organisations got together and drew up a list of criteria which they esteem to be of significant importance to support 18 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

patients. These elements include the use of colours and icons as well as reminder aids, readability and the ease of use. Accessibility, portability, reclosability and robustness are further points of scrutiny. The most attention however is put on the intuitiveness of use, the presentation of the patient information and the pack’s appeal, while the cost and sustainability, the environmental impact and recyclability complete the list. The highly-regarded Columbus Award5 will be presented to the winners of the HCPC Alliance contest for outstanding adherence enhancing packaging solutions for the second time. The award ceremony will take place within the frame of a conference about Pharma Packaging and Labelling in Rome on March 9th 2012. References 1. Rubin, R. (2007, March 29). Doctors baffled by patients not taking prescriptions, USA Today. Retrieved from www.usatoday. com/news/health/2007/03/28/taking/medicine_N.htm. 2. © 2010 by the Center for Health Transformation 3. Schneider, P., Murphy, J., & Pedersen, C. (2008). Impact of Medication Packaging on Adherence andTreatment Outcomes in Older Ambulatory Patients. Journal of the American Pharmacists Association, 48(1), 58,63. 4. Lee, J., Grace, K., & Taylor, A. (2006). Effect of aPharmacy Care Program on Medication Adherence andPersistence, Blood Pressure and Low-Density Lipoprotein Cholesterol: A Randomized Controlled Trial. JAMA, 296, 2563,2571. 5. Columbus’ derives from Columbus“Egg”, a turn of a phrase that describes a stupefying simple solution for what might appear to be a complex, unsolvable problem. The anecdote about Columbus’ “Egg” suggests that a bright idea remains of little worth unless it’s turned into reality. Tassilo Korab MSc Starting his career as an international Sales Manager, Tassilo Korab has been in the packaging industry for more than 25 years. As a recognised expert in flexible packaging, he holds an MSc in Healthcare Economics, as well as having written several publications on patient compliance, standards and regulations for child resistant packaging and the war against counterfeits.Tassilo Korab is one of the co-founders of HCPC-Europe, the Healthcare Compliance Packaging Council. Email: Volume 2 - Issue 1

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Medication Non-Adherence and the Public Opinion Problem As the co-founder of a medication adherence company, I am a keen follower of all popular press coverage on the topic. Luckily, the adherence problem is finally evolving from “the biggest problem in healthcare you probably didn’t know about” to one with at least some degree of public recognition. With increasing frequency, I come across articles and blogs in the New York Times, the Wall Street Journal, and the like that either focus on or touch upon medication adherence and its role in health and healthcare spending. Although coverage of the topic is not yet on par with coverage of, say, the rise in obesity, the dangers of a sedentary lifestyle, or other similarly significant behavioural health crises, it is now — at least — on the national radar. So far so good. But here is what really puzzles me. After reading each piece, I always examine the slew of reader comments that follow. I’m taking the liberty of paraphrasing now (and perhaps exaggerating a bit here or there), but here is a sampling of the majority of responses I invariably see: 1. P  eople shouldn’t be on all those medications anyways. People take too many pills. 2. P  harmaceutical companies are just pushing pills to make money. Big pharma is evil, etc… 3. T  he side-effects are worse than the disease. We shouldn’t ingest these toxic chemicals. 4. I f drugs weren’t so expensive, we wouldn’t have this problem in the first place. 5. I f people would simply go vegan, go green, and do yoga, we would have no disease or need for pills in the first place. 6. S  ocial inequality (or injustice) is to blame for this problem, and all others. 7. D  octors are all just pill-pushers out to make a quick buck off of us. I could go on, but you get the idea here. The effort to inform the public of the serious consequences of medication non-adherence is met not with a “wow, that’s a real problem” but more often with a snide “Ha! I’ll tell you what the real problem is.” Admittedly, I do recognise the well-described phenomenon of the angry (and anonymous) reader as being more likely to contribute a comment online, skewing the commentary towards the negative. That said, I’m still surprised by the magnitude of the skew in these cases. I try to do my part by contributing a “hey, this really is a problem, and here’s what we should do about it…” comment, but who knows what that accomplishes. Plus, given the confines of a text box, it’s hard to attempt any form of comprehensive reply. So for what it’s worth, here is my point-by-point reply to the grouches: 1. Yes, it’s true that a so-called “polypharmacy” problem exists for some people. It needs to be addressed, of course, but that’s a whole separate issue and — arguably — a much smaller issue than the non-adherence problem. Let’s stay on point. 2. Yes, pharmaceutical companies are large corporate entities that actually make money. They are not non-profits. Pharmaceutical companies also happen to create medications 20 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

that extend lives, improve lives, and even help to create lives, while — at the same time — employing many thousands of Americans. 3. Yes, every drug, every possible treatment, in fact, has possible side-effects, even — in very rare cases — lethal side-effects. However, chronic disease left unchecked has a far worse track record, trust me. As a surgeon, I have played my part in removing limbs, performing brain surgery, and counselling grieving family members as a result of medication nonadherence. It can be ugly, and very depressing. 4. Yes, cost is an issue for some people on expensive medications with no access to assistance programmes. However, cost is not the reason that most people quit taking their medications. Look at European countries with no out-of-pocket medication costs. They have the same adherence problem! Even free medication is not the answer. 5. Yes, adopting a healthier lifestyle is clearly a good thing and should certainly be promoted. That said, a healthy lifestyle will not rid the world of disease. Diseases are caused by three things: bad habits, bad genes, and bad luck, and not necessarily in that order. We can only affect the first one. Good try. 6. Yes, if everyone had equal income, education, and pedigree, that might put a dent in the medication non-adherence problem. But, believe it or not, medication non-adherence cuts across demographics. Even well-educated, well-connected wealthy people have adherence problems. It doesn’t come down so neatly to a cost or an education problem. Costreduction strategies and education only go so far. 7. Yes, most doctors write prescriptions for pharmaceutical products. That’s a part of being a doctor, unless you’re a pathologist and it’s too late. However, when doctors write a prescription they do so with the goal of improving or preventing disease. Even when they’re volunteering (receiving no cash!), or working abroad in a third-world country, you will notice that they still prescribe or administer pharmaceutical products in order to treat chronic disease. Surprised? Okay, enough said, I feel better now. Dr. Katrina Firlik is co-founder and chief medical officer of HealthPrize Technologies, a start-up company with a novel solution to the problem of poor compliance with prescription medications (www.HealthPrize. com). Before founding HealthPrize, Katrina was a neurosurgeon in private practice at Greenwich Hospital in Greenwich, Connecticut, and on the clinical faculty at Yale University School of Medicine. Katrina attended Cornell University, with an undergraduate major in cultural anthropology. She attended medical school at Case Western Reserve University in her hometown of Cleveland, and completed her neurosurgery residency at the University of Pittsburgh, one the largest neurosurgery centers in the country, where she was the first woman accepted to the program. Katrina also completed a specialty fellowship in epilepsy surgery at Yale University. Email: Volume 2 - Issue 1

Regulatory & Market Place

Evolving US Safety Regulations and Risk Management Programmes The US Risk Evaluation and Mitigation Strategies (REMS) requirements for a drug or drug class are continuously evolving. The FDA solicits feedback and collaborates with pharmaceutical companies in an effort to find the right balance between patient risks and benefits. Much of the REMS design has evolved from earlier work on risk management programmes and RiskMAPs. A. Roche/Genentech – Accutane Risk Management Roche and Genentech (recently acquired by Roche), have had extensive experience with the FDA’s changing risk management requirements. Nine Roche medicines have risk programmes with mature drugs, across several therapeutic areas. Two of these products, Accutane® for acne and Cellcept® for transplants, require ETASU, registries, and implementation systems, in addition to medication guides and communication plans, in an effort to avoid birth defects. Roche launched its first voluntary Accutane risk management programme in May 1988, called the Pregnancy Prevention Program (PPP). The PPP was a voluntary programme for both the prescriber and the patient. Its second programme, System to Manage Accutane Related Teratogenicity (SMART) was launched in April 2000, responding to new FDA restrictions. It required mandatory participation by both the prescriber and female patients. In February 2002, Roche’s patents for the drug isotretinoin expired. There are now many other companies selling less expensive, generic versions of the drug. Once generic manufacturers entered the market, risk management was no longer centralised. Since March 2006, the dispensing of isotretinoin in the United States has been controlled by an FDA-mandated website called iPLEDGE. iPLEDGE requires dermatologists to register their patients before prescribing the medication. Pharmacists are then required to check the website or call a call centre to determine if the patient has registered before dispensing the drug. Additionally, doctors and pharmacists must verify written prescriptions in the iPLEDGE system before patients may fill the prescription. And, women must be on a form of birth control.1 The prescription may not be dispensed until both parties have complied. On June 29, 2009, Roche Pharmaceuticals, the original creator and distributor of isotretinoin, officially discontinued both the manufacture and distribution of their Accutane brand in the United States. Generic isotretinoin remains available in the United States through Teva, Ranbaxy and Mylan. Since the iPLEDGE programme pre-dates REMS, which assigns responsibility for the REMS programme to the NDA holder, iPLEDGE was and continues to be sponsored by all isotretinoin manufacturers. It is a mandatory programme for prescribers, all patients (male and female), dispensers and wholesalers. IPLEDGE is a technology-based system, using both a phone and a web interface (www.ipledgeprogram. com) that tracks all registrations. ETASU requires a monthly pregnancy test by a CLIA-certified lab, and results need to be 22 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

entered into the iPLEDGE system before a script can be filled. Components include: • Applications development and hosting • Adverse event management • Data analysis and reporting • Document production and fulfilment • Patient surveys via web and IVR • Call centre management • Pregnancy registry • Education materials design & update • Assessments • Performance-linked  access system requiring pregnancy test results and contraception choices Chart 1 Impact of Isotretinoin Risk Management on Pregnancy Rates

As can be seen in Chart 1, each new risk management programme decreased the frequencies of pregnancy while patients were treated with isotretinoin. With the PPP programme, there were 2.8 to 3.4 pregnancies per 1000 courses of treatment. The SMART programme resulted in 2.1 to 2.3 pregnancies per 1000 courses of treatment. And iPLEDGE produced the least number of pregnancies, 1.3 pregnancies per 1000 female users of the programme.2,3 B. Amgen and Johnson & Johnson (ESA Class REMS) In 2008, the FDA required Amgen to provide an ESA classwide REMS programme for cancer patients. Amgen is currently the sole manufacturer of FDA-approved ESAs, and Johnson & Johnson’s Janssen is a marketing and distribution partner on Procrit. The risks to be managed in this class were based on studies that found ESAs caused tumours to grow faster and resulted in earlier deaths in certain cancer patients. To meet the FDA requirements, Amgen and Johnson & Johnson’s Janssen jointly co-developed a programme called APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs). The programme includes the following components. Physician Tracking • Physician registrations faxed or mailed to a third-party call centre that oversees and monitors compliance • Documentation of HCP’s completion of training on ESA usage Volume 2 - Issue 1

Regulatory & Market Place

Regulatory & Market Place • Discussion of the risks, benefits, and approved usage of ESAs with each patient before they begin treatment • Written acknowledgment from both the doctor and patient that the discussion took place, which are then faxed or mailed to the third-party call centre • Re-enrolment in the programme every three years Hospital Tracking • Dispensing hospitals designate who “assumes the authority and responsibility” to internally coordinate and oversee the institution’s programme (often the pharmacy manager) • Documentation of hospital’s designee’s completion of training module • Compilation of lists of everyone at the hospital who prescribes ESAs to cancer patients • Proof that each one has enrolled in APPRISE • Archive of the written acknowledgments from every cancer patient who receives ESAs Pharmacy Tracking • Validating the prescriber is an approved APPRISE registrant • Receipt of acknowledgement of patient discussion with signatures from HCPs and patients APPRISE Website The APPRISE website,, provides online access to physicians and hospitals to the following literature and forms: Physicians • PPIs • Medication Guides • Dear Healthcare Provider (DHCP) Letters to HCPs • REMS Flashcard (prescriber checklists) • Provider Flashcards (prescriber process flowchart) • HCP Training Module • HCP Enrolment Form •P  atient and Healthcare Professional (HCP) Acknowledgment Form Hospitals • Dear Healthcare Provider (DHCP) Letter to Hospital Directors of Pharmacy/Administrators • Hospital Process Overview • Hospital Designees Training Module • Hospital Enrolment Form Patients • Patient Instructions for Use (for self-administration) C. Amgen Nplate (romiplostim) and GlaxoSmithKline’s ProMacta (eltrombopag) The REMS programme for Nplate and ProMacta, both drugs used to stimulate the production of blood platelets, but manufactured by different companies, have very similar REMS implementations. The FDA may have worked with both manufacturers to achieve this level of harmonisation. Current Trends On-demand printing of medication guides and patient package inserts (PPIs) has become part of standard pharmacy operating procedures with systems such as LDM Group’s 24 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

CarePoints® and Catalina’s PatientLink®. HCP on-demand printing is gaining acceptance with systems such as LDM Group’s ScriptGuide®. Also, systems for reporting adverse events have a longestablished track record, with available solutions such as the FDA’s MedWatch website, the Relsys Argus Safety data management and regulatory reporting system, Oracle AERS, and others. The Missing Link The missing link in REMS ETASU programmes is the feedback loop among the prescriber, the lab (when required), and the pharmacy, which is still paper-based, taxing HCPs and pharmacies with overly burdensome administrative processes. Fortunately, technologies such as iReminder’s MedTriggerSM can automate communications among these stakeholders. Help Patients Comply with Scheduled Tests Patients need to complete lab tests in a timely manner to avoid lapses in their prescription refills. To help patients stay on schedule, MedTrigger schedules automated reminders. Reminders are scheduled to be delivered to patients prior to their anticipated lab dates (e.g. two weeks, one week and two days before) and to confirm that patients will keep their scheduled appointment. When patients report that they will not go, MedTrigger automatically generates alerts to the HCP and the pharmacy. To accommodate different patient lifestyles, MedTrigger contacts the patient according to their preferred method of communication (email, phone, SMS text, iPhone app). If a patient is not reached at one destination, the system then escalates to the patient’s next preferred location. Furthermore, multiple attempts are made at each location until the patient has been reached. This technology ensures that every effort is made to reach the patient. Best Practices and Recommendations We propose a list of best practices and recommendations for implementing REMS. These programmes are still in their infancy and we see opportunities to create effective programmes that will benefit all stakeholders. Facilitate Communications While elements may differ, the foundation of a REMS programme is communications among healthcare providers, pharmacists and patients, as mandated by the FDA. Currently, most of these communications are pre-printed and paperbased. Furthermore, HCPs and pharmacists have to deal with multiple suppliers rather than a single electronic source for generating print materials. Even worse, when documents are revised, their distribution is slow. We recommend automating these communications whenever possible, replacing them with online systems to improve efficiencies and reduce administrative work for all parties. The benefits include: • There will be a single electronic source for generating documents that must be printed • Adequate documents will always be available • Storage and retrieval of documents will be efficient • Compliance levels will increase Volume 2 - Issue 1

Regulatory & Market Place Improve Patient, HCP and Pharmacy Compliance Compliance levels with REMS programmes are low because they interrupt the workflow4 of HCPs and pharmacists and because the implementation of REMS elements is a manual process5. Even the most efficient HCP offices and pharmacies find adherence to these programmes challenging. HCP offices and pharmacies would, therefore, benefit greatly from automation. Examples include: • IVR, email and SMS text reminders to patients to remind them of upcoming laboratory testing and refill dates • Alerts to HCP and pharmacies when patients report that they will not comply with laboratory testing or refill pickups • Distribution and printing of medication guides at the pharmacy and HCP office They also would benefit from online access for: • Pharmacies to determine certification status of HCPs • Prescribers and wholesalers to determine certification status of pharmacies • HCP and pharmacist training and certification • Storage of HCP and patient agreement documents Integrate REMS Programme with Pharmacy Management Systems and HCP Systems The FDA requirement that medication guides be printable from PDF formats has slowed the adoption of electronic medication guides in mainstream pharmacy practice management systems. However, new solutions, such as ondemand printing of medication guides, are being integrated into systems such as QS/1 and SpeedScript using LDM’s CarePoints®. Similar on-demand printing for HCPs office is beginning to emerge as well. Prepare for the Growth of the Generic Drugs Market When new drug applications (NDAs) are filed with the FDA, the REMS accountability remains with the NDA holder and leads coordination among all new sponsors. Therefore, pharmaceutical sponsors facing generic competition down the road should automate for efficiency so that their workload is abbreviated when new drug applications (ANDAs) are approved. We recommend that NDA holders draft a memorandum of understanding (MOU) for all ANDAs and sponsors to sign, which contains: • Rules of engagement • Ownership rights of intellectual properties • Cost-sharing structure • Contracts regarding cost-sharing and third-party call centres • Share of voice and escalation process • The roles and responsibilities of each company’s programme manager •G  overnance (how programme is governed among multiple partners) •E  xit strategy

Following the model established by Roche, we recommend that NDA and ANDA holders share REMS programme development costs. Ongoing maintenance costs should be adjusted based on relative market share. Furthermore, efficiencies are extremely critical when generic sponsors join the REMS programme, since they do not have the same depth of relationships with stakeholders, nor do they have comparable internal infrastructure systems. Automate Reporting Systems Every REMS programme includes an assessment timeline that typically involves a public review of the programme’s impact at 18 months, or after 10,000 patient exposures. Under FDAAA, the agency is required to “prepare…a summary analysis of the adverse drug reaction reports received for the drug, including identification of any new risks not previously identified, potential new risks, or known risks reported in an unusual number.” Improved automation will provide the metrics and improve the reporting necessary to evaluate and continuously advance REMS programmes. Standardise Requirements The key to success for REMS programmes is the standardisation of requirements and uniform methods in design and implementation. And even more importantly, to link REMS to electronic medical records, health plans, and to other adverse event programmes, so that the healthcare system will have the information it needs to effectively treat diverse patient populations. References 1. iPLEDGE Year 1 Review. ac/07/slides/2007-4311s1-04-sponsor-group.pdf Accessed 25 May 2010. 2. Abroms L, Maibach E, Lyon-Daniel K, Feldman SR (2006). What is the best approach to reducing birth defects associated with isotretinoin? PLoS Med. 2006;3:e483. 3. U.S. Food and Drug Administration Briefing document for iPLEDGE year one update. 4. “Use of Medication Guides to Distribute Drug Risk Information to Patients”, Gerald K. McEvoy, Pharm. D., FDA Public Hearing, June 12 and 13, 2007 DrugSafety/UCM173475.pdf Accessed 23 May 2010. 5. Nourjah P, Lee L, Kortepeter C, Avigan M, FDA Office of Drug Safety. National Survey of Pharmacists to Assess Awareness of Drug Risk Communication Tools; 2005. 6. Jean Steckler is the Senior Vice President & Co-Founder of iReminder, LLC, a healthcare technology company. Its products are: Compliance for Life for dosing, appointment reminders and refill reminders; Global e-Trials™ for patient recruitment to and retention in clinical trials; and MedTrigger™ a REMS program that reminds patients to comply with all events required by their risk management plan. Email:

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Regulatory & Market Place

Patient Communities: The Future of Adherence? ‘Pharma companies will succeed or fail based not on how much drug they sell, but on how well their market offerings improve outcomes.’1 Dave Chase As the founder of Microsoft’s health business, which now represents well over half a billion dollars in revenue for the company, Dave Chase knows the pharmaceutical sector inside out. His belief that many pharmaceutical companies need to focus on outcomes to survive is echoed by a range of industry watchers. The Role of Adherence in Successful Outcomes Effective adherence interventions ‘may have a far greater impact on the health of the population than any improvement in specific medical treatments’.2 Adherence is usually crucial to patients achieving good outcomes, yet non-adherence rates for chronic illness regimens and lifestyle changes are estimated to be around 50%.3 Improving adherence is therefore a golden opportunity for pharmaceutical companies to improve patient outcomes. But it’s also an opportunity to improve their own bottom line, as increased adherence leads to a corresponding decrease in the discontinuation and switching behaviour associated with non-adherence.

The reason for the gap between patients’ desire for knowledge and their false perceptions of their regimens may lie in the current realities of healthcare systems. More patients mean ever-increasing pressure on these systems, making it difficult for healthcare professionals to create partnerships with patients. Some observers have gone so far as to describe healthcare systems as broken, with patients being treated ‘like cattle’.7 The result is patients and care-givers who are left alone with ever-more-complex medications, presenting a major barrier to adherence.

Given that 70% of non-adherence is estimated to be intentional4, many well-intentioned programmes that focus solely on the practical barriers to adherence (for example, the complexity and/or inconvenience of regimens, or difficulties associated with medication refill and self-monitoring) are wide of the mark. Intentional non-adherence results from what are known as ‘perceptual’ barriers.5 These relate to a patient’s beliefs about treatment and perception of the regimen. Essentially, intentional non-adherence derives from the balance between patients’ perception of whether or not they actually need to follow a prescribed regimen, and their concerns about following it. In other words, patients who are concerned about side-effects and/or addiction, and who don’t really understand the severity of their disease are far less likely to take the prescribed dose of their medication.

Patient Communities Close the Information Gap Or perhaps not entirely alone. Patients are increasingly connecting with one another in the digital sphere to share information, advice and support about living with chronic illness. We recently conducted an extensive analysis of how patients with a chronic illness are interacting via social media, and found a range of thriving patient communities in the seven countries we surveyed. These communities are enormously popular: WebMD®, a health information provider that employs physicians, healthcare journalists and trained community moderators is ranked 174 in the US and 648 globally.8 This popularity is due in no small part to the communities hosted by the site. These cover a vast array of conditions, and members can start their own communities. Receiving healthcare advice from physicians is a key driver for patients’ engagement with social media, but even communities that don’t offer advice from healthcare professionals are thriving. The stated aim of patient community platform patientslikeme® is to provide ‘a better, more effective way for you to share your real-world health experiences in order to help yourself, other patients like you and organizations that focus on your conditions.’ Founded in 2004, the community already has 133,000 registered users, with thousands of new users joining every month.. The people behind patientslikeme® are committed to improving adherence, and see patient-to-patient interaction as an influential driver of medication adherence. They believe this interaction gives patients the tools they need to understand how their medication is working for them, and to hold each other accountable for following their doctors’ instructions.9 The approach is working, with 44.6% of patients participating on patientslikeme® indicating improved adherence as a result of their participation.10

The Knowledge Vacuum in ‘Broken’ Healthcare Systems The high level of intentional non-adherence – based as it often is on false beliefs – is especially surprising given the findings of a recent global survey of patient groups, which found ‘more, better-informed patients, who are increasingly demanding greater knowledge and a partnership role in healthcare decisions.’6

Complementing Interactions with Medical Teams TuDiabetes® – a community of patients with diabetes – is another good example of how patients are turning to one another for advice and support. Its founder, Manny Hernandez, was inspired to create an online version of an Insulin Pumpers support group he had attended in his hometown of Orlando. According to Manny, the support

Developing Effective Adherence Interventions Pharmaceutical companies who want to take advantage of this opportunity need to develop adherence programmes that address the real causes of non-adherence.

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group taught him ‘more in an hour than I had learned in a year of pumping and what I picked up from those pump veterans, I still use today to accomplish even greater control.’11 The group also allowed him to help others who had only just started using the pump he himself had been using for a year. After seeing the value of being able to share experiences with others through a support group, his vision for TuDiabetes® emerged. In discussing the success of TuDiabetes® – which, with its Spanish language sister site EsTuDiabetes™, now has almost 20,000 members spanning the globe12 – Manny defines the role of patient communities as complementary to, rather than competing with, healthcare professionals. ‘Communities like ours are not out there to substitute but rather to complement the interactions with your medical team. No amount of patient advice can be a substitute for [the advice] you receive from your medical professionals. However, there can be a number of experiences by interacting with other patients that even the most committed medical team will not be able to offer.12 It’s Not What You Say, It’s the Way That You Say It The value of the advice offered in patient communities is that it’s based on personal experience, but other patients could still choose to ignore it, as they might advice offered by their medical team. So why don’t they? Our research covered patient communities across seven countries and – across national borders, and in spite of differing healthcare systems and cultures – we found they all had one thing in common: members overwhelmingly deliver information and advice in a supportive, non-judgemental tone. And the recipients feel confident that the lack of judgement is genuine, because the advisors are encountering/have encountered the same problems. We found a perfect example on a diabetes Facebook community page. A member posted reporting problems around hypoglycaemia, and admitted that he rarely checked bloods before meals. Another member’s response, which stressed the importance of these checks, began with the words: ‘Apologies if this sounds preachy.’ Access to a Wealth of Patient Information As outlined earlier, improving adherence impacts positively on outcomes and on the bottom line of pharmaceutical companies. And patient communities are a proven force in improving adherence. So partnerships with patient communities already offer benefits to such companies.

But there is a further benefit for companies who choose to partner with these communities: access to a wealth of patient information. Patientslikeme® brings patients together to offer and receive support, and share information and data. By facilitating data-sharing, the platform aims to promote better selfmanagement, accelerate research and improve care across all the conditions represented. Those pharmaceutical companies who are involved with the platform gain access to highly valuable patient information, which can assist research and development to accelerate their product pipelines. Nowhere else can pharmaceutical companies access this level of patients’ genuine insights into their illnesses and treatments. Companies can even use the platform to recruit subjects for clinical trials. Companies who have seized this opportunity include Novartis, which has created an open, online community for organ transplant recipients on the platform, and UCB biosciences, which recently invited eligible patientslikeme® members with epilepsy to participate in the Phase III clinical trial of an Anti-Epileptic Drug (AED). Yet pharmaceutical companies are overwhelmingly failing to engage with patient communities and reap the potential benefits they offer. Why is this? Fear of the Unknown The pharmaceutical sector has changed dramatically in recent years, and companies in the sector are only now coming to terms with the changing dynamics of their customer base, and making the transition from drug manufacturers to healthcare solution providers. They’re still trying to find their way through this new landscape, and – put simply – they’re nervous. Traditionally these companies have focused on influencing payers, policy-makers and HCPs, observing regulatory guidelines and steering very clear of any interactions with patients that could be seen as attempts to influence. But the internet – and especially social media – has radically altered the respective roles of HCPs and patients. The results of a recent survey in America, for example, indicated that onefifth of people are using social media to gather information about their healthcare.13 Many patients are embarking on

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 27

Regulatory & Market Place interactions with HCPs with opinions and views of their own, and want to play a role in decisions about their therapy. In this new paradigm, pharmaceutical companies have no choice but to interact with patients. Yet most of these companies still see interactions with patients as enormously challenging, and fraught with potential problems. This attitude – coupled with the resistance to change common to so many large organisations – leads to patient engagements that err so much on the side of caution that they fail to trigger interaction. Stop Worrying and Learn to Love Change It’s surprisingly simple for pharmaceutical companies to create engaging interactions with patients within regulatory guidelines. Most companies are already focusing on patient outcomes. They simply need to migrate this focus into the social media sphere. The companies who have successfully partnered with patient communities have done so safely because they focus purely on patients’ needs – rather than business needs – in the social media sphere. The other barrier to engagement – resistance to change within the organisation – is in part based on fear of failure. Pharmaceutical companies need to realise – and quickly – that although failure is a possibility when engaging with patients via social media, it is almost a certainty in the longer term if no such engagement occurs. Failure can be avoided, however. Through partnerships, companies can leverage the reputation, experience and popularity of existing patient communities. Some companies have chosen to develop their own patient communities and, although results have been mixed, Bayer’s MS-Gateway’s 12,000 members are proof that careful preparation and planning pay when developing patient communities. Bayer successfully applies this methodical approach to other social media initiatives, including its Didget™ blood glucose meter and games console. The Didget™ features an online community with score leader boards, web games and player profile pages. By rewarding children for testing, the game and associated community promote consistent testing in the target group. When helping our clients plan and prepare for engagement with patients through any social media, we recommend the following step-by-step approach: 1. Get the patients’ viewpoint Monitor social media conversations around the disease to understand what really interests the patient and to form a picture of the patient ‘types’ that constitute the community, their various needs and how these needs change throughout the course of the patient journey. Qualitative and quantitative data will help further define these types and their needs, leading to the creation of patient personas. Personas are one of the cornerstones of user experience design. The internet has shifted the marketplace from a mass manufacturing to a mass customisation model, and personas allow user experience designers to avoid a ‘one size fits all’ mentality and accurately identify customers’ needs and desires. The pharmaceutical marketplace is no different, so we create personas of patient types for our clients, and refer 28 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

to these constantly when developing content. The result is content that engages patients by meeting their real needs. 2. Ensure buy-in and assign dedicated resource This step requires – as a minimum – that the company’s executive management understand the value of social media and fully endorse patient engagement via social media. Assemble a core team dedicated to patient engagement. To make organisation-wide ‘buy in’ more likely, team members should represent all business divisions, and to ensure patient engagement is culturally relevant and appropriate they should be drawn from across the organisation globally. 3. Engage where it pays By mapping the patient journey from diagnosis we can help our clients to see the points at which interaction can have the greatest positive impact on outcomes. 4. How to say goodbye We advise our clients to either develop patient social media initiatives as ‘campaigns’ with a clearly defined lifespan from the outset, or to enter initiatives with an ‘exit strategy’ that can allow them to disengage when necessary/appropriate, without leaving communities feeling abandoned. 5. Don’t keep it a secret A social media strategy is pointless unless it is documented, publicised and accessible across the organisation to anyone considering engaging with patients via social media. We help our clients by developing strategy documents and guidelines to which people across their organisations can refer.

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A Leap of Faith Creating meaningful interactions with patient communities requires a leap of faith, but the potential benefits far outweigh any risks, and the risks can be mitigated. Social media is in a constant state of flux, and pharmaceutical companies are arriving late to the party. But these ‘digital immigrants’ have the power to buy the expertise that will help them adapt to the new landscape. By learning from and drawing on the experience of other sectors – such as advertising and marketing – that have been engaging with end-users via social media since its infancy, pharmaceutical companies can reap the benefits of patient interactions and have a real and lasting impact on patient outcomes. A new breed of ‘hybrid’ agencies has grown up in the advertising/marketing sector. These agencies combine the strategic competence and brand awareness of traditional agencies with the technological know-how of digital agencies. They understand that while technology changes constantly, human needs remain the same, and develop solutions that meet human (and patient) needs through technology, rather than using technology as an end in itself. Pharmaceutical companies who leverage the wisdom and experience of these agencies are well placed to reap the benefits of improved patient engagement. 1. T  echCrunch guest post, Saturday, July 23rd, 2011

pharma-3-0-will-drive-shift-from-life-science-to-healthtechinvesting-part-i-of-iii/ 2. Haynes RB (2001). Interventions for helping patients to follow prescriptions for medications. Chochrane Database of Systematic Reviews, 2001, Issue 1. 3. World Health Organization 4. From a joint presentation to PACE 2011 by Atlantis Healthcare and Professor John Weinman, Professor of Psychology as applied to Medicine at the Institute of Psychiatry in the Kings College, London 5. Horne R, Weinman J et al. (2006). Concordance, Adherence and Compliance in Medicine Taking: A conceptual map and research priorities 6. HSCNEWS international, Issue 46, November 2008 7. From a joint presentation to PACE 2011 by Atlantis Healthcare and Professor John Weinman, Professor of Psychology as applied to Medicine at the Institute of Psychiatry in the Kings College London 8. Alexa ranking, July 2011 9. From a presentation by patientslikeme® Chief Marketing Officer and Head of Business Development David S Williams to the 8th Annual Patient Adherence, Communication and Engagement (PACE) Conference 10. Wicks P, Massagli M, Frost J, Brownstein C, Okun S, Vaughan T, Bradley R, Heywood J (2010). Sharing Health Data for Better Outcomes on PatientsLikeMe. J Med Internet Res 2010;12(2):e19 11. TuDiabetes%3F 12. From an interview with Manny Hernandez to mark TuDiabetes® winning Best Patient Community in the Healthcare Engagement Strategy Awards 2010. Source: Creation Healthcare best-patient-community-award/ www.marketingyourhospital. com/2011/03/31/healthcare-marketing-1-in-5-use-socialmedia-to-make-healthcare-decisions/ James Kelway is User Experience director at Hello Group A/S. Based in Copenhagen, this ‘full hybrid agency’ delivers innovative solutions to clients by leveraging digital, creative and strategic competences. Its clients include a world leader in healthcare, and James advises this company on strategies for patient engagement via social media, and has steered a number of patient community websites and social network initiatives. James gained an MA in Design Practice while working on websites including at Reed Elsevier’s b2b division. Reed Elsevier is committed to incorporating social networking technologies and communitydriven website strategies into the business, legal and health sectors. James contributed to its guide to enabling communitydriven design within large, multi-disciplinary teams. Email:

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 29

Behaviour Programmes

Whose Health Litrate? During the first half of 2012, the European Council and Parliament will debate the Commission’s new proposals for updating the directive on information to patients on medicines. The debate will take place against a backdrop of statistics showing that almost half of Europe’s patients are ‘health illiterates’. The most recent data reveals that almost half of Europeans (47%) show limited health literacy, with sharp differences between countries1 The data also shows that one in ten patients takes the wrong dose of medication because they misunderstand the information given to them during consultations with doctors and other healthcare professionals. This has serious potential health consequences, as well as economic implications for health services and the pharmaceutical industry. Advocacy groups say investing in health literacy pays off in the long run as it empowers patients to play a more active role in managing their healthcare. This will become increasingly important as chronic diseases – such as diabetes, hypertension and asthma – rise. More and more patients will be expected to manage their own conditions at home rather than being able to rely on more regular, expensive contacts with healthcare professionals. In October 2011, the European Commission adopted new proposals on information to patients about prescription-only medicines. These proposals are intended to ensure patients have clearer, more reliable information. These new proposals set out for the industry exactly what and how information should be provided, including: • Retaining a strict ban on any DTC advertising, and •Obliging industry to publish certain information that is particularly important for patients, such as the labelling and the package leaflet. The new guidelines also strengthen the rules on pharmacovigilance. These changes include: • The automatic triggering of an examination at EU-level when a member state takes action on a medicine due to serious safety concerns, and • When a company voluntarily withdraws a medicine from the market it must explain the reason. During the first half of 2012, the proposals will be debated once more by both the European Parliament and by the Council of Ministers. The European Health Commissioner, John Dalli, has also announced that the Commission will launch an online ‘Wikipedia’-style tool for patients called Health in Europe: Information and Data Interface (HEIDI). The new ‘HEIDI’ site is intended to be a one-stop shop on health information and data, updated by public health experts, researchers, civil society and national authorities. The measures have been controversial with some because they allow pharmaceutical companies to provide information directly to consumers for the first time. Critics say allowing companies to provide factual information on their own products will open the door to advertising of prescription drugs. Supporters of the plan say quality information in all EU languages should be provided, so that consumers are not taken in by poor-quality online resources. 30 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Whilst these measures are to be applauded for having the correct intentions, they do not take into account that the only people likely to use them are those that are already reasonably “health literate”. Consequently the gap between the literate and illiterate – often caused by social class, age, language, educational standard, disability, etc. – will be widened. To truly help the majority, programmes need to be put into place to effectively communicate with the majority of patients. These programmes then have to be managed by dedicated teams. In an ideal world this would be the patient’s own care team, but in reality this is never going to happen. Compliance and adherence especially are not regarded as priorities by prescribers, and retail pharmacists have become shopkeepers in spite of incentives to encourage them to act differently. It is left to the industry to pick up the pieces and create programmes that will improve the health literacy of patients and, through that, improve adherence. The following list gives some guidance on communicating with patients. Tips on Communicating Effectively 1) Identify the audience Identify the intended users based on epidemiology, demographics, behaviour, culture, and attitude. Be sure the materials and messages reflect the age, social and cultural diversity, language, and literacy skills of the intended users. Consider economic contexts, access to services, and life experiences.2 Beyond demographics, culture, and language, consider the communication capacities of the intended users. Approximately one in six adults has a communication disorder or difference resulting in unique challenges. These individuals will require communication strategies that are tailored to their needs and abilities. 2) Continually evaluate understanding Talk to members of the intended user group before you design your communication intervention to determine what information they need to know and how they will use it. Then, pre-test messages and services to get feedback. Test your messages again, after they have been introduced, to assess effectiveness. Refine content when necessary. Use a posttest to evaluate the effectiveness of the information. 3) Talk to real patients Talk to members of the intended user group before you design your communication intervention to determine what information they need to know and how they will use it. Then, pre-test messages and services to get feedback. Test your messages again, after they have been introduced, to assess effectiveness. Refine content when necessary. Use a post-test to evaluate the effectiveness of the information. 4) Acknowledge cultural differences Cultural factors include race, ethnicity, language, nationality, religion, age, gender, sexual orientation, income level, and occupation. Some examples of attitudes and values that are Volume 2 - Issue 1

Behaviour Programmes interrelated with culture include: • Accepted roles of men and women • Value of traditional medicine versus Western medicine • Favourite and forbidden foods • Manner of dress • Body language, particularly whether touching or proximity is permitted in specific situations Ensure that health information is relevant to the intended users’ social and cultural contexts. 5) Limit the number of messages3 Keep it simple. The number of messages will depend on the information needs of the intended users. As a general guideline, use no more than four main messages. Give the user specific actions and recommendations. Clearly state the actions you want the person to take. Focus on behaviour rather than the underlying medical principles. Use familiar language and an active voice. Avoid long or run-on sentences. Organise similar information into several smaller groups. Many of the same plain language techniques that make the written word understandable also work with verbal messages, such as avoiding jargon and using everyday examples to explain technical or medical terms the first time they are used. 6) Supplement written materials Individual learning styles differ. For many people, visuals are a preferred style, especially for technical information. Film is a great way of putting over messages in a memorable yet simple manner. Many people would rather watch a DVD over and over than try to trawl through written material searching for the information they require. Simple line drawings can help users understand complicated or abstract medical concepts. Make sure to place images in context. When illustrating internal body parts, for example, include the outside of the body. Use visuals that help convey your message. (Don’t just “decorate,” as this will distract users.) Make visuals culturally relevant and use images that are familiar to your audience. Use at least 12-point font. Avoid using all capital letters, italics, and fancy script. Keep line length between 40 and 50 characters. Use headings and bullets to break up text. Be sure to leave plenty of white space around the margins and between sections.4 7) Improve usability of the internet5 Studies show that people cannot find the information they seek on websites about 60 per cent of the time. This percentage may be significantly higher for persons with limited literacy skills. Many of the elements that improve written and oral communication can be applied to online information, including using plain language, large font, white space, and simple graphics. Other elements are specific to the internet. These include: • Enhancing text with video or audio files • Including interactive features and personalised content • Using uniform navigation

• Organising information to minimise searching and scrolling • Giving users the option to navigate from simple to complex information A critical way to make information on the internet more accessible to persons with limited literacy and health literacy skills is to apply user-centred design principles and conduct usability testing. 8) Check for understanding The “teach-back” method is a technique that healthcare providers and consumers can use to enhance communication with each other.6 The person receiving the health information is asked to restate it in their own words — not just repeat it — to ensure that the message is understood and remembered. When understanding is not accurate or complete, the sender repeats the process until the receiver is able to restate the information needed. Critically there appears to be a general view that something needs to be done about health literacy in general. If this can be achieved, public health in general should improve, and the correct use of medication will be a natural consequence. However, knowing who will actually make this happen is a different question. Authorities appear to pay lip-service to it without understanding the real issues. Healthcare professionals can see the need but are constantly being squeezed on time and resource. This leaves the industry to step in and make the most of the opportunity. Good patient adherence to medication benefits all parties. Will the industry rise to the challenge? References 1. European Commission. Regulation (EC) No 726/2004 as regards information to the general public on medicinal products for human use subject to medical prescription and as regards pharmacovigilance. 2. National Cancer Institute. Making Health Communication Programs Work. Washington, DC. 3. Doak C, Doak L, Root J. 1996. Teaching Patients With Low Literacy Skills. 2nd Edition. JB Lippincott Co.: Philadelphia, PA 4. Plain Language Action and Information Network. Available at www. 5. Baur CE. 2005. Using the Internet To Move Beyond the Brochure and Improve Health Literacy. In Understanding Health Literacy. Schwartzberg JG, VanGeest JB, Wang CC, Editors. AMA Press, 141-154. 6. Schillinger D, Piette J, Grumbach K, Wang F, Wilson C, Daher C, Leong-Grotz K, Castro C, Bindman AB. 2003. Closing the loop: Physician communication with diabetic patients who have low health literacy. Archives of Internal Medicine. 163(1): 83-90.

Ian De’Ath is a Partner and Director at Wizzard. Having spent over 10 years within the pharmaceutical industry in the UK and Germany Ian helped to establish Wizzard in 2000. Wizzard specialise in communicating healthcare messages to the public for a range of clients in different industry sectors. Since 2002 they have been running targeted programmes aimed at improving compliance and adherence winning many awards for their effectiveness. Email:

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 31

Clinical Trials The Moral Imperative of Improving Patient Adherence to Pharmacotherapy for Cardiodiabesity, Part I: A Focus on Type 2 Diabetes Mellitus Introduction While the term cardiodiabesity1,2 has not currently gained the same traction as some other terms that have recently entered the biomedical lexicon, it effectively captures three chronic and inter-related diseases of enormous relevance to global public health: diabetes, obesity, and cardiovascular disease. The devastation that these diseases will wreak to global public health and the financial wellbeing of worldwide health systems if not addressed in dramatic fashions is hard to overstate. One aspect of addressing these diseases is improving patient adherence to prescribed pharmacotherapy regimens: it is a global public health moral imperative. Adherence is a component of integrated pharmaceutical medicine3,4, and it is a shared responsibility. Howren5 observed that, despite extensive study over five decades, non-adherence remains a significant problem. This is, in part, a reflection of the “remarkable complexity of patient adherence” and the difficulty in reliably predicting behaviours associated with adherence and non-adherence5. While it is acknowledged that future (and more sophisticated) research is certainly needed, it is the premise of this paper that, given what we do know, a greater concerted and well orchestrated effort is needed among stakeholders in the interim. While patients must play their part, so must everyone else involved in this spectrum, including (but not limited to) government, academics, biopharmaceutical manufacturers, prescribing physicians, dispensing pharmacists, nurses who administer medicines in in-patient settings, hospital administrators and those who run residential healthcare homes, and the news media. In the interests of space, the paper focuses on type 2 diabetes mellitus (T2DM), and provides what it hopes might be provocative suggestions that will lead to pragmatic progress. It should be noted that both authors work in the United States: the points made, however, readily and necessarily translate to other countries. This is the first in a series of papers that will address this issue. Type 2 Diabetes Mellitus Along with obesity and cardiovascular disease, T2DM is a global public health concern of staggering proportions. The International Diabetes Federation (IDF) recently observed that, in 2011, there were 366 million people with diabetes, a figure expected to rise to 552 million by 20306. As one country-specific example, data from the United States 2011 National Diabetes Fact Sheet7 stated that 25.8 million children and adults in the United States—8.3% of the population— have diabetes, with 18.8 million being diagnosed and 7.0 million being undiagnosed. Another 79 million people have prediabetes. (The Fact Sheet used both fasting glucose and A1c levels to derive estimates for undiagnosed diabetes and prediabetes, with these tests being chosen because they are most frequently used in clinical practice.) While these numbers are large, the IDF also observed that “Most people 32 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

with diabetes live in low- and middle-income countries, and these countries will also see the greatest increase over the next 19 years”6; see also 8-10. Diabetes will have a tremendous deleterious influence on the health of individuals and the financial ability of healthcare systems to provide optimum care if not addressed in a concerted manner. It is therefore a moral imperative to do everything we can to provide optimum prevention and therapeutic intervention. There are many factors leading to the T2DM epidemic, which “are embedded in a very complex group of genetic and epigenetic systems interacting within an equally complex societal framework that determines behavior and environmental influences”11. Improving prevention and treatment is therefore a multi-faceted challenge. While an integrated approach is ultimately needed, this paper focuses on one approach within the behavioural domain, i.e., strategies to improve patients’ adherence to pharmacotherapy regimens. Non-adherence to Pharmacotherapy Specific patient encounters help frame the issue of nonadherence. One of the authors (PS) has had the following experiences. These cases are revisited in the paper’s Concluding Comments. Case Study 1 The patient was in her mid-sixties. Having suffered from T2DM for more than 20 years, she had the triad of microvascular complications: proliferative retinopathy, nephropathy with macroalbuminuria, and significant neuropathy with lower extremity ulceration. Despite maximum oral antidiabetic therapy, she refused injections, stating that her mother (deceased with diabetes) was fine until her doctor started insulin therapy, which “killed her.” Case Study 2 The patient was a teenager with type 1 diabetes mellitus (T1DM), which had been diagnosed before puberty. His therapy was twice-a-day mixed insulin. He did not keep blood sugar records. He was admitted in diabetic ketoacidosis (DKA) to the hospital on a regular basis, requiring admission to the intensive care unit and IV insulin. In the past year, he was admitted more than eight times. Howran5 defined the term adherence as one used to describe “the extent to which an individual’s behavior coincides with health-related instructions or recommendations given by a healthcare provider in the context of a specific disease or disorder.” He also emphasised that adherence is as fundamental a component of effective healthcare as the treatment regimen itself. However, despite fifty years of research in this area, non-adherence remains a major problem in both behavioural (e.g., exercise regimens) and pharmacological interventions. While estimates of nonadherence in the literature vary considerably, depending Volume 2 - Issue 1

Clinical Trials upon the length and complexity of the treatment regimen, the population and setting being addressed, and the assessment method used, a meaningful range is from 20% to 80%. While this imprecision may at first seem troubling, any figure in this range is disconcerting, and hence precise knowledge of the ‘true figure’ (however one might wish to define true) is not necessary to realise the enormity of the problem. Financially, medication non-adherence has been estimated to cost upwards of $300 billion annually in avoidable medical spending in the US5:see also 12. Medically, non-adherence has implications for the effectiveness of medical treatment regimens: Not only has non-adherence been linked to treatment failures in specific patients, but it may also directly undermine future treatment efficacy due to its contribution to the development of drug-resistant disease strains. Hence, non-adherence by a group of patients can lessen (or remove) the effectiveness of a drug for other patients who take the prescribed medication in a perfectly adherent manner. Pharmacotherapy for patients with diabetes can often be complicated by the comorbidity relationships between diabetes, obesity, and cardiovascular disease, with more than one condition being treated simultaneously. Often three or even four drugs are needed13. New Medicines Table 1 presents examples of approved antidiabetic drugs, and Table 2 presents examples of new drugs under development as described in the literature. Table 1: Examples of Approved Antidiabetic Drugs

Table 2: Examples of New Antidiabetic Drug Categories

Two comments are pertinent here. While the literature reflects considerable activity in the development of new classes of antidiabetic drugs, recent regulatory mandates concerning additional assessments for cardiovascular safety and the prospective exclusion of unacceptable cardiovascular risk have added a considerable burden, both financially and temporally, in bringing new drugs to market19-21; see also 22. Second, being a new drug per se does not necessarily mean that adherence to it will be better. That said, there may well be some important advantages conferred by certain modifications in both new drugs and ways of enhancing adherence for existing compounds, including decreasing dosing frequency23, administering the drug in a pre-filled pen compared with a vial/syringe24, smaller gauge needles for self-administering drugs, and employment by manufacturers of calendar blister packing for drugs amenable to this25. The Association between Non-adherence and Burden of Treatment Domains prioritised as a burden of treatment (BOT) by patients and providers can serve as a useful foundation for strategies targeting increasing adherence. In a recent study that prospectively defined four domains26, patients prioritised burdens in correctly taking a treatment (the domain termed Administration) and difficulties complying with monitoring (Monitoring). Providers perceived BOT to be associated with difficulty obtaining treatment (Access), and unintended symptoms or consequences of the treatment (Effects). The study examined whether patients with T2DM and their clinicians discuss BOT, including treatment-related effects and self-care demands. Domains contributing to BOT were evaluated based on which party (patient or provider) initiated the BOT discussion. Patients initiated BOT discussions approximately twice as often compared with providers in the domains of Administration and Monitoring, while providers initiated BOT discussions approximately twice as often compared with patients in the domains of Access and Effects. It was also found that although 93.5% of visits contained BOT discussions, BOT was unambiguously addressed only 30% of the time. The authors concluded that the low problem-solving findings represented “missed opportunities for reducing treatment-related disruptions in the lives of patients with diabetes, which may affect adherence and wellbeing”26. The Script Your Future Initiative In May 2011 the US Surgeon General, Dr. Regina M. Benjamin, joined with the National Consumers League to launch the Medication Adherence Awareness Campaign entitled Script Your Future. This is “a new public education campaign to raise awareness among patients about the consequences of not taking medication as directed”27. (Note: This campaign uses a figure of 75% non-adherence to prescription medication.) The campaign focuses on diabetes, respiratory disease, and cardiovascular disease, and includes pilot outreach efforts in six cities: Baltimore, MD; Birmingham, AL.; Cincinnati, OH; Providence, RI; Raleigh, NC; and Sacramento, CA. While the Script Your Future initiative is supported by a coalition of nearly 100 public and private partners and

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 33

Clinical Trials sponsors, including healthcare professional groups, chronic disease groups, health insurance plans, pharmaceutical companies, business organisations, consumer groups, and researchers, the high-profile involvement of the country’s leading physician in launching this campaign at the George Washington University provides powerful evidence of governmental involvement. The campaign was informed by research outlined in a new document entitled “Medication Adherence: Making the Case for Increased Awareness” 28. (The following month Dr Benjamin also participated in the National Prevention Council’s National Prevention Strategy29, the first such strategy of its kind. The Council is comprised of 17 federal agencies, again indicating increasing governmental commitment to health in general.) The Script Your Future website contains information devoted to diabetes30. Pragmatic Strategies to Lower the BOT and Increase Adherence While the literature is replete with discussions of adherence, it is time for nationally and globally concerted action by multiple stakeholders. The Script Your Future initiative just discussed is an excellent example of what can and must be done. In this section, some factors contributing to improved patient adherence have been distilled into actionable strategies for four stakeholders that, in the authors’ opinion, deserve consideration. The Biopharmaceutical Industry Every biopharmaceutical company with an investigational drug entering Phase III trials, as well as all companies with drugs already on the market, should consider appointing a Chief Adherence Officer (CAO), and afford this person the same gravitas given to all other occupants of the company’s “C-wing,” e.g., the CEO, CMO, COO, CIO, and CFO. This individual should ideally be trained in, or at least be willing to rapidly become immersed in, educational and behavioural sciences as well as the biological and pharmaceutical sciences, and to be a proactive leader in interactions with all other patient adherence stakeholders (discussion of educational and behavioural sciences follows shortly). The most important consideration, as always, is the patient, and with expanding patient- and provider-specific BOT domain knowledge, we expect that CAOs would be able to develop many tools and strategies to increase adherence. That said, a more adherent patient population that fills more prescriptions and takes more medication for a chronic condition leads to greater income for a sponsor, leading to a win-win situation. The Media Turner et al.31 commented as follows with regard to the media’s discussions of drug safety issues: “In the era of sensationalist, sound-bite coverage, clinical science sadly falls very low on the list of points to be covered in the allotted 30 seconds of television coverage (it can do somewhat better in print coverage).” Such reporting is exemplified by the tone of coverage given to the publication of a paper in the New England Journal of Medicine purporting to demonstrate a cardiovascular risk associated with the thiazolidinedione rosiglitazone. At a time of considerable disagreement 34 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

between clinical and scientific experts, the news media portrayed the findings in a way that could cause grave anxiety to many patients (see [14] for more detailed discussion). By adopting a much more considered approach, the national nightly television news programmes and national newspapers could set an example for other mass communication services by having their medical correspondents discuss adherence on a regular basis, referring to the Script Your Future campaign each time. For the television media, even 30 seconds on a regular basis would likely be very helpful, as would relatively short but prominently and consistently placed newspaper columns: we leave electronic social media to decide how best to help. Academic Training Institutions Schools of medicine, pharmacy, nursing, and all other schools and colleges training allied health professionals need to redouble attention to the adherence component of their curricula. There are always time pressure issues in intensive Volume 2 - Issue 1

Clinical Trials aspirations for future wellbeing, consistent with prioritisation of the domains of Administration and Monitoring 26. To optimise patient adherence, this model must expand with appropriate prioritisation of all domains which contribute to BOT. First, physicians must become very well trained in the behavioural and educational/communication sciences in order to fulfill the next two tasks. Second, patients must be helped by their physicians to become as knowledgeable as possible about their disease and the full ramifications of non-adherence, which for diabetes include microvascular and macrovascular injuries and their extremely undesirable consequences. Third, patients must be given detailed information and counselling on strategies aimed at facilitating adherence. There is convincing evidence in the literature that medical visit communication is associated with patient outcomes, and that appropriate communication enhances adherencesee 32 . It is therefore particularly noteworthy that the Script Your Future website contains pages devoted to helping healthcare providers enhance their patients’ adherence to their medication regimens. Concluding Comments The outcomes of the two cases presented earlier indicate that much work needs to be done, with the initiation of strategies that are tailored for the patient. In the first case study, it was after lower extremity disease progressed that the patient reluctantly began insulin. This improved glycemic control, but she ultimately required amputation of several toes. In the second case, an insulin pump was started, and although the patient did not take insulin for meals, recurrent DKA ceased, with the change attributed to receiving basal insulin which had been previously “forgotten.” Improving patient medication adherence is a global public health moral imperative and a shared responsibility. All of us involved in integrated pharmaceutical medicine, including the development of medicines, their prescription to patients, and the training and continuing education of all involved healthcare professionals, need to play our part with renewed vigour. training programmes, but creative solutions can be found. In the era of multi-faceted electronic communication, for example, an old-fashioned technique might attract memoryenhancing attention and hence add to the overall approach employed: Devote a one-hour lecture slot shortly before students interact with patients for the first time to asking students to write by hand the following (or a similar) statement over and over: “I must discuss medication adherence with my patients at every possible opportunity.” Physicians The ultimate health team is made up of a patient and a physician (and/or other allied health professionals) in conversation about the patient’s health and wellbeing. The current model is largely one in which the physician is an expert in biology and medicine, consistent with prioritisation of the domains of Access and Effects discussed earlier26, and the patient is an expert in his/her life, which includes issues of health and disease, current wellbeing or otherwise, and

References 1. (accessed 26th December 2011) 2. w Newsletters/200810.pdf (accessed 26th December 2011) 3. Turner JR, 2009, Drug safety, medication safety, patient safety: An overview of recent FDA initiatives and guidances. Regulatory Rapporteur, April issue, 4-8. 4. Turner JR, 2010, New Drug Development: An Introduction to Clinical Trials, 2nd Edition. New York: Springer. 5. Howren MB, 2012, Patient Adherence. In Gellman M, Turner JR (Eds), Encyclopedia of Behavioral Medicine. New York, Springer, in press 6. Whiting DR, Guariguata L, Weil C, Shaw J, 2011, IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Research and Clinical Practice, 94:311-321. 7. American Diabetes Association. Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 35

Clinical Trials diabetes-basics/diabetes-statistics (Accessed 15 December 2011) 8. Guariguata L, Whiting D, Weil C, Unwin N, 2011, The International Diabetes Federation diabetes atlas methodology for estimating global and national prevalence of diabetes in adults. Diabetes Research and Clinical Practice, 94(3):322-332. 9. Misra A, Khurana L, 2011, Obesity-related non-communicable diseases: South Asians vs White Caucasians. International Journal of Obesity, 35:167-187. 10. Anand SS, Tarnopolsky MA, Rashid S, 2011, Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE). PLoS One. 2011;6:e22112. 11. Chen L, Magliano DJ, Zimmet PZ, 2011, The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives. Nature Reviews: Endocrinology, November 8 [Epub ahead of print]. 12. Breitscheidel L, Stamenitis S, Dippel FW, Schöffski O, 2010, Economic impact of compliance to treatment with antidiabetes medication in type 2 diabetes mellitus: A review paper. Journal of Medical Economics, 13:8-15. 13. Grossman E, Messerli FH, 2011, Management of Blood Pressure in Patients with Diabetes. American Journal of Hypertension, 24:863-875. 14. Turner JR, Durham TA, 2009, Integrated Cardiac Safety: Assessment Methodologies for Noncardiac Drugs in Discovery, Development, and Postmarketing Surveillance. Hoboken, NJ: Wiley. 15. Czech MP, Aouadi M, Tesz GJ, 2011, RNAi-based therapeutic strategies for metabolic disease. Nature Reviews: Endocrinology, 7:473-484. 16. Cernea S, Raz I, 2011, Therapy in the early stage: Incretins. Diabetes Care, 34 (Suppl 2):S264-S271. 17. Chao EC, 2011, A paradigm shift in diabetes therapy-Dapagliflozin and other SGLT2 inhibitors. Discovery Medicine, 11:255-263. 18. Whitehead JP, 2011, Diabetes: New conductors for the peroxisome proliferator-activated receptor γ (PPARγ) orchestra. International Journal of Biochemistry and Cell Biology, 43:1071-1074. 19. Caveney E, Turner JR, 2010, Regulatory Landscapes for Future Antidiabetic Drug Development (Part I): FDA Guidance on Assessment of Cardiovascular Risks. Journal for Clinical Studies, January issue, 34-36. 20. Turner JR, Caveney S, 2010, Regulatory Landscapes for Future Antidiabetic Drug Development (Part II): EMA Guidance on Assessment of Cardiovascular Risks, Journal for Clinical Studies, March issue, 38-40. 21. H  irshberg B, Raz I, 2011, Impact of the U.S. Food and Drug Administration cardiovascular assessment requirements on the development of novel antidiabetes drugs. Diabetes Care, 34 (Suppl 2):S101-S106. 22. Caveney E, Caveney BJ, Somaratne R, Turner JR, Gourgiotis L, 2011, Pharmaceutical Interventions for Obesity: A Public Health Perspective. Diabetes, Obesity, and Metabolism, 13:490-497. 23. Saini SD, Schoenfeld P, Kaulback K, Dubinsky MC, 2009, Effect of medication dosing frequency on adherence in chronic diseases. American Journal of Managed Care, 36 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

15(6):e22-33. 24. Buysman E, Conner C, Aagren M, Bouchard J, Liu F, 2011, Adherence and persistence to a regimen of basal insulin in a pre-filled pen compared to vial/syringe in insulin-naive patients with type 2 diabetes. Current Medical Research and Opinion, 27:1709-1717. 25. Zedler BK, Joyce A, Murrelle L, Kakad P, Harpe SE, 2011, A pharmacoepidemiologic analysis of the impact of calendar packaging on adherence to self-administered medications for long-term use. Clinical Therapeutics, 33(5):581-597. 26.Bohlen K, Scoville E, Shippe ND, May CR, Montori, VM, 2012, Overwhelmed Patients: A videographic analysis of how patients with type 2 diabetes and clinicians articulate and address treatment burden during clinical encounters. Diabetes Care, 35:47-49. 27. PressRelease_FINAL.pdf (Accessed 26th December, 2011) 28. Bosworth HB and the National Consumers League, 2011, Medication Adherence: Making the Case for Increased Awareness. cons/m/Script_Your_Future_Briefing_Paper.pdf (Accessed 26th December, 2011) 29. National Prevention Council, 2011, National Prevention Strategy: America’s Plan for Better Health and Wellness. See index.html (Accessed 26th December, 2011) 30. (Accessed 27th December, 2011) 31. Turner JR, Satin LZ, Callahan TS, Litwin JS, 2010, The Science of Cardiac Safety: Centralized Approaches for Phase III Studies Enhance the Quality and Integrity of Collected Data. Applied Clinical Trials, November Supplement, 1-5. 32. Roter D, Hall JA, 2012, Doctor-Patient Communication: Why and How Communication Contributes to the Quality of Medical Care. In Gellman MD, Turner JR (Eds), Encyclopedia of Behavioral Medicine, New York: Springer, in press. J. Rick Turner, PhD, is Senior Scientific Director, Integrated & Translational Cardiovascular Safety, Quintiles. He is a clinical trialist, Editor-in-Chief of the Drug Information Journal, a Senior Fellow at the Center for Medicine in the Public Interest, and a Fellow of the Society for Behavioral Medicine. He is an author of more than 100 peerreviewed papers and articles in professional journals. Email: Paul Strumph, MD, is Vice President, Therapeutic Strategy Lead, Cardiovascular and Metabolic Therapeutic Delivery Unit, Quintiles. He is a Diplomate in Internal Medicine, Pediatrics, Adult Endocrinology, Diabetes and Metabolism, and Pediatric Endocrinology. He is an author of more than a dozen articles in scientific journals and magazines, including Nature, Clinical Pediatrics, the Journal of Clinical Endocrinology and Metabolism, and Diabetes Care. Email:

Volume 1 - Issue 2

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 39

Clinical Trials

The Role of Home Visits in Clinical Trials Participating in a clinical trial can be a significant undertaking for a patient. Depending upon the nature of their condition and the length of the trial, enrolling in a study can mean a large commitment, timewise, emotionally and financially. For all patients time is valuable and maybe even more so for those with degenerative or life-threatening conditions, therefore it can be a difficult decision to set aside some of that time for the benefit of research. In order to run a successful clinical trial, recruiting and retaining the appropriate patient group is the key challenge. Often it can be difficult to identify the patients with the disease area who meet the study inclusion and exclusion criteria. This is particularly noticeable in orphan indications (rare diseases). Once patients have been identified, it is beneficial to all parties to ensure that the study design is such that it is advantageous to the patient, aiding both recruitment and retention. One such way to ensure that a clinical trial has the minimum inconvenience for the participants is to incorporate home visits into the study design. Home visits have been undertaken in clinical trials for many years, however historically only by a very small number of sponsors working with key vendors offering this specific service. Increasingly home visits are being recognised as a fantastic tool to improve patient recruitment1, compliance and retention. The value that home visits provide to assessments of patients is now being recognised2 and consequently the number of clinical trials incorporating home visits into the trial design is dramatically increasing. Recruitment Problems A successful clinical trial is dependent upon identifying and enrolling the appropriate participants who meet the correct inclusion and exclusion criteria. A study will also have a number of patients required to statistically power the results. As such, it is vital that if a patient is identified who meets all the criteria, the trial is designed in such a way to ensure that they are not deterred from entering. The study team should consider in which ways the study design might be offputting3, and look at addressing these issues. Many patients are not enrolled into clinical trials, despite being suitable, for a number of reasons. These reasons can range from not wanting any more medical intervention than that which is necessary to control their condition; not wanting to undergo the procedures required of the protocol; or not wanting to attend the number of hospital visits required. Common problems limiting participants from entering study: • no perceived benefit to the patient • patient is unable/unwilling to travel to site for protocolrelated activities • disease state • distance to the hospital • travel • cost • transportation • inconvenience 38 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Retention and Compliance Problems It can be tempting to think that recruitment is the main battle in achieving suitable patient numbers, however, the retention and compliance of those patients you are able to identify can make a significant impact on the study. It is often the case that the patients can be identified and enrolled but whilst participating in the study they withdraw consent - they “drop out”. In addition, in order to make the data collected from a study of value, the patients must comply with the study requirements. In many cases subject data cannot be used due to lack of compliance. Pledger indicated that non-compliance can have a substantial impact on statistical power and sample size requirements in a clinical trial. He stated that under certain assumptions, the necessary sample sizes needed to be doubled with 30% non-compliance, and tripled with 40% non-compliance4. It is also understood that “satisfied patients are more likely to comply with study requirements and complete their commitment to study participation”5. The consequence of both these situations is that further patients may need to be enrolled, which may require further sites to be identified and approvals granted, all of which have detrimental effects on study timelines and budget. Home Visits as a Solution Using in-home services for patient visits can minimise the disruption of a clinical trial to a patient’s life, thus enhancing its appeal to potential participants. Home visits can provide solutions for the most common drug development challenges in clinical trials; patient recruitment and enrolment; patient compliance; patient retention and patient and investigator satisfaction. Some key questions, when contemplating whether a study requires such measures to aid recruitment and retention include: Is the study on a critical path? Is time of the essence? Are patients limited? If the answer to any of these questions is yes, then it is prudent to consider the options available to ensure that a study is considerate in the demands it places upon the patient. Home visits can provide solutions to the common concerns experienced by patients which may deter them from entering a study: Convenient – By completing the study visit within a patient’s home, it is much more convenient for the patient (and often family member, in paediatric studies), thus minimising the impact of the study on the patient’s day-to-day life. Flexible – Home visits can be scheduled to fit around a patient’s (and parents’, in paediatric studies) daily routine, if allowed by the protocol. Visits can be performed before or after school and/or work, in a variety of locations deemed suitable and safe. More relaxing environment – Having a visit performed at home can minimise the anxiety of travelling into hospital. Patients generally feel safer in their own home. Patients are likely to be far more willing to enter into a clinical trial in Volume 2 - Issue 1

Clinical Trials the first place1 and are far more likely to stay in the study for the duration if treated and assessed at home (or school or workplace where this is appropriate). Working in the patient’s home allows the clinician to provide more of the personal touch, spending more time answering the questions and listening to concerns.

by the research nurse and appointments in the home setting arranged. All subsequent visits were carried out in the home setting including the entire consent process, data collection and biological fluid collection.

“One paediatric patient would happily sit while I gave her intravenous chemotherapy as long as I was dressed as a fairy complete with tiara and wings; she said that I was her “get better fairy” and that the medication was “magic potion”. I was very happy to comply! Home visits result in a happier child and this definitely translates to happier parents and increased compliance.” said Debbie Easlea, Research Nurse at

“During the ‘Building Blocks’ study I visited pregnant teenagers at a venue of their choice. The majority of ladies chose for me to visit them in their own home. I think that, by removing the inconvenience and expense to a participant of asking them to visit at site, that we captured a much higher number of potential participants willing to listen to information about the study. I feel that had we asked them to travel and find the venue at site many would have declined.” explained Jacqui Ford, Research Nurse for ResearchNurses. co.

No travel – For some indications, particularly orphan diseases, patients may have to travel great distances for their routine care visits. To request that they travel this great distance on a more frequent basis for study purposes is likely to be offputting, but the idea that the visit can be performed without the inconvenience and cost of travel may be much more favourable. What Procedures can be Conducted at a Home Visit? The extent of the procedures which are able to be completed in the home environment is often underestimated. Home visits can comprise a number of assessments and procedures, including: • Care coordination • Blood draws for local or central laboratory processing • Centrifugation and sample preparation • Urine and other biological sample collection • Study drug administration • Provision of ancillary supplies • Clinical assessments and questionnaires • Patient training and education • Documentation completion Ideally a study design would incorporate the procedures which require hospital visits into the minimum number of visits, and intersperse these with home visits, where many other assessments can be performed.

Outcome: 1645 subjects were recruited in 12 months.

Case Study 27 Study design: Multiple Phase II/III orphan drug studies, evaluating the safety and efficacy of a product for pulmonary arterial hypertension. Treatment regimen required daily oral dosing with qw, qow, qm safety blood draws. Treatment duration: up to two years. Issues: Compliance with frequent blood draw requirements is problematic. Patients’ disease symptoms included fatigue, shortness of breath, faintness, etc., making site visits difficult since most patients resided some distance from sites. Blood samples required local and central lab testing. Walkin service centres for local lab draws were inconsistent and problematic. Solution: Homecare nursing services to provide remote blood draws for selected visits; local and central lab sample processing. Results: For this study there was a 23% drop-out rate observed; 67% drop-out rate in site-only patients and 3% drop-out rate in homecare patients. Fig 1. % Drop-out rate for multiple Phase II/III orphan drug studies, comparing site only vs homecare 7.

Case Study 1 - “Building Blocks”6 Study design: A randomised controlled trial with a parallel economic modelling study. During the trial, subjects (pregnant teenagers) will either receive regular visits from trained Family Nurses (FN) from early pregnancy (of their first child) until the child is two years old following a prescribed programme, or subjects will receive the usual universal services. Issues: Large number of patients required in a population who are notoriously non-compliant, often remote from the study site, unable to drive, and for whom recruitment in antenatal clinics would be slow to impossible. Solution: Homecare research nursing services were contracted to cover 18 PCT trial sites throughout England. Subjects were initially approached by the midwife team to consent to a home visit by the research nurse. All subjects were contacted 40 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Home Visits in Orphan Indications Orphan diseases or rare diseases affect a small percentage of the population as individual diseases, although currently 3.5 Volume 2 - Issue 1

Clinical Trials In addition, the researchers conducting home visits often find that the opportunity to make such an impact on the individual’s life is an extremely rewarding element of this work. “From a nurse’s point of view it is extremely rewarding to have a patient or their carer turn and say ‘thank you, you have made such a difference to our daily routine’. At a recent visit, the patient’s mother was nearly in tears, she was so grateful.” Sue Mackay, Research Nurse Team Manager, ResearchNurses. co. million people are affected in the UK8. Orphan diseases in the EU are those affecting less than five in 10,000 people, or in the US less than 200,000 people. Due to their rare nature, when suffering with an orphan indication, especially for children, patients may be required to travel a significant distance to their “local” specialist centre. The majority of these diseases are genetic and although symptoms may not appear immediately they are usually present throughout that patient’s life. The reality is harsh, since as many as 30% of children affected by these orphan diseases die before they reach the age of five8. Recruiting and retaining patients with orphan diseases for clinical trials has historically been difficult. Home visiting and the practicalities of community administration are obvious ways to address this issue. They provide an emphatic and beneficial outcome for the sufferer, which is ultimately the gold standard. This in turn can lead to all sorts of other benefits such as reductions in overnight stays in hospital, thereby lowering overheads, and the strong probability of prolonged compliance if the subject does not have to undergo extensive travel to specialist clinics. Patients are initially likely to enter into a clinical trial and more likely to stay in a study for the duration if treated and assessed at home (or school or workplace where this is appropriate). “By allowing experienced research nurses to carry out home visits, the trial data collected is clean and Quality of Life assessments gained are truly accurate. What better way is there to rise to the challenge and trial IMP/medical devices in the environment in which it is anticipated that it will be administered, especially in this challenging and sometimes neglected area of orphan diseases?” Sue Mackay, Research Nurse Team Manager, Conclusion In order to run a successful clinical trial, recruiting and retaining the appropriate patient group is the key challenge. Once patients have been identified, it is beneficial to all parties to ensure that the study design is such that it is advantageous to the patient, aiding recruitment, retention and compliance. The value provided by home visits to assessments of patients is now being recognised and the practicalities understood, and consequently the number of clinical trials incorporating home visits into the trial design is dramatically increasing.

Conducting clinical trials in the home setting can raise new logistical challenges, which need to be considered and resolved. It is therefore essential to consider the experience of the vendor in performing home visits to ensure the best outcome for a clinical trial. References 1. Woodsford P and Cheetham T (2012). Recruiting to clinical trials: hospital or home? Arch Dis Child 2012 97:91. 2. Bracken M, Fleming L, Hall P, Van Stiphout N, Bossley C, Biggart E, Wilson N and Bush A (2009). The importance of nurse-led home visits in the assessment of the children with problematic asthma. Arch Dis Child. 2009 94:780-4. 3. Kibby M (2011). Patient Recruitment Feasibility: Defining clinical trial feasibility and establishing a formula for patient recruitment success. Applied Clinical Trials. Publish date: Jun 1, 2011. 4. Pullar T, Kumar S and Feely M (1989). Compliance in Clinical Trials. Annals of the Rheumatic Diseases 1989; 48: 871 – 875. 5. Bachenheimer J and Brescia B (2007). Reinventing Patient Recruitment: Revolutionary Ideas for Clinical Trial Success. Gower Publishing, 2007 chapter 1. 6. Saunders J, Owen-Jones E and Robling M (2011). Evaluating the family nurse partnership in England: the Building Blocks trial. The Practising Midwife 2011. 7. Innovative in-home clinical service model provides future direction to overcome patient recruitment and retention challenges. Monitor 2009 Nov: 24-26. 8. Rare Disease UK - The National Alliance for people with rare diseases & all who support them. http://www.raredisease. (accessed Jan 2012). Ruth Smith is the Clinical Operations Manager at and sister company Illingworth Research Ltd. As Clinical Operations Manager, Ruth manages a growing team of Project Managers, CRAs and CTAs, in addition to medical writing, regulatory, data management and statistics staff, whilst retaining a senior role in clinical project management. During her career, Ruth has worked as both CRA and Project Manager in all phases of clinical trials, in the UK and Europe, and within numerous therapeutic areas. Clients who have worked with Ruth range from small start-up biotechs to large pharmaceutical companies. Email:

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 41


Chronic Respiratory Diseases and their Challenges Key Facts For chronic respiratory diseases, the incidence has increased dramatically over the past decades. The WHO estimates that hundreds of millions of people suffer every day from chronic respiratory diseases. Their last estimate revealed that approximately 235 million people have asthma, 64 million people have chronic obstructive pulmonary disease (COPD) and millions of others have allergic rhinitis and other chronic respiratory diseases worldwide. This article will focus on asthma and COPD, since they represent the biggest proportion of respiratory diseases. The average asthma prevalence is estimated to be 4.9% for adults (11.8 m) and 8.9% for children (6 m) in the seven major markets: US, Germany, France, Italy, Spain, UK and Japan. The prevalence of moderate to severe COPD in adults aged 40 or older is estimated to be 10.1% (16.4 m). It is believed that the asthma prevalence will stabilise while COPD will grow further with the ageing population. Currently, the treatment of these two diseases is significantly overlapping, and this might change in the future due to different unmet clinical needs.1 Asthma represents a severe burden for healthcare systems, not only in high-income countries but also in low- and middleincome countries. The disease is under-diagnosed and undertreated. Although effective treatment exists, which has shown to dramatically reduce asthma morbidity, a medication can only be helpful if taken properly. Asthma does not kill on the scale of COPD, but can lead to death if medication is not taken at all or is not taken according to the treatment scheme. Having said this, it has to be taken into account that almost 90% of people dying from COPD come from low- to middle-income countries. However, even if the diagnosis might not lead to death in high-income countries, due to available medication and other factors, it is an irreversible disease for which only the symptoms can be alleviated.2 As far as the available medication is concerned, there are a range of acute episode prevention drugs and combination preparations of Beta-2-sympathomimetic agents and cromoglicic acid, antichloinergics, cortisone preparations, theophyllin and leukotriene receptor inhibitors as well as, for acute asthma attacks, quickly acting beta-2sympathomimetic agents for inhalation, and cortisone pills.3 The most commonly used devices include metered dose inhalers (MDI) and dry powder inhalers (DPI). The current gold standard for asthma, which is also highly used in COPD, is the combination of inhaled corticosteroids/long acting bronchodilators (ICS/LABA) which currently have to be taken twice daily. Adherence Challenges in Respiratory Diseases There exist different patterns of non-adherence. For example, a patient may under-use the prescribed prophylactic drug to control or prevent the disease attacks, but may stay adherent to the regular taking of the beta-agonist. Moreover, in times 42 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

of symptom absence it might well be that the patient is not adherent at all or takes the medication very irregularly – if the patient shows symptoms, the adherence rate goes up again. Asthma patients show a poor adherence to therapy: Spector et al. revealed a mean adherence of 47 % in 19 adults following a four-times-daily regimen of an antiinflammatory drug for 12 weeks while Jones, C. et al. revealed mean adherence rates of 67.7% to LTRA, 33.8% to ICS and 40 % to ILBA in 48,751 patients researched. Conservative estimates indicate that almost half of the prescription medications are not taken as prescribed4 (see

graph). For COPD, the adherence seems to be better, as shown by a study of DiMatteo in 2002, with a mean of 68.8% of medical treatment. What are the reasons for this non-adherence for a chronic disease, of which the symptoms can be effectively treated, and which does not entail a difficult or harmful administration of the medication? As in other indications, adherence may be unconsciously not fulfilled, or it can be a reasoned choice by patients. According to the WHO in their essay on “Adherence to long-term therapies�, there are five factors affecting adherence which can be applied and specified for asthma and COPD: Socio-economic factors, health-system related factors, condition-related factors, therapy-related factors and patient-related factors can be taken into account as influencing patient adherence. For the first factor, different cultural and lay beliefs of illness and treatment play a role in non-adherence, as well as poverty, lack of transport and family dysfunction. A crucial factor specifically for asthma and COPD nonadherence involves the correct use of the devices, with healthcare providers lacking knowledge and training in treatment management. Short patient consultations surely add to this important factor for non-adherence. With regard to the conditions of asthma and COPD, an inadequate understanding of the diseases and the lack of severe symptoms in some patient cases plays a role in non-adherence as well. Furthermore, COPD often entails the existence of comorbidities and complex medication schemes which worsen adherence to the individual medications.6 Asthma and COPD Volume 2 - Issue 1

Journal For Patient Compliance Strategies to enhance Health Outcomes 37

Therapeutic medication adherence seems also to be heavily influenced by the therapy-related factor “(perceived) complex treatment”, life-long duration of therapy and frequent dosing of the medication. This is linked to and enforced by the key issue of “healthcare related factor”. Last, but not least, factors that come down to the patient him/herself, such as age and forgetfulness, or misunderstanding of instructions and of the disease, close the loop of the non-adherence problem. Poor adherence to drug therapy and also disease management programs represent the major factors for hospitalisation and emergency assignments.7 Tailored and Joint Patient Programs Fostering Reinforcement are Required It is essential to identify the main factors for non-adherence and, based on them, to develop the right patient-centric program in order to increase and stabilise adherence for respiratory diseases like asthma and COPD. Tailor-made solutions have to be introduced according to indication, product and patient profile. For the case of chronic diseases described and for which the main drivers for non-adherence have been identified, the focus in this article lies on the one hand in overcoming healthcare-related factors such as short consultations, and mainly the lack of knowledge on product use and inhalation technique that is highlighted in George’s findings.8 The problem of a complex treatment regimen (therapy-related factor) and patient-related “misunderstanding” should be tackled by introducing a comprehensive patient program taking into account all the “moments” where the patient gets to interact with their healthcare professional and their medication. These moments happen when the patient for the first time receives the medication at the physician’s office, when he or she visits the pharmacy to get the device, and at each moment when he or she has to administer the drug.

Reinforcement is the formula representing an essential component of all behavioural strategies and shall be used as the main trigger to increase adherence.9 As outlined in the article, it may also be that physicians and pharmacists are not totally aware of the correct use of the devices and the right inhalation technique. Therefore, it is indispensable to first of all train healthcare professionals – physicians, nurses and pharmacists (respectively pharmacy staff) – to completely comprehend the indication. This provides the basis for enabling the patient later to understand his or her disease, the therapy possibilities, and the medication used, side-effects and benefits. This training can be carried out by qualified and trained medical sales representatives, nurses or pharmacists themselves, visiting the physician and the pharmacist. The content of the training should encompass disease-related issues as well as the correct use of the medication and, in the case of the inhalers, the right inhalation technique. The physician can build upon his or her first contact with the patient and explain to them in 44 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

detail the indication, the therapy and the use of the device. Here, misunderstandings can already clearly be revealed and overcome. In order to spare time for the physician, this task could also be carried out by the medical assistants / nursing staff subject to local regulations. The use of the device and the inhalation technique should be trained hands-on by the patients and monitored by the staff at that location. This already identifies problems at a very early stage in the device use and supports patients from the first day on. A starter pack with device, brochures and CDs could further support the patient in the usage of the medication and might foster motivation. As regards the next contact point, the pharmacy, in a comprehensive program, cooperates with the physician. The patient would get their medication at the pharmacy where pharmacist and pharmacy staff are also trained with regard to chronic respiratory diseases and know the medication use and inhalation technique in detail. In order to provide “reinforcement”, the patient would get suitable training and advice so that he or she gets the same messages as from the physician. Moreover, the pharmacists, like the physician / physician staff, will monitor the usage and inhalation technique of the device by the patient in hands-on training, perhaps even accompanied by the use of a checklist to feed back to the physicians / manufacturers. The training for the pharmacist should include product and indication training, as well as more general communication training and education on patients’ needs analysis, in order to consult the patient holistically. With the training of the healthcare professionals, the first important step has been completed in order to achieve the successful education of the patient. Moreover, the issue of short consultation can be bypassed due to the more frequent and detailed care of several stakeholders. There is a much higher chance than before that the patient-related factor of misunderstanding the disease and the therapy can be overcome with the knowledgeable physician and pharmacist via the hands-on training provided. As pointed out beforehand, the next contact is with the daily use of the device. In order to assist the patient in their daily use of the medication (which is necessary in most cases in asthma and COPD), SMS reminders, email reminders, or calls from a medical dialogue / call centre can be applied to address the problem of forgetfulness in patients. SMS reminders and email reminders can be set up relatively easily in an automatic way. Patients can be enrolled into this service and will receive these messages as defined, and these messages can be tailored based on age, demography etc. Medical dialogue / call centres can provide a comprehensive level of support and can answer patients’ questions regarding their therapy, and can also ask the right questions in order to find out if the patient is adherent and uses the device correctly. Specialist medical dialogue centres can be used and trained for the specific products and indications. The manufacturers of course can also set up a dedicated medical dialogue centre themselves. The joint patient management programs outlined are designed to interact with the patient at every stage of their contact with the device. Their success shall be derived from the fact that all stakeholders are involved and motivated, Volume 2 - Issue 1

Therapeutic and are aware of these multiple interventions. This provides the benefit of optimal care to the patient and closing the feedback loop between pharmacist and physician (and even manufacturer).

Such programs result in a “true” win-win situation for every party involved in the program.

Apart from the stakeholders involved in the program, it can also be assumed that the healthcare system would be relieved of a high financial burden as per the reduction in emergency hospitalization, and the treatment of recurring side-effects in asthma and COPD when medication is not taken or not properly taken. Having outlined the importance of the right patient program for respiratory disease in this article and designed a successful program for this situation, there are also other factors to adherence coming in the future which relate to the factor of therapy-related non-adherence issues. In order to improve therapies in chronic respiratory diseases further, once-daily ICS/LABAs are under development and are estimated to have significant advantages in compliance over the current twice-daily treatment. The late stage pipeline

for asthma / COPD is extensive with more than 10 products likely to launch prior to 2018.10 This may well be the next step to drive patient adherence further from a technical point of view. References 1. WHO, Chronic Respiratory Diseases, 2011, in: http://www., 01.02.2012 2. Datamonitor, Pipeline Insight: Asthma / COPD, December 2009, p.4; 3. WHO, “Chronic respiratory diseases” respiratory/about_topic/en/index.html; 01.02.2012; 4. Boehringer Ingelheim medworld, http://www.medworld. de/therapiegebiete/asthma/medikamente/copd.htm, 01.02.2012 5. WHO, Adherence to long-term therapies, 2003, p.48 6, 7,8“George, J et al.: Adherence to disease management programs in patients with COPD, 2007, in: http://www.ncbi., 01.02.2012 9. WHO, Adherence to long-term therapies,2003, p.54 10. Datamonitor, Pipeline Insight: Asthma / COPD, December 2009, p. 1 Kathrin Heinritz graduated from the University of Applied Sciences Furtwangen, Germany, in 2004 with a degree in International Business Administration. She later earned her Masters Degree in International Management at the Northeastern University in Boston, USA, and Università Cattolicà del Sacro Cuore in Piacenza, Italy, in 2009. Between 2005 and 2008, Mrs. Heinritz worked as Project Manager international projects in Service, Sales and Auditing projects for several blue chips in a specialised consulting company serving the automative industry. Here, she was responsilbe for the conceptual set up of the projects as well as their implementation and evaluation worldwide. She joined Celesio Group (Pharmexx’s parent company) in 2009 and worked as Portfolio Manager for Pharmexx between 2009 and 2011 concentrating on harmonization and development of the Pharmexx service portfolio on international level. Pharmexx is a leading international outsourcing partner for companies within the area of Life Science. Since May 2011, she is working as Manager Global Projects being responsible for the roll-out of patient-centric services internationally across Pharmexx which includes the development of service blueprints, customer visits, workshop gearance and the development of tailormade solutions in this area. Mrs. Heinritz also coordinated the processes of a big patient-centric project in Germany. She has also held speeches on Health Management Services on several pharma conferences on international level. Email:

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 45

Modern Technology

Will Advances in Technology Continue to Change the Ever-evolving Patient Adherence Landscape? Further innovative technology is being introduced to help improve patient adherence, but in 2012 will the pharmaceutical industry move with the times or stick with more tradit ional adherence methods? The increasing influence of smart technology to help doctors track patient adherence continues to gather pace as the industry looks ahead. Already in January, one of the UK’s foremost newspapers, the Daily Mail, wrote a piece on how ‘Smart’ pills will soon be available to go on sale in Britain for patients being treated for diabetes and heart conditions. Patches on the skin are also available now that can reveal real-time data on body temperatures and heart rates. Such is the progress being made within smart technology that a smart pill (containing a microchip) can be swallowed by the patient, releasing a signal which is then relayed back via a smartphone. The information tells the patient when the next dose is due, and the doctor has a progress update on tracking medication and dosage levels. The technology to collect additional accurate data faster and to make data more easily available is there. Perhaps what is slightly less advanced, and a challenge for pharmaceutical companies, is how to report and use the data to improve clinical decisions and trigger remote care to patients. The marketplace has an assortment of lifestyle modifications, reminders and feedback mechanisms delivered via iPhone, smartphone applications, websites, SMS and email messaging. Cloud technology allows more accurate real-time data collection. How to use the data is the point which pharmaceutical companies are wrestling with. One of the factors is data privacy and security when transmitting data. Another issue is the lack of consistency in the format of data across prescribing, dispensing, hospital, software and transmitting devices. Having one consistent view of a patient remains a challenge. The authorities will continue to monitor the use of technology very closely; however, it is becoming difficult not to see past the very real benefits of having accurate and upto-date data available to the healthcare provider, who can then use this information to help in forming better treatment decisions. Healthcare provider awareness remains a challenge for drug companies and therefore the development of technology to help doctors improve their treatment decisions is a very significant solution. With the technology landscape evolving every year, feedback to healthcare providers will improve as relevant reports on individual patient health outcomes via portals and smartphone applications become more popular. The pharmaceutical industry is already reaping the benefits on how effective technology can be utilised, especially for sales teams in the field and within marketing operations. Sales reps can access the latest programme outcomes reports through smartphone applications or by the 46 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

popular iPad, helping tailor the doctor conversation based on up-to-date reporting of programme outcomes. Armed with an iPad and a smartphone, sales reps are now better equipped to manage their day, their meetings and their KPIs. Once a system is set-up, the unit costs of each communication are very low. If HCP awareness on diagnosis and treatment are primary challenges which a drug company wants to address, then having a technology solution which improves decision-making on treatment and ultimately, patient outcomes, will be a prime consideration. In terms of what smart technology can do for you as the pharma marketer, smart technology can add value to your brand by raising the profile of your product in the eyes of the prescriber, help build those prescriber relationships, help increase adherence and persistence, and improve sales force effectiveness. Charlie Inglefield is the Business Development Director of Partizan International, based in Partizan’s Geneva office. Charlie recently set up the Swiss operations of Partizan International having worked extensively across Australia and Europe in providing business intelligence and market research to the pharmaceutical and healthcare industries. Email: Volume 2 - Issue 1

Modern Technology

Polymedication Electronic Monitoring System (POEMS) – Introducing a New Technology as Gold Standard for Compliance Measurement Introduction Non-compliance is no longer simply the patient’s inability to follow the physician’s advice. The phenomenon is complex, its occurence is random, it is affected by multiple factors, its predictability is difficult and its public policy implications have been debated over the past decades. Because the knowledge of a patient’s medication-taking behaviour is a prerequisite for any evaluation of drug effectiveness1, accurate measurement of compliance has gained more and more importance over the years. The ideal measurement of compliance was described a long time ago2,3 and should be simultaneously non-invasive, unobtrusive (to avoid the artifact of monitoring a behaviour), objective (to produce reproducible data for each subject), practical and cheap (to maximise use and minimise costs); it should yield immediate results and not be open to manipulation. From Self-report to Electronic Ink Traditional indirect measures like self-report, medication diaries, residual pill counting, pharmacy records, clinician opinion (i.e. which do not demonstrate drug ingestion) satisfy many criteria4. However, they are still limited because of a distant measurement in time and space from the medication-taking event itself. With the emergence of microprocessor technologies in the 1990s, precise timing of medication-taking behaviour with oral solid forms could be generated, and revealed a comprehensive profile of an individual’s drug intake that neither drug serum concentrations nor pill counts would have identified. Although electronic compliance-monitoring devices are considered to provide the most accurate and valuable data5 and are close to a “gold standard” in measuring adherence, they have been mostly used as a research tool owing to their high costs. Some authors suggest using such devices mainly to educate treatment-naïve individuals starting a complex therapy6. We present a new technology of electronic adherence measurement of oral solid forms and describe its advantages compared to the electronic devices currently in use. Medication Event Monitoring System (MEMS®) This technology utilises a computer chip embedded in a specially designed pill-bottle cap to record the time and duration of each opening of the bottle (AARDEX Group Ltd., Sion, Switzerland). MEMS® is today the most sensitive measure of adherence. However, the number of pills taken from the bottle at each opening is unknown and frequently (up to 40% in one study7) patients report to have removed pocket doses from MEMS® drug container or having opened bottles without removing drugs for other reasons8 which may all lead to bias and overestimated adherence7. This also prohibits the use of MEMS® caps in conjunction with other adherence support devices, such as pill boxes, where large quantities of pills are withdrawn at one time. Another drawback of MEMS® is that normally only one medication in the regimen can be monitored, therefore only partial adherence is measured. 48 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Polymedication Electronic Monitoring System (POEMS) This novel technology consists of a polymer film with printed electric circuitries (Confrérie Clinique S.A., Lausanne, Switzerland) and allows the recording of date, time and location of drug removal from a blister-pack. This new technology was first developed to fit commercially available standard blister-packs9, avoiding the transfer of the pills into a dispenser and keeping the primary packaging intact (Fig. 1a). Multidrug blister-packs Figure 1a (left): electronic foil with conductive tracks, battery and antenna fitting a commercially available blister-pack (Confrérie Clinique S.A., Lausanne, CH). Figure 1b (right): Vinalink® blister-pack (Pharmis GmbH, Beinwil a.S., Switzerland) with conductive loops of electronics on its back side (film side) covering the 7x4 cavities prefilled with patient’s individualised medication regimen (front side).

are disposable punch cards like the commercially available easyblist® or Venalink®, and contain the different medications in fixed combination to be taken together (so-called “unit-ofuse”). The multidrug blister-packs are filled manually by many community pharmacists in the UK, in Switzerland, in Germany or in Australia. Applied on those multidrug blister-packs (Fig. 2b) the POEMS film allows for remote compliance monitoring of the whole drug regimen, including co-medications. In a recent randomised controlled trial comparing e-blister-packs and MEMS®-devices, acceptance and internal validity were similar, but the data quality was higher with the e-blister-packs10. Electronic multidrug compliance monitoring has several advantages compared to the MEMS® system. POEMS enables monitoring with one single system in contrast to the filling and handling of multiple MEMS® bottles. Further, the removal of several doses at one time can be recorded as the push-through of any single unit-of-use out of the blisterpack will generate an electronic record. Finally, multidrug monitoring provides data with higher quality10 leading to a more accurate estimate of adherence. Interpretation of Patients’ Records Electronic monitoring of a lead drug with a MEMS® device (Fig. 2) is commonly extrapolated to the entire therapy11, and suspicious records can only be explained by questioning the patient or with the addition of a medication diary12. However, this procedure defeats the purpose of obtaining purely objective data. Electronic monitoring of the entire pharmacotherapy with POEMS (Fig. 3) allows the disclosure of distorted intervals. Thus, it helps to distinguish between probable and improbable drug Volume 2 - Issue 1

Modern Technology

Figure 2: Compliance of a once-daily regimen recorded with a MEMS® device over three weeks. Openings with subsequent drug ingestion are depicted as solid circle; those without drug ingestion are shown as open circles. (8)

Figure 3: Compliance report over seven days of a thrice-daily regimen using a blister-pack with POEMS. Each circle represents the pushing through of the unit-of-use medication contained in one distinct cavity. The six pills prescribed for the morning were filled in two cavities, which had to be opened at the same time. Two pills were filled in the evening cavity and one pill in the bedtime cavity. Triangles depict the breaking of two cavities at the same time.

reactions or side-effects, and to recognise drug-drug interaction and drug resistance, since it allows linking the timing of doses with the efficacy of the drug and with critical health incidents. Some patterns, such as shortening of intake intervals, would remain undiscovered with the monitoring of a lead drug. Conclusion In the search for a gold standard for compliance measurement, electronic films affixed to polymedication blister-packs seem to fulfill all the criteria, i.e. non-invasiveness, unobtrusiveness, objectivity, and user-friendliness. In addition, the transparent compartments on the front side facilitate visual verification of the card content and contribute to the security of drug intake. For the health professionals, monitoring of the entire pharmacotherapy gives insight into all intake patterns and allows linking desirable and undesirable drug responses to a specific drug. In the near future, one can imagine that medication adherence data can be available simultaneously with breaking the electronic wires, so that a failure to take medication could be detected immediately and intervention could be carried out if appropriate. Acknowledgments: The authors thank Dr Willem Kort for his tireless commitment to compliance innovations. Conflicts of Interest: None declared.

References 1. Anonymous. Patient compliance in therapeutic trials. The Lancet 1991; 337(8745):823-824. 2. Pullar T, Feely M. Reporting compliance in clinical trials. The Lancet 1990; 336(8725):1252-1253. 3. Rudd P. In Search of the gold standard for compliance measurement. Arch Intern Med 1979; 139(6):627-628. 4. Laufs U, Rettig-Ewen V, Böhm M. Strategies to improve drug adherence. 2011; 32(3):264-268. 5. Hughes D. When drugs don’t work - Economic assessment of enhancing compliance with interventions supported by electronic monitoring devices. Pharmacoeconomics 2007; 25(8):621-635. 6. Glass T, De Geest S, Hirschel B, et al., Swiss HIV Cohort Study. Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients. Antivir Ther 2008; 13(1):77-85. 7. Bova C, Fennie K, Knafl G, et al. Use of electronic monitoring devices to measure antiretroviral adherence: practical considerations. AIDS 2005; 9(1):103-110. 8. Arnet I, Haefeli WE. Overconsumption detected by electronic drug monitoring requires subtle interpretation. Clin Pharmacol Ther 2000; 67(1):44-47. 9. Jekle C, Krämer I. Validation of an innovative system for compliance measurement: OtCM-blister packages. Poster presented at the 13th congress of the European Association of Hospital Pharmacists, Maastricht, the Neederlands 2008, February 27-29. 10. Jekle C, Krämer I. Randomized controlled trial comparing compliance-monitoring with electonic OtCM(TM)-blister packages and MEMS®. Poster presented at the DPhG-Jahrestagung, Brauschweig, Germany 2010, October 4-7. 11. Knafl G, Bova C, Fennie K, et al. An analysis of electronically monitored adherence to antiretroviral medications. AIDS 2010; 14(4):755-768. 12. Denhaerynck K, Schafer-Keller P, Young J, et al. Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients. BMC 2008; 8(1):5.

Kurt E. Hersberger studied pharmacy in Basel and received his PhD at the Swiss Federal Institute of Technology Zurich in 1992. Besides his part-time work in his own community pharmacy in Basel, he continued his research in the field of Pharmaceutical Care. In 2010 he was appointed professor for pharmacy at the University of Basel. Email: Isabelle Arnet studied pharmacy at the Swiss Federal Institute of Technology Zurich. After 2 years in Baltimore, Maryland, USA she came to Basel, Switzerland and acquired her PhD at the Deparment of Clinical Pharmacology and Toxicology. She then entered the editor company Documed, Basel, Switzerland and was head of the translation services. She joined the University of Basel again in 2008, as a senior scientist at the Pharmaceutical Care Research Group with main topic on compliance. Email:

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 49

Drug Delivery, Drug Packaging, Labelling & Dispensing

Label Solutions Helping to Improve Patient Compliance The development and delivery of healthcare products is a costly business, so it stands to reason that every effort should be made to ensure products are used in the correct manner by the patient or end-user. Besides the initial contact a patient will have with a doctor and the pharmacist, the only further communication they may have is the packaging and labelling. Medical products can often be complex in nature, and detailed directions of what to take, when and what adverse effects might manifest must all be included on one carton or sheet of paper. It is therefore a big responsibility for drug manufacturers to get the job right when conveying vital userinstruction on packaging. Besides this challenge, there is increasing legislative and consumer demand for additional information to be included on the pack. Adding to this concern, there are some very serious statistics that support the need for good quality and additional product guidance: • Each year in the US alone 125,000 people die as a result of non-adherence with a direct cost to the US healthcare system of around $US 100 billion. • 31% of all medicines prescribed don’t even get collected, whilst an estimated 40% of those prescriptions are not taken as directed. What is patient adherence? In essence, this should be a simple matter of the patient taking the medicine for as long as prescribed, and at the right time and dose in accordance with the precise instructions. So how come so many people get it wrong? Sometimes patients feel better and think they don’t need to finish the course. Sometimes patients simply don’t pay enough attention and forget to take the medicine at the right time. Often, the patient has not taken the time to fully understand the directions of use or may be confused about the instructions. In any case, they could be doing so at their own peril. Whilst good user-instruction is important no matter what your product or service is, compared to the consumer market it’s absolutely critical that patient information is well laid out and easy to follow. The presentation and interpretation of the product and user-information has a direct effect on the outcome of the medication prescribed. Unclear labelling or poorly worded user-instructions can have dramatic effects on the patient. Incorrect usage or non-adherence of a drug can cause a side-effect, a health problem, or in the worst case a fatality. Furthermore, if the number of hospitalisations caused by non-compliance were caused by adverse reactions, some drugs would be withdrawn from the market immediately. Clearly there is increasing pressure on the manufacturer to find ways of including additional user-information onto a product, and often this needs to be in a number of different languages. 50 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Compromising Packaging is Not the Answer: Technical jargon and medical terms can often discourage the patient from reading about the drug they have just been given. Furthermore, with so much information that needs to be included, often manufacturers have little option other than to find ways of including it all on the label. Reducing type size can result in the information being unreadable and may discourage the patient from following guidelines, and this may even contravene legislation. As with any product or service, clearly laid out, easy to follow user instruction reduces the need for mid- or post-treatment consultation either with a medical professional or pharmacist, and is more likely to result in a positive outcome. In the case of over-the-counter products this may also increase the likelihood of a referral or even repeat purchase, thus promoting the brand. So What is the Solution to Such a Packaging Challenge? Leaflet labels have played an increasingly important role within the healthcare industry and have become commonplace, especially within the last 10 years, on a variety of healthcare products. Printed in the conventional fashion, leaflet labels combine an ordinary self-adhesive label with a folded leaflet or booklet to provide up to 100 pages of extra user-information within the confines of an ordinary label. Repeat Access to User-Information: Often a patient will develop a side-effect or problem part way through or towards the end of a course of drugs. Loose leaflets in cartons are often regarded as ‘unnecessary packaging’ by the consumer and therefore discarded. Leaflet labels remain securely attached to the product or container ensuring vital user-instruction is readily available throughout the entire course of the drug or medication*. Patient-friendly Information: Packaging designers must consider the different levels of education and literacy amongst patients, and this should be reflected within the user-instruction. Well laid out information that is easy to read, easy to follow and patient-friendly is far more likely to yield a positive patient outcome. Additional space via the leaflet label provides the opportunity for better presentation of often detailed information. This could include text in font sizes that are easy to read, graphs, and bold and justified text. Patient Information for the Young and the Old: Who is the drug intended to be given to? The target audience must be taken into consideration. Increased space for copy allows for easy to follow product information laid out in a manner that is easy to follow by patients young and old. Consider also the fact that the medication may need to be administered to a small child by a parent, grandparent or other guardian. Volume 2 - Issue 1

Drug Delivery, Drug Packaging, Labelling & Dispensing Resealable options can be provided, allowing for easy access into the leaflet label. Peel-off or tear-off portions can also be included on the leaflet label for retention by the patient or on medical records. Patient Information for the Blind and Partially Impaired: Since October 2010 (Article 56(a) of Council Directive 2001/83/EC), Braille has been a mandatory requirement on all EU pharmaceutical packaging, and this includes pharmaceutical products which were launched prior to October 2005. Braille must show the name of the medicine and the appropriate strength, where more than one strength is available. This is familiar territory to carton manufacturers with cartonboard embossing technology being readily available, although it is challenging to print the Braille dots at a height that is legible, and avoid them getting squashed. Until recently, the production of Braille on labelling has posed a challenge to the label printing sector. Thanks to a variety of now proven and tested methods of technology it is possible to supply both overlaminated and non-laminated leaflet labels to the healthcare industry with the inclusion of Braille dots. Globalisation of the Pharmaceutical Market: Those connected to the healthcare industry in any way will have become used to regular news updates of mergers and acquisitions. What does this mean for the packaging suppliers? What this may mean is that medical products may be produced in other parts of the globe. In addition to this, those manufacturers may be looking to merge production of a product and create packs that can be shipped to several different countries. The packaging industry is no stranger to looking at areas of reducing packaging, reducing inventory, minimising production costs and keeping shipping costs down to a minimum. Whilst there are a number of solutions to this issue, care must be taken to ensure the patient information is not compromised. Patient information must remain high on the agenda for pharmaceutical companies considering costreduction exercises. Security and Anti-Counterfeiting Measures: Counterfeit medicines cost the global economy an estimated $1,000bn annually. Additionally, they undermine public trust and integrity in brands and at worst could cause a fatality. Like most forms of labelling and packaging, there are a variety of optional security and anti-counterfeit measures that can be incorporated into the leaflet label. Anti-counterfeit technology may be incorporated into the artwork of both the label and the leaflet either overtly or covertly, allowing for quick and easy detection of genuine products within the supply chain. A simple hologram may be added to the product, or even a simple tamper-evident strip extending the label onto the lid or closure of the container. The Pharmacist Plays an Important Role: On average, the pharmacist will be in discussion with the patient more often than anyone else within the healthcare system. When we think of packaging we often consider individual products or cartons that are handed out in a white

paper bag. But consider the number of products that need to be dispensed from a large container and distributed to individual patients. Each one of them needs to have the correct patient information matched to the correct product and dosage and explained clearly to the patient. Bulk packs may also be labelled in a manner that promotes patient adherence. A large booklet format with 24, 48 or even more pages of user-instruction may be included on bulk packs, each one of them with a perforated area, ensuring this can be torn out and distributed along with the drug at the point of being dispensed. Clinical Trials Labelling: Running a clinical trial is a costly exercise so it’s vital that everything comes together at the right time ensuring the best possible results are yielded. Product information for clinical trials can often be extensive, as clear guidelines need to be set out for both the medical professional and the patient. On average it takes around 12 years and around $800 million to develop an innovative new drug. Adding to this, clinical trials are increasingly carried out by using a cross-section of patients from various geographical locations. Single and double booklet-style leaflet labels in low volumes are often required for such purposes. Whether information needs to be placed onto a standard PET container, a large carton, or even a small syringe or clinical vial, leaflet labels can be adapted to suit. A variety of adhesives ensure the label remains securely attached to the host container. Double perforations may also be cut into the leaflet allowing for complete removal of the information once it reaches the end-user. Clinical trial labelling needs to be fault-free and on time, otherwise the integrity of the trial may be compromised. For example, small colour variations or print faults, which would otherwise be acceptable, may be interpreted by the medical professional and/or the patient as a (false) indication that they are taking the ‘real’ or ‘placebo’ drug. Batch codes, serial data and other variable data needs to be printed and carefully recorded and monitored throughout the process of the trial. This can be achieved either during the production process of the leaflet label, during the labelapplication stage, or even manually during the trial stage. Over-printable materials can be selected for inkjet overcoding plus either during the packing process or even by the pharmacist. Removable portions of the label may even be included for the medical professional to add handwritten notes and attach them to files or records for future reference. Clinical trials labelling also could provide scope for manufacturers to user-test patient information, ensuring commercial products are presented in a manner that is clear to follow and patient-friendly. Medical Device Labelling: Medical devices must be labelled in accordance with stringent rules and regulations. Extensive user-instruction and product information may be included on the leaflet label whilst occupying only the space of the standard self-adhesive label. Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 51

Drug Delivery, Drug Packaging, Labelling & Dispensing

In the example, this tracheotomy kit includes simple userinstruction in diagram layout for soldiers to use whilst in the battlefield (see image attached entitled Portex Battlefield). Product Labelling for Improved Production Conditions: The further benefits of opting for a leaflet label system can be translated into improvements within the production processes. Leaflet labels are supplied on reels, and therefore can be applied directly onto the product or container at high speed using standard label application equipment. A leaflet label may be used in a number of ways to assist with the production processes: 1. Packaging enhancement – the most common reason for switching to a leaflet label is when a manufacturer simply has too much information to include on the label. 2D matrix, pharmaceutical and bar codes, as well as variable data such as batch codes and serial data, can all be added directly onto the leaflet label following strict production guidelines. Scanning equipment ensures correct leaflet to label matching, resulting in fault-free product. 2. Cost-reduction – leaflet labels are frequently used to help a manufacturer reduce production costs. A loose leaflet and carton may be replaced with a single multi-ply label including all the necessary product information, and in several languages too. This can reduce procurement costs, minimise inventory, and also eliminate additional production processes. 3. Over-labelling – frequently leaflet labels are incorporated onto drugs and medicines that have been parallel-imported. This avoids the costly measure of having to remove existing labelling or even re-package vast quantities of product. Leaflet labels can be produced to fit neatly over an existing product label, avoiding consumer confusion and adhering to resale guidelines. Labelling Beyond Legislation: Healthcare labelling is fast becoming more than just functional requirements and fulfilling legal obligations. Labelling and packaging within the pharmaceutical sector is becoming much more a part of the marketing mix. Adding to this, blockbuster drugs coming off-patent will result in increasing competition, especially on those highvalue products. Manufacturers are becoming increasingly aware of approaching pharmaceutical packaging in the same way consumer goods and FMCGs are treated. With scope to dramatically increase the amount of content included within the confines of an ordinary label, brand-owners can be more innovative in the way a product is presented to market. Adding Value to Packaging, Not just Cost: Care must be taken to distinguish between adding features to packaging and labelling ‘because they are aesthetically pleasing’ and adding value to the functionality of the product and the patient outcome. With this in mind it stands to reason that leaflet labels as well as any other forms of on-pack media should be used to the advantage of those concerned in its design, manufacture and usage. Packaging can be an integral part of the treatment. Clear, well laid out packaging and labelling not only improves 52 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

user appeal but it also helps to improve patient outcomes. Final Thoughts: Given the huge cost of developing, testing and launching a new drug, it would be false economy to use cheaper and potentially less effective packaging if it might limit the patient compliance and therefore the effectiveness of the drug. Leaflet labels are a tried and tested method of helping to improve communication with the end-user. In the application of healthcare products, talking to the patient one at a time with well written, well laid out product information that is firmly attached to the product can only prove beneficial. Sources & guidance notes: *Fix-a-Form International commissioned an independent study in conjunction with Magpie Research Services entitled “Pain Killers: A pharmaceutical survey investigating with pack information”. The conclusion was that 24% of all respondents said they would be more inclined to read the instructions if they were attached to the product. Steve Moore is Client Support Executive for Fix-a-Form International Ltd - a UK based leaflet label printing specialist and licensor to a global network of leaflet label printing companies. The Fix-a-Form network comprises 20+ independent label printing companies covering 50+ territories across the globe. Email: Volume 2 - Issue 1

Journal For Patient Compliance Strategies to enhance Health Outcomes 55

Practical Approach

Because Patients Know Best… Everyone in the industry is now striving for Patient-Reported Outcomes. But without patients actually being involved in creating any of these “benefit measures”, are they as useful as they could be? Laura Barnwell looks into emerging platforms to integrate patient feedback and determine what patients believe true therapy payoffs look like. The digital revolution has opened the door, enabling pharma to really get involved in what therapy benefits really look like to their patients and healthcare professionals. In recent years, the quest for payer approval in a rocky economy has been one of the most challenging journeys. Proving patients are realising the benefits of a given therapy has become part of the solution to this challenge. However as formalised qualitative systems, cost-cutting measures take priority, and as a consequence pharma companies are missing the whole point of what it means to be patient-centric. eyeforpharma has teamed up with Simon Davies, CEO of the Teenage Cancer Trust and Chairman of Cancer 52 to find out exactly what “measures” actually make a difference to patients. “We’re going directly to the patients themselves to find out what patient benefits really are, putting them in the driving seat to tell pharma exactly what outcomes really makes a difference to them”. The aim of this exercise is to go beyond the clinical payoffs and traditional metrics and unveil the kinds of benefits patients are really looking for. The perception of success greatly differs from patient to patient, depending on who they are: “a teenage boy suffering from cancer will measure benefit very differently than an elderly woman - and pharma needs to realise the importance of these perspectives and develop ways to respond positively,” says Davies. The challenge lies in finding cost-effective ways to measure and integrate patient feedback and medical outcomes and remain compliant along the way, - and this is where online engagement comes into play. “Online self-management leads to closer collaboration between patients and professionals. The professional has a better understanding of factors impacting the patient,” according to Dr Hans In‘t Veen, Pulmonologist St Franciscus Hospital Rotterdam. As the use of apps, online platforms and social media continues to increase dramatically, patients are becoming increasingly aware of their therapy, disease and others like them. Sites like PatientsLikeMe are gathering vast amounts of volunteered patient data that is helping pharma to understand their patients and evaluate their drugs in a way they have never been able to before. However there is still a big opportunity for pharma to develop platforms like these themselves, but the minefield of compliance and regulation have led to a reluctance to innovate. In’t Veen goes on to point out how tools like this can even go beyond capturing patient feedback: “When patients are at home they have a clear personalised care regime which makes their treatment plan a living record of care,” and undoubtedly tools like this are of extraordinary value to the physician. They are also a way to observe patient adherence behaviours, identify key motivators and improve adherence interventions. In’t Veen has been closely involved in the rollout of a new 54 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

eHealth tool called My Health Monitor at his hospital, tailored for use in the management of COPD and a range of other chronic conditions. “The evaluation of this particular eHealth tool shows that patients with chronic conditions have improved insight and understanding of their disease and increasingly self-manage their disease and treatment.” - Cliff Wyatt, HealthCare21, the creators of My Health Monitor. The rise of the tech-savvy, educated patient has seen the emergence of many adherence interventions via smartphone, apps, web and text messaging services, but long-term adoption of these tools has been relatively low in the pharma space to date. One of the reasons for this could lie in the lack of HCP integration. Achieving patient buy-in to these kinds of tool often lies with nurses, physicians and even pharmacists, so to popularise these tools a real medical benefit needs to be articulated amongst this crucial group, as well as the patient. Annelies Oomen, Nurse Practitioner at a GP in Molenweg, The Netherlands commented that “Using online selfmanagement, professionals can monitor patients more effectively and thus avoid complications, shifting the focus to prevention rather than only intervention. Using an eHealth tool also helps avoid patients waiting too long whilst having treatment.” This message is one that needs to be made central when patient tools and eHealth platforms are in the development stage to ensure maximum patient and HCP buy-in. Both Davies and Dr In’t Veen, along with other thought leaders from Roche, Novartis, Merck and AstraZeneca, plan to challenge the conceptions of the role of the patient in pharma. The emergence of the ePatient is one topic we’re receiving a lot of interest in, and we aim to discover how pharma can incorporate individual patient needs and feedback into meaningful and reactive engagement that aids payer approval, improves therapy and increases adherence. “Success could mean better outcomes for patients, more efficient health economies and more sustainable profits for pharma,” says Davies. “Listen to the voice of the patient,” is a mantra pharma has been championing for the last ten years. However, costcutting, retrenching and R&D pressure has led to this message being somewhat blurred. At this year’s Patient Summit Europe (May 29th-30th London) eyeforpharma is going to be bringing pharma back to this crucial point, discovering not only why but how to capture the voice of the patient in 2012 and beyond. For more information on this year’s Patient Summit Europe visit or contact me directly on the below details. Laura Barnwell is a Global Event Director and is currently working on the European Patient Summit, coming up on the 29th-30th May in London. For more info visit www.eyeforpharma. com/patient or contact her directly at: Email:

Volume 2 - Issue 1

Practical Approach

A Novel Approach to Improving Patient Adherence: Collaboration Across Healthcare Industry Silos It should be so easy. It makes sense for everyone ... the patient takes their medicine properly, they receive the full therapeutic benefit. Their illness or condition is better controlled or even resolved. Professionals feel they’ve done their job well. The patient is better or more capable. Future and expensive medical crises are averted. A plus for all parties. An example --- Stockwell and colleagues at Mt. Sinai Medical Center, showed that a simple series of text messages increased the timely return for second and third HPV vaccinations among girls from 35% to 51.6%.1 In health terms, 16.6% of patients were better protected. In payor terms, the intervention enhanced protection for nearly half of the patients for whom an initial vaccination had been secured. In commercial terms, 47% more vials of vaccine were sold and used. A win for everyone, all at the cost of a few text messages. Bosworth and colleagues at the National Consumers League report that investment in adherence programmes for medications for diabetics yield a seven-to-one return in terms of medical costs for payors.2 Doesn’t it make sense for every product and every positive health behaviour advocacy to have a plan to nudge patients into the desired behaviour? Adherence and compliance are on the lips of many professionals these days. More than a half dozen well-produced meetings are held annually in the US and in Europe, bringing together stakeholders from throughout the field. These meetings, though, have been disappointing to many, consisting often of “infomercial” presentations in the form of podium presentations from vendors who usually tout their solution for one part of the problem. And, like informercials on television, some of these meetings actually sell podium time to vendors to promote their solutions, even though attendees are paying $2,000 and up to sit and listen. Frustrated by the desire for collaboration at these meetings, Inspired Health Strategies brought together a number of likewise frustrated health professionals. This group wanted an opportunity for a meeting using alternative strategies. The group was driven to finally collaborate; to focus on and share best methods and practices in the fields of adherence and compliance. At an initial planning session, held in November 2011, men and women representing pharma, adherence vendors, communications agencies, hospital systems and strategic planners joined together to see how different such a meeting could be. The Powerpoint presentations were limited to a few slides to provoke discussion. They were replaced by flip-charts as idea after idea was floated among the participants. The experience felt good, and it was decided that the workshop format of meeting was much more productive than the conventional meeting format for all concerned. A decision was made to continue the discussion and plan, forming a loosely-structured Patient Adherence Working Group. A plan was laid to expand membership in the group and to conduct a larger meeting for stakeholders in the field to 56 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

take place in New Jersey in the Spring 2012. Our intention is to engage interested stakeholders in conversation and work to see how everyone can understand, and take action on, the goal of having patients take their medication and embark on good-health behaviours for the benefit of all concerned. The Working Group plans to have working meetings open to all willing participants at a minimal cost. The Patient Adherence Working Group concluded: We’re all patients. We’re all customers. At times we’re all non-adherent or non-compliant and we don’t like to be referred to as either. We want to look back at our own experiences to discuss what kind of help, reminders or systems might nudge us to better health behaviours and better health. The Patient Adherence Working Group is an open group. If you would like to join us in our planning, or in our workshops, please contact us at, or follow our progress on Twitter at @PatientAdherence. We are excited at the prospect of finally doing just what we have all only been discussing, truly collaborating across healthcare stakeholders to focus on what is really best for the patient. For the Patient Adherence Working Group: Dyan Bryson, Inspired Health Strategies and Laird Kelly, RSi Communications Founding members of the Patient Adherence Working Group: Stephen Bourke – Celgene Corporation Dyan Bryson – Inspired Health Strategies Celeste Cafiero – Patient Focus, LLC Terri Carlini – One World DMG Sylvester Di Diego – Strategy Dynamix, LLC Frederick Foard – CMI Media Lori Frechtman – Morristown Medical Center, Atlantic Health Meryl Goldman – Inspired Health Strategies Laird Kelly - RSi Communications 1. Kharbanda EO, Stockwell MS, et al. Text message reminders to promote human papillomavirus vaccination; Vaccine, 2011 Mar 21;29(14):2537-41. 2. B  osworth HB, et al. Medication Adherence: Making the Case for Increased Awareness; Whitepaper, National Consumers League 2011. 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: Volume 2 - Issue 1

Practical Approach

Five Principles for Designing Effective Patient Communication Programmes Informative and unbiased patient communication programmes provide a golden opportunity to build better relationships with patients, improve treatment outcomes and strengthen brand reputation among physicians, advocacy groups and other healthcare stakeholders. Patients, who now spend less face-to-face time with their doctors, increasingly seek out independent sources of information about their disease states and potential treatments. For their part, busy physicians want objective sources of information that their patients can easily access and understand. Patient communication programmes often don’t receive as much public attention as some other commercial activities, but their importance and value to global and countrylevel brand teams has grown steadily in recent years. As various players argue the merits – and future – of direct-toconsumer advertising, patient communication programmes have emerged as one of the most reliable ways to provide information to current and potential patients. Direct-toconsumer advertising is not allowed in many markets, and brand teams rely on disease awareness and patient adherence programmes as the only direct means for reaching end users. Cutting Edge Information’s research team pulled the following five principles from the findings of our recent study of patient communication programmes. Participating executives shared their strategies, goals, tools, performance metrics and expectations for the future. The principles are intended to help teams build, assess and improve their patient communications. 1. Tailor Patient-Focused Content to Meet Real-World Needs Designing a patient communication programme that is cohesive, objective and ultimately effective can be a major challenge for teams shepherding new brands, particularly given the sheer number of options now available. Executives discussed roughly twenty major communications tools and channels they must consider, ranging from doctor’s office brochures and call centres, to Web 2.0 activities such as blogs and social networking sites. From country to country, regulations limit the use and availability of different programme components. And although patients are at the forefront of any patient communications campaign, brands may consciously involve doctors in their programmes via tools such as patient resource kits and adherence programmes. Such multi-party channels can create a more collaborative atmosphere among patients, physicians and drug makers. It also reminds doctors that drug companies have patients’ best interests in mind, and that they expend resources to answer questions, promote lifestyle changes and drive adherence to critical therapies. In the past, brands too often used standardised and wideranging communication strategies. Employing such a blanket approach can lead to wasted resources and underwhelming 58 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

brand performance. Today’s health information universe is both too segmented and too crowded for “hit the side of the barn” messaging. It is more effective to build a campaign based on the specific needs and preferences of patients in the therapeutic area. Considering the potential audience’s ‘healthcare behaviour’ can serve as a guide in selecting the best communications methods. For example, a general practitioner’s office can be an effective path for delivering communications to a widespread audience about heart disease. However, an ophthalmologist’s office is better-suited for introducing information regarding glaucoma. Another consideration is the audience’s ability to receive a message. Consider a parent in a pediatric care facility. Though the location for communication is ideal for pediatric care, the audience’s ability to receive that message may be considerably low. With the parents’ attention being diverted to looking after their children, a message must be delivered through a proper medium in order to be effective. In this scenario, brochures will be a good option, as the parent can easily carry the information home with them and read it at a convenient time. Videos, on the other hand, are difficult for the parent to focus on, and the message can be lost amid the surrounding commotion. If brand managers are mindful to keep a message balanced and understand the factors likely to affect its reception, they can select more effective communications tools. 2. Create Clear and Approachable Material Today, nearly every regulated brand has a website explaining the product’s indications and potential side-effects – but it takes much more than a website to ensure patients are directed to the information they can actually understand and use. Brand managers and patient communication teams must weigh which of the tools at their disposal will provide patients with the information they need, when they need it and in a format that fully answers their health questions. Other messaging considerations have to take a back seat to end-user success or the entire campaign will fall flat. For many patients, a brochure or resource kit will be their introduction to a disease or health condition, and it won’t take very much material to overwhelm them with information. While not fitting neatly into some marketing models, this reality seems natural when viewed from the patient’s perspective. If patients are discouraged by the material’s length and complexity, or if the effects of the disease are too emotionally daunting to consider, they are unlikely to read the material. Research on a condition often spans decades, and newer treatments may work in exciting ways that substantially increase their effectiveness or decrease uncomfortable side-effects. Many brand teams are inclined to provide a large amount of sometimes in-depth medical data as quickly as possible to fully inform patients of the ways treatment has advanced. But in order to reach the widest Volume 2 - Issue 1

Practical Approach

possible audience, patient materials should be written at a sixth-grade level; some brand teams find this difficult after being involved in day-to-day tactical work on a product that treats a complex disease state. Specialists working in the field noted that they routinely receive material from drug manufacturers that is too complex and that they get pushback from brand teams when they champion easier-to-understand material. Both brand team executives and consultants agree that simplifying material aimed at patients can be difficult, but that overly complex material is a serious threat to any patient communication programme. 3. Design Materials that Support All Stakeholders Patients are at the forefront of most patient communication programmes, as they should be. Whether the material is aimed at increasing awareness, mitigating side-effects, or improving adherence, its effectiveness will be determined by patients’ ability to understand the material and willingness to implement it in their own care plans. There are plenty of reasons to consider other stakeholders in the patient’s care when designing programmes, however. Even a well-funded patient communication programme will be unsuccessful if the information is not appealing to stakeholders – a group that includes more people than just the patients. With complex or poorly targeted material topping executives’ list of problems for patient communication, brand teams have to enlist the help of physicians, nurses, care-givers, other family members and even regulators to better serve patients. When designing a brochure destined for a doctor’s office, the brand team or consultant must consider that the physician’s opinion of the material will strongly contribute to its effectiveness. If the physician perceives the material as unbiased and thinks that it makes communicating medical information easier, she may use it to help explain an ailment or encourage the patient to take the brochure home. This implicit endorsement from the physician dramatically increases the chance that the patient will read – and trust – the information as well. Some diseases – such as Alzheimer’s disease, Parkinson’s disease, diabetes, and some heart conditions – are more likely to occur in patients who require the assistance of caregivers. These care-givers should be advised on any changes likely to occur in a patient’s life as a result of the disease or the drug used to treat it. They should also be aware of which symptoms may indicate the need for dose modification or emergency care. Brand managers need to carefully consider the entire “ecosystem” of patients’ healthcare experience. For example, in some countries, pharmacists are also considered when crafting materials, as some patients consider pharmacists more approachable than doctors when they have questions about their treatment.

4. Focus on Cultivating Trust Rather than One-Way Delivery of Information In today’s landscape, category-dominating blockbuster drugs are increasingly uncommon, and patients often have multiple options for treatment in many therapeutic areas and want reliable information about those options. As a result, many brand teams are exploring methods of reaching their audiences through alternative channels that are potentially more interactive and flexible. For example, many patients now use the internet as their first source of information about ailments and medical concerns. First-generation patient information websites are somewhat limited to a set interface of established disease information, generalised product recommendations, and detailed information on potential side-effects. This model is giving way to a more interactive use of internet tools. Patients are now using the internet to connect with other patients via chat, blogs, video testimonials, and forums set up by patients to review their experiences with medications. Though online communication presents a danger of misunderstanding and the spread of misinformation, there is also great potential for brands to share information with patients swiftly and accurately. Brands that take a proactive stance in reaching out to patients have the capability to build a relationship with patients as they become a first-stop information resource. If a patient communication programme can help build and support a trusted website, brand teams can be confident that the website will almost always carry a higher level of legitimacy than unregulated blogs and forums. However, brands must be very careful to retain that trust. Any bout with negative publicity is much more devastating in the electronic age as word spreads quickly and remains permanently archived. Regulatory watchdogs also are keeping an ear to the ground on internet communications. Brands must be careful to continue to follow the respective rules of the different countries they serve. Outside the United States and a few other regions, brands stick to disease awareness messages. International brand teams, which have been dealing with the complex web of regulated communication for decades, can provide examples of how to build an effective programme within tight guidelines. If brands seek more interactive communication with their patients and potential consumers, they are likely to deliver information better suited to the specific needs of their audience. In reactionary communications, brands will often find themselves behind the technology of the times and frequently trying to explain their position. In comparison, greater interactivity based on patient preference builds deeper relationships and can establish the groundwork for better health outcomes. Brands treating disease states likely to affect older people will benefit from one-on-one programmes, for example, while Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 59

Practical Approach brands used by younger patients are more likely to see results from internet-based initiatives. Even a brand with a relatively low budget can find ways to implement a programme based on multiple tools and activities. However, the content is ultimately more important than the method of delivery: a concise and accessible brochure will be far more effective than an extensive multimedia website filled with information that is too dense to understand. 5. Choose ROI Measures that Reflect Brand Characteristics Brand teams make decisions about the budget and personnel to invest in specific components of a patient communication programme based on a wide range of factors, including the geographic area being served, revenue projections, the product’s safety profile, and the potential importance of the communication to adherence and correct usage of the product. Survey participants emphasised the need to carefully flesh out the benefits of each tool as well as potential problems for implementation in concrete terms of cost, time, and number of FTEs required. Having made their investment decisions and rolled out a patient communication campaign, brand teams face a major challenge: there is no generic Return-on-Investment model that fits every drug. While patient education teams now understand that one-size-fits-all marketing campaigns no longer meet their patients’ needs, most companies have to adapt to the need for more customized ROI measurement. Of the five most commonly used quantitative ROI measurements – total prescription volume, new prescription volume, returned postcards volume, website traffic and call centre volume – none has earned universal acceptance from patient communications teams as the Gold Standard. The reason is understandable: no single metric can definitively determine the value of so many varied brand strategies. For example, even though a brand team may execute a well-received patient communication campaign, it is often impossible to directly tie a sales increase (or lack thereof) within a specific timeframe to the campaign. Any number of unrelated and often unpredictable factors could have a positive or negative impact, radically altering results: • New trial results • Breaking news from competitor products • Changing field force strategy • Updated pricing and reimbursement strategies • Larger healthcare and market factors Patient communication teams must instead adapt traditional ROI models to better represent their current brand efforts. Many proactive teams have turned to qualitative metrics, which, though often harder to measure, generally better define success. While strategies such as these tend to cost more than calculating numbers (like prescription sales) within a spreadsheet, interviewees assert that qualitative metrics will soon factor as heavily as quantitative measurements for key commercial functions. One profiled brand team regularly contacts all physicians in its programme to gather feedback on the patient brochures left in the doctors’ offices. The team not only uses the responses to refine their materials, and therefore produce more effective collateral, but also 60 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

transmits the data to the company’s executive team. Their leadership understands the clear value of happy physicians. About the Research behind These Principles Cutting Edge Information has conducted benchmarking studies and consulting projects in patient-focused marketing since 2002. For this project, the research team collected quantitative surveys and conducted primary interviews with senior executives associated with brand teams and specialised patient communications groups. Thirty-three companies contributed to this report, including pharmaceutical, biotechnology and medical device companies of varying sizes. Input was also given by consultants specialising in accessibility and distribution of patient communication materials. Study data were compiled from both primary and secondary sources. To gather responses, analysts administered surveys and conducted interviews with executives directly involved in patient communications. The design of the survey and question set was aided by our previous research on patient education, adherence and disease management as well as discussions with industry thought-leaders about current trends in patient communications. The final report examines the structure, goals and tactics of patient communication campaigns. Interviewed executives provided information on their experiences in the United States, European Union, Latin America and Australia. The report details resources and goals of overall patient communication efforts as well as development and performance details for nineteen different patient communications tools. Adam Bianchi is Chief Operating Officer and co-founder of Cutting Edge Information. He has a broad range of expertise helping clients with product development, portfolio planning, brand management, partnerships and mergers, medical affairs management, market access strategy, e-business, customer relationship management, and staffing and structure. Email: Eric Bolesh is a Director of Research with Cutting Edge Information. In addition to co-leading the company’s research division, he has conducted work on earlystage commercialisation, pre-launch marketing, patient communications, business development and licensing, medical affairs, counter-generics strategies, clinical trial operations and research and development strategy. Email:

Volume 2 - Issue 1

Exhibition review

CPHI/ICSE 2011 Review Record Year for UBM’s Pharma Events in Frankfurt (Events Host Over 2,200 Exhibitors, ABC audit Set to Reveal Highest Ever Attendance) November 29, 2011, Amsterdam – Leading event organiser UBM has announced a record breaking year for its flagship portfolio of annual pharmaceutical events including CPhI Worldwide for pharmaceutical ingredients, ICSE for contract and outsourcing services, P-MEC Europe for equipment, machinery and technology and the new InnoPack for innovative packaging solutions. Hosted at Messe Frankfurt, Germany from the 25th to 27th October 2011, the events attracted their highest ever exhibitor levels, with 2,200 global exhibitors on site. Overall attendance, though still subject to ABC audit, is also projected to smash all records set in more than twenty years of the events.* Throughout the three days in Frankfurt, attendees gathered to do business and network across various sectors of the pharmaceutical industry and each individual show experienced growth. P-MEC Europe grew more than 44% over 2010*, and despite exhibitors moving over to the new InnoPack event, ICSE still had a strong showing with over 220 exhibitors*. Notably, the new InnoPack event was met with positive feedback and attendance with over 100 global exhibitors hosting attendees from more than 140 countries. “The scale of the events has grown exceptionally over the years. As an events organiser, it is important to us that the size does not change the opportunity for each visitor to have a unique and personal experience and we invest a large amount of time and money to ensure this,” noted Greg Kerwin, UBM’s Portfolio Director Pharma. He continued, “Despite the financial challenges that still remain globally, to have a year like we just did in Frankfurt means that we are succeeding and that our client base sees the value of these events. As the Pharma industry regroups and rethinks their business plans for the years ahead, we are honoured to continue to be a part of them.” The 2011 pharmaceutical events were centred on a few popular returning features, as well as many new and expanded ones. The Pre-Show Conference on the Monday before the show offered a chance to learn and network before the events got underway. The zoning format also returned, with new additions and once again proved to be a positive feature of the shows by helping to facilitate better time management and ‘more talking, less walking’ while onsite. The expanded zoning format included new zones in CPhI for Generic APIs and Finished Dosage resources, three new zones for New Exhibitors, USA Exhibitors Zone, and Logistics and Supply Chain Zone within ICSE and a Labelling Zone in InnoPack. The CPhI Innovation Awards returned for their eighth year to recognise, celebrate and honour companies

and organisations that are breaking new ground in the pharmaceutical, packaging, contract services and biopharmaceutical sectors. The gold winner of the CPhI Innovation Award was Glycotope for their GlycoExpress platform that optimises the glycosylation of antibodies and other glycosylated biotherapeutics. The Silver medal went to Acuros for their disposable drug delivery device designed to deliver microlitres or millilitres per hour. Finally, bronze was awarded to Johnson Matthey Catalysts for their Colour-Tag-Protein technology that works as a marker for protein expression. The awards were handed out during an exhibitor party that also took a moment to recognize UBM’s shift towards celebrating and supporting sustainability in the events which included awarding Solvias with the Exhibitor Sustainability Award. In addition to the introduction of InnoPack as a standalone event, P-MEC Europe debuted the new LABWorld Pavilion to cater to high technology areas such as instrumental analysis, measuring and testing technologies, materials testing, quality control and laboratory equipment that are separate from the ‘traditional’ large-scale capital machinery, equipment and technology with which P-MEC has become associated. The LABWorld Pavilion was met with positive feedback. Other introductions to the show included Lunchtime Education Series, where high-level presentations from industry leading executives were given in a format that also offered attendees with time to enjoy a lunch while conducting targeted networking. Further new features included expanded social networking platforms and the introduction of virtual events to support attendance from guests that were not able to travel to the events in Frankfurt. CPhI Online has also been developed as a digital meeting spot where visitors can post and find news, information and resources while at the events and throughout the year. UBM’s market leading schedule of annual pharma events include India (30 November - 2 December, 2011, Bombay Exhibition Centre, Mumbai), Japan (21-23 March, 2012, Tokyo Big Sight Exhibition Centre, Japan), CPhI South East Asia (10-12 May, 2012, Jakarta International Expo, Indonesia), ICSE USA(22-23 May, 2012, Pennsylvania Convention Centre, Philadelphia), China (26-28 June, 2012, SNIEC, Shanghai, China), South America (21-23 August, 2012, Transamerica Expo Centre, Brazil) and Worldwide (9-11 October, 2012 at the Feria de Madrid, Spain). Pharma Publications with all their portfolio of publications (Journal for Clinical Studies, IPI – International Pharmaceutical Industry and Journal for Patient Compliance) will be there to support the industry through communications.

Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 61

JPC News

Therapeutic Complexity Linked to Poor Patient Adherence January 12, 2011 — Treatment complexity has a negative effect on patient adherence, a new observational study finds. Niteesh K. Choudhry, MD, PhD, from the Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues reported their study findings online January 10 in the Archives of Internal Medicine. “Because many patients have multiple chronic conditions, therapeutic regimens often involve multiple medications and frequent daily dosing,” the authors note. “Such regimen complexity may undermine effective chronic disease management,” they suggest. The researchers studied data from a national pharmacy benefits manager collected during a 1-year period (June 2006 - May 2007). Treatment complexity was determined over the course of 3 months by analyzing the number of medications, prescribers, pharmacy visits, and visits per fill, which is referred to in the article as “refill consolidation.” Patients included were being treated with either statins or an angiotensin-converting enzyme or renin angiotensin receptor blocker (ACEI/ARB). The statin users were found to fill an average of 11.4 medications at 5 pharmacy visits. Similar results were found for the ACEI/ARB cohort. Adherence to treatment protocols was 68.6% and 66.4%, respectively. In both groups, adherence worsened in those cases with less refill consolidation and a greater number of prescribers and pharmacy visits. An increase in the number of daily doses of medication was also found to have a negative effect on adherence for those patients in the ACEI/ARB group. Source: JCS Staff Writer – Jaypreet Dhillon

between $250 billion and $300 billion per year, or about 13 percent of the nation’s total health care expenditure. This problem led the National Consumers League to launch a major public education campaign in May to raise awareness about the consequences of not taking medication as directed. Source: JCS Staff Writer – Jaypreet Dhillon

New FICO Analytics Predict Likelihood of Patient Adherence to Prescription Medication FICO® Medication Adherence Score enables efficient customization and targeting of programs to help control illness and reduce health care costs. The leading provider of analytics and decision management technology, today announced the launch of the FICO® Medication Adherence Score, which uses predictive analytics to forecast an individual’s likelihood of taking his or her prescription medication as directed. The FICO Medication Adherence Score is a HIPAA-compliant solution that helps improve drug adherence, boosting therapy effectiveness and reducing health care costs. Medical industry estimates show that as many as one-half of the 3.2 billion prescriptions in the U.S. each year aren’t taken as prescribed, and patients consequently run a greater risk of poor health outcomes and more frequent hospitalizations. Nonadherence is cited as the primary cause for 10 percent of hospital admissions and 23 percent of nursing home admissions each year. Some 90,000 deaths per year are attributed to patients’ failure to adhere to anti-hypertensive treatment alone. In financial terms, the industry analyst group IDC Health Insights estimates that poor drug regimen compliance costs the U.S. health care system

Patient adherence anti-hypertensive study The Universities of Bangor and Keele have launched a survey to find out the views of patients who are currently being prescribed antihypertensives. The aim of the research is to explore how a range of factors (economic, psychological, clinical, environmental and social) influence patients’ adherence to antihypertensive treatments. This is part of a wider project of medicines adherence funded by the European Commission ( and being conducted across 17 countries. The study aims to recruit a sample of patients who are currently taking tablets for hypertension through advertisements in Community Pharmacies. Patient participation in the study involves completing an online questionnaire; which includes questions on adherence, and their attitudes, beliefs, and preferences for medicines. The survey will be open until Autumn 2011. The study does NOT require pharmacists to select patients; rather, your participation would require you advertising the survey for patients to self-select. The researchers will provide an A4 poster for you to display and 100 cards for patients to take with them. These provide details of the study and the questionnaire webaddress. Source: ABC Project (Assertaining Barriers to Packaging)

62 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Researchers Develop Strategy To Improve Patient Adherence Physicians can help their patients follow prescribed treatments and achieve healthier results - particularly in chronic disease management - by using a three-pronged strategy developed by a team of researchers from the University of California, Riverside, Texas State University-San Marcos, and La Sierra University in Riverside, Calif. The Information-Motivation-Strategy (IMS) Model - developed after synthesizing findings from more than 100 large-scale studies and meta-analyses conducted between 1948 and 2009 - appears in the peer-reviewed journal Health Psychology Review. Nonadherence costs the U.S. health care system between $290 billion and $300 billion annually and wastes an estimated 275 million medical visits every year, according to study authors Robin DiMatteo of UC Riverside, Kelly Haskard-Zolnierek of Texas State University and Leslie Martin of La Sierra University. HaskardZolnierek and Martin earned their Ph.D.s in psychology at UC Riverside. The World Health Organization estimates that in developed countries half of patients with chronic disease do not adhere to prescribed medication regimens; the number is far worse in developing countries. Source: JCS Staff Writer – Jaypreet Dhillon

Volume 2 - Issue 1

Protomed Tells Future of Pharmacy With Launch of Bemar Barcoding Technology Protomed, creator of Biodose, the world’s only monitored dosage system to accommodate liquid medicines, has launched BeMAR, the world’s first portable, handheld medication tracking device designed to ‘leave no stone unturned’ in the fight against drug error. The system offers pharmacies an opportunity to be among the first to bring barcoding technology to the care home and domiciliary care sector, helping address a glaring source of error innate to the paper-based MAR system – the inaccurate recording of data. Working in tandem with the Biodose medication management system, BeMAR (Biodose electronic MAR) reads barcodes pre-printed onto Biodose pods in the pharmacy. Using the BeMAR wireless scanner which is synched to an iPad, domiciliary carers, nurses or care home staff scan the Biodose pod during their rounds. The iPad then displays an electronic MAR sheet and allows staff to access prescription information from the BNF database, plus patient data taken from medical records at the touch of a button. Staff use BeMAR’s touch screen to log whether medication is taken or refused, at what time and who administered it. The live data is fed instantly into a database, eliminating the potential for error that commonly occurs with handwritten records. The BeMAR data can be accessed immediately by care home managers or pharmacists and used to identify patterns in patient adherence and to monitor staff performance. “To prosper, pharmacy must tap into the NHS’ technology agenda and BeMAR is a vital step in that direction”, commented Norman Niven, Protomed’s CEO. “Put simply, this system will not allow the user to make a mistake – this is a hugely compelling selling point for pharmacies working to maintain and build revenue within the care sector. Even pre-launch, we have had a tremendous response from care homes looking for a pharmacy that can supply this new service, which bodes very well for BeMAR’s success.” The cost of Biodose and BeMAR is shared between the pharmacy and the care home or domiciliary care group. The only such portable handheld device on the market, BeMAR gives pharmacists a powerful USP in offering their care home customers the prospect of improved patient outcomes, reduced round times and less drug wastage. Following the launch of BeMAR, Protomed plans to bring to market Telepak, a telehealth solution which will further expand its range of pro-adherence solutions. Source: Protomed Protomed Grows Graduate Programme By 40 percent Cheshire-based medical innovator, Protomed has announced the extension of its graduate internship programme to cope with the increase in sales for its British-made Biodose products. The company plans to add a further two Manchester University graduates to its burgeoning programme over 2012, with five new recruits already in full-time positions as a result of completing the six-month internships over the past two years.

Patient Adherence and Disease Education Programs Account for 20% of Pharmaceutical Marketing Budgets Benchmarking study results show the budget allocations and ROI for marketing programs A new report from Cutting Edge Information finds that patient adherence and disease education programs consume a combined 20 percent of pharmaceutical brands’ marketing budgets, more than any other single marketing activity, including direct-toconsumer (DTC) advertising. “Pharmaceutical Marketing Strategy: Key ROI Benchmarks to Drive Brand Success” On average, the study found that brands allocate 18 percent of their budgets to DTC advertising. While clearly identifying and isolating return-on-investment on unbranded disease education programs has often proven tough, many drug companies have shifted their focus to patient adherence and education programs to promote long-term disease management and prescription compliance. “Pharmaceutical Marketing Strategy: Key ROI Benchmarks to Drive Brand Success,” analyzed a range of drug marketing campaigns to identify the activities that have the strongest return on investment and outline why they are so effective. In the case of adherence and education programs, companies attempt to grow market share by informing patients of a disease’s long-term effects in the hopes that they will seek treatment. “Educational materials are a relatively inexpensive way for companies to inform patients already in a physician’s waiting room,” said Jeremy Spivey, senior research analyst at Cutting Edge Information and the study’s lead author. “They are excellent for improving a company’s reputation with healthcare providers, as nurses and physicians appreciate high-quality unbranded educational material they can provide to their patients upon diagnosis.” By emphasizing the importance of taking a treatment as prescribed, patient education materials support better adherence, which results in higher prescription renewal rates. The value of these pamphlets – and their relatively low development costs – helps explain why 84% of pharmaceutical companies are involved in patient education activities. “Pharmaceutical Marketing Strategy: Key ROI Benchmarks to Drive Brand Success” examines the brand impact and return on investment for various pharmaceutical marketing budget strategies. The study is designed to help companies meet goals identified by benchmarking partners, including: • Boost brand value and the corporate bottom line with benchmarks for specific marketing activities. • Determine the effectiveness of both traditional marketing activities and newer tools, including Internet-based channels. • Track hard-to-find pharma marketing ROI data for various activities. • Discover where marketing executives can best make future investments. Source: Cutting Edge Information Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 63


✓ PATIENT COMPLIANCE Strategies to enhance Adherence and Health Outcomes

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64 Journal For Patient Compliance Strategies to enhance Adherence and Health Outcomes

Volume 2 - Issue 1

Journal for Patient Compliance