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Volume 1 - Issue 2


Strategies to enhance Health Outcomes PEER REVIEWED

A Look at Medication Adherence Solutions What do consumers want in a medication adherence solution? Using Relationship Marketing to Drive Patient Adherence in a Chronic Disease State One size doesn’t fit all when it comes to adherence Fundamental progress in investigating drug resistance with electronic multidrug compliance monitoring (e-MCM)





Strategies to enhance Health Outcomes

DIRECTORS Mark A. Barker Martin Wright

Patient Story 8

PUBLISHER Clive Baigent MANAGING EDITOR Mark A. Barker EDITORIAL COORDINATOR Jaypreet Dhillon EDITORIAL ASSISTANTS Nick Love, Kevin Cross, Lanny McEnzie

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Adherence Happenings in the United States Wm. Ray Bullman, Executive Vice President of the National Council on Patient Information and Education (NCPIE), updates us on Adherence Happenings in the US with a focus on enhancing prescription medication adherence and promoting better health outcomes.


Adherence 360° : Can Healthy Nutrition Influence Patient Compliance? A lot of recent conversations have taken place around the relationship between treatment outcomes and good nutrition. But what exactly does this mean? Iulia Calota, a close collaborator of BIOAXIS Healthcare discusses this issue further in this article.


Internet/Technology and Patient Adherence As a follow-up to the first issue of the Journal for Patient Compliance, and the article entitled: “Creating a Value-added Packaging Design Using Web-enabled Smart Technology”, Chris Penfold, the CEO of Design Cognition Group Ltd, moves forwards and provides a regular Market Watch overview in each issue. In this article he provides thoughts and views on leading-edge areas of drug delivery, drug packaging, labelling and dispensing, with a particular emphasis on the internet and its interface with emerging technology.


From the Experts: The Latest Trends and Research in Adherence Hamish Franklin, Director of Europe, Atlantis Healthcare, writes that although much research and trail-blazing scientific knowledge goes into the development of a new drug, the fact is that it won’t work unless a patient actually takes it, as their healthcare practitioner prescribes. That’s why personalised patient support programmes are vital, says adherence solutions expert Jonny Duder from Atlantis Healthcare.


A Look at Medication Adherence Solutions Katrina Firlik, the co-founder and Chief Medical Officer of HealthPrize Technologies, considers: What do Consumers Want in a Medication Adherence Solution? The “patient-asconsumer” trend is here to stay, even though the consumer lens offers too restrictive a view when it comes to the complexities of healthcare. Navigating through chemotherapeutic options,

DESIGN DIRECTOR Ricky Elizabeth RESEARCH & CIRCULATION MANAGER Dorothy Brooks BUSINESS DEVELOPMENT Bryony Whittaker ADMINISTRATOR Petya Stefanova FRONT COVER © iStockphoto PUBLISHED BY Pharma Publications Building K, Unit 104 Tower Bridge Business Complex, 100 Clements Road, London, SE16 4DG, UK Tel: +44 0207 2375685 Fax: +44 0207 3947415 Email: Journal For Patient Compliance – Strategies to enhance Health Outcomes. ISSN 2045-9823 is published quarterly by PHARMAPUBS.

The opinions and views expressed by the authors in this magazine are not necessarily those of the Editor or the Publisher. Please note that although care is taken in preparation of this publication, the Editor and the Publisher are not responsible for opinions, views and inaccuracies in the articles. Great care is taken with regards to artwork supplied, the Publisher cannot be held responsible for any loss or damage incurred. This publication is protected by copyright. 2011 PHARMA PUBLICATIONS Volume 1 issue 2 (August 2011)

One Size Doesn’t Fit All when it comes to Adherence Grant Taylor, Director of Group Clinical Operations and Research at Atlantis Healthcare, examines issues such as ‘Forgetting’ is Not the Issue - Patients make a Choice, Why Tackling Non-Adherence is Vital to the Future of Healthcare, How Health Psychology Supports Patients, Why Qualified Nurse Support is Key, The All-Important Proof – Measuring Success, and The Face of Healthcare is Changing – Personalisation is the Key.

Journal For Patient Compliance Strategies to enhance Health Outcomes 1

Contents for example, is not exactly like picking a new car. Regardless, the consumer lens can be particularly enlightening when it comes to those certain “add-ons” in healthcare — those optional goods or services that patients-as-consumers either decide to engage with, or to ignore. Regulatory & Marketplace 22


Emerging Issues and Existing Obstacles to Providing Access to Medicines in Developing Countries Accessibility, Availability, Affordability and Acceptability of treatment are considered to be the most important issues for a successful therapy outcome. Each of these four issues can have a specific impact on patient compliance. Limitations in or lack of one or all of the above are considered to have a major impact on patients’ health, and not only in developing countries. In this article, Walburga Marder tries to identify the underlying causes, their impact on treatment outcome, and the challenges in addressing these issues. Using Prevalent Technology to Monitor and Improve Adherence A simple, patient-friendly solution based on smartphones could play a central role in improving adherence both in trials and in commercial use, argues Steven Carden and David Russell of PA Consulting Group, and Graham Howieson of GH Consulting. Behaviour Programmes


Family Ties – Educating and Engaging Caregivers for Retention Success In this detailed article Diana Anderson, President of DAC Patient Recruitment Services, explores Family Ties and the role of the caregiver. Whether family member or friend, the caregiver is the study participant’s partner in disease management and decision-making. He or she is, perhaps, the patient’s most important source of emotional and physi¬cal support — a role which can be both rewarding and demanding. Clinical Trials



interaction between pharma and patients which starts in the early phase of study development and extends throughout the ‘lifetime’ of a new drug or treatment. Therapeutic 38 Learning from Social Media about the Patient Journey and Adherence People with Alzheimer’s disease and their care partners are using social media to share their experiences with Alzheimer’s disease and treatment. This unfiltered exchange of information, suggests Chris Kelly, Director of Health Education at HealthEd, offers access to raw insights that can drive innovative solutions to overcome the challenges of adherence and improve outcomes for patients and healthcare providers (HCPs). 40 Case Study: Using Relationship Marketing to Drive Patient Adherence in a Chronic Disease State It has been stated in the pharmaceutical industry that the next big “blockbuster” might be patient adherence in a chronic condition. The problem is how the industry accomplishes that effectively and efficiently. Kevin Dunn, Vice President of Global Brand Strategy, asks how can it work? What is the process? What will the results be? 42 Fundamental Progress in Investigating Drug Resistance with Electronic Multidrug Compliance Monitoring (e-MCM) Current definitions of drug resistance are shaped by the pharmacotherapeutic fields they occurred in. They usually mention various contributing factors and refer either to the clinical or the biomarker level. Particular attention has been attracted by antiplatelet resistance, a phenomenon with clinical, cellular and pharmacogenetical contributors. However, the impact of every single factor to antiplatelet resistance in outpatients under prescribed antiplatelet therapy has not been comprehensively evaluated so far, neither has the temporal pattern of drug intake been studied as a possible contributor. By: Philipp N. Walter, Dimitrios A. Tsakiris, Michel Romanens, Willem Kort, Isabelle Arnet and Kurt E. Hersberger. Modern Technology

Effective ePRO Training Increases Patient Compliance and Yields Better Clinical Data Due to the increased demand for greater efficiency in clinical trials by both sponsors and CROs, Colin Cleary – a Program Manager with CRF Health – explores this critically important issue from several perspectives. In this article the author reviews the scientific literature to determine if there is a correlation between effective ePRO training and increased patient compliance in clinical trials.

48 Technology is Good for Your (and Pharma’s) Health In the run-up to eyeforpharma’s Flagship Patient Adherence event: 8th Annual Patient Adherence Communication and Engagement (PACE USA), and Patients Week 2011, Andrew Tolve of eyeforpharma reports on how pharma can leverage technology to build brand loyalty among physicians and patients.

Patient-Centred Clinical Trials Sjouke Huisman, co-founder of Clinical Study-Portal asks: How can Pharma Engage with Consumers on Product Development? How can Pharma Engage with Trial Subjects? The conclusion of this article is that enhancing patient engagement in clinical research should not be limited to patients participating in clinical trials. It is a process of

50 Inside the Mobile Health Jungle - How to Find the Best Path for Patient Compliance and Your Bottom Line For nearly a decade analysts have predicted mobile technologies would reshape the healthcare industry. During this period of analysis and debate, the safest place for a healthcare executive was as a spectator from a very safe distance. No healthcare organisation has yet conquered

2 Journal For Patient Compliance Strategies to enhance Health Outcomes

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Contents the mobile jungle. Adventures have been limited to a few exploratory pilots to test SMS messaging for compliance, some diabetes apps, and creative digital marketing scouting campaigns. Pamela Swingley of Mobile PRM discusses the future of technology in healthcare. Drug Delivery, Drug Packaging, Labelling & Dispensing 56

What Other Factors can Complement Packaging Design to Drive Greater Compliance? In this feature, Steve Kemp, of Brecon Pharmaceuticals Ltd, looks into the provision of scientific support for implementing new design ideas and stimulating a campaign for change in the packaging of pharmaceuticals across Europe. Case Study


A Hypertension Patient Support Programme in the Philippines to Improve Adherence and Outcomes Hypertension is a chronic, progressive cardiovascular disorder affecting 11.5 million Filipinos, according to recent data released by the Philippine Society of Hypertension (PSH). Despite this extensive prevalence, up to 25% of those affected are unaware of their condition. Statistics show that approximately 31% of patients with hypertension remain untreated, yet even in those who are treated, only 45% have it controlled. This means that blood pressure is not adequately controlled in the majority of adult patients with hypertension. Dr Saurabh Jain, Director- Patient Value Services of Indegene Lifesystems Pvt. Ltd, expands further in this article.


Folklore Emine Teyze and The Devil’s Machine By Nihat Akkaraca


JPC News

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And, of course, we all know the dire R&D predictions for the biopharma industry – no more blockbusters means lower profitability. In fact, biopharma is also finding an opportunity to improve financial outcomes while improving health outcomes through improved adherence. Kevin Dunn, of Global Brand Strategy (p.40) suggests the next blockbuster is patient adherence – an increasingly common opinion among manufacturers.

Volume 1 - Issue 2

     A Look at Medication Adherence Solutions What do consumers want in a medication adherence solution? Using Relationship Marketing to Drive Patient Adherence in a Chronic Disease State One size doesn’t fit all when it comes to adherence Fundamental progress in investigating drug resistance with electronic multidrug compliance monitoring (e-MCM)

With healthcare costs sky-rocketing all over the world, the payers – both public and private – are feeling the pressure. All are sorting out where to find efficiencies and improve margins. Ever so slowly, many organisations are looking to simply helping patients manage their health as a means to improve both health and financial outcomes.


Strategies to enhance Health Outcomes

Journal For Patient Compliance Strategies to enhance Health Outcomes

Finally industry – biopharma companies, health plans, government bodies – are paying attention to patient adherence. While it is true that these entities have paid some attention in the past there is evidence that a focus on non-adherence has gained momentum.

Volume 1 - Issue 2

This second issue of JPC continues the focus on compliance / nonadherence. Depending on where you are in the world the words “adherence” and “compliance” may or may not be interchangeable, but that is a discussion for another issue. The main point here is that the focus on the patient is finally becoming a reality. We are breaking old habits and making new ones to finally put the patient at the centre of our decision-making, of how we all do business. With this Foreword I will highlight just a few of the contributions you will find in this issue.

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15/8/11 20:10:18

Editorial Advisory Board Andree Bates, Managing Director, Eularis Anna Dirksen, Senior Manager, PSI Behavior Change Chris Penfold, Vice Chairman - East Midlands Packaging

So much in line with my own thinking is the concept that there is no single solution to improve adherence. In this issue several contributors reinforce the need for a multi-focal approach – Katrina Frilik, HealthPrize Technologies (p.20), Chris Kelly, HealthEd (p.38); Hamish Franklin, Atlantis Healthcare (p.16); Grant Taylor, Atlantis Healthcare (p.10); Ray Bullman, US National Council on Patient Information and Education (NCPIE) (p.12) – all share different perspectives on evolving patient needs and solutions appropriate across the patient journey, and how various techniques support patients across a continuum. The solutions, just like the overall approach, must be centred around the needs of the patient – and those needs change with circumstances the patients face at different stages in their lives.

Society, Consultant, Freelance Packaging Specialist Carole North, Managing Director, 90 TEN Healthcare Dyan Bryson, Managing Partner/VP Patient Strategy & Outcomes for Inspired Health Strategies Edwina Rogers, Executive Director of the Patient Centered Primary Care Collaborative Elisabeth Moench, President & CEO of Medici Global Helen Lawn, Managing Director, Helen Lawn & Associates a healthcare PR and communications agency Isabelle Moulon, Head of Medical Information Sector, European Medicines Agency

The healthcare industry is lagging behind the consumer goods industry in ensuring their end-user is at the centre of all decision-making. As the healthcare industry is taking small steps to test the theory that truly putting the patient at the centre can also aid the bottom line, the theory is being put into practice at the very foundation of the biopharma sector in R&D. Sjouke Huisman of Clinical Study Portal (p.36) provides an enlightening perspective on building a relationship with a patient as early as actual study development. As our consumer goods colleagues would argue, building a lifetime relationship can be valuable to both patient and manufacturer. If the patient was at the centre in the beginning of the product lifecycle and all parts of the organisation are in lock step with this approach – especially R&D, marketing, sales – there would be less redundancy in the organisation and improved health and financial outcomes in the end.

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

Further supporting the notion of putting the patient at the centre is Diana Anderson, DAC Patient Recruitment Services (p.30) discussing the role of the care-giver in reinforcing positive patient behaviour. The care-giver is often overlooked by the formal healthcare system and industry, but the care-giver is one of the most influential people in the life of the patient.

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

With this second issue, JPC continues to harness the thinking that has been long held captive in disparate silos all around the world. To advance science, researchers collaborate across country and academic borders, across functional responsibilities. We can follow this example. Improvement in patient adherence or compliance will only happen if we work across all of our silos and put the patient at the centre of everything we do.

Services and CME Solutions at Indegene. Steve Kemp, Business Development Director at Brecon Pharmaceuticals and Vice-Chairman of HCPC Europe Tassilo Korab, Co-founder of HCPC Europe (Healthcare Packaging Council) Vassilis Triantopoulos, CEO of BIOAXIS Healthcare

Dyan Bryson, Managing Partner/VP Patient Strategy & Outcomes for Inspired Health Strategies 6 Journal For Patient Compliance Strategies to enhance Health Outcomes

Walter Berghahn, Executive Director, The Healthcare Compliance Packaging Council Volume 1 - Issue 2

Patient Story

One Size Doesn’t Fit All when it comes to Adherence Patients aren’t just ‘forgetting’ to stick to their medication; they are choosing not to use it – and they are far from alone. ”70% of patients who do not stick to their treatment plan are intentionally non-adherent, according to the latest health psychology research,” says Professor John Weinman, world-leading Adherence Researcher. “When you consider that each patient is living an individual life, and has personal attitudes to their condition and treatment that determine why they choose not to take their medication, it becomes clear that traditional adherence programmes based on ‘reminders’ are not tackling the root of the problem. A reminder is not going to change someone’s mind about their treatment if they have decided – even subconsciously - not to take it. And it’s clear that however effective a drug has been proved to be, it won’t work unless a patient takes it, for the period of time their healthcare practitioner has prescribed it – and in the right dose, at the right intervals.” Why Tackling Non-Adherence is Vital to the Future of Healthcare In Europe alone it is estimated that £125 billion has been lost due to non-adherence. Looking at the US, avoidable medical spending was estimated at $300 billion in 2009 due to patient non-adherence. And it is thought that non-adherence results in an average per-drug loss of 36% in potential sales for a pharmaceutical company1. And cost is not the only issue – patients who don’t use their medicines compromise their health and quality of life, contribute to decreased workplace productivity, and have an increased chance of relapse. Average adherence rates amongst Cancer patients is 62%, while those with Parkinson’s disease are closer to 60%2. For clinicians, non-adherence contributes to issues such as stretched hospital resources, reduced efficacy of treatment regimens, and poorer long-term patient health outcomes - to name only a few. In a world where the population is generally ageing, and epidemics such as obesity, heart disease, diabetes and dementia are creating a huge future need for resources; nonadherence is not just an issue around prescribed medication. It also applies to recommended lifestyle changes such as exercise, healthy eating, quitting smoking and sensible alcohol consumption, making non-adherence a massive issue for any health system to tackle. Which researchers have been successful in addressing nonadherence? While there is no easy fix to non-adherence, the new discipline of health psychology has been generating some crucial insights that have enabled real advances in the development of 8 Journal For Patient Compliance Strategies to enhance Health Outcomes

effective solutions, in the shape of personalised interventions designed to increase adherence to therapy. There are an emerging set of research tools that have been well validated across multiple disease states as being effective not only in predicting non-adherence, but also in informing interventions to improve adherence to treatment. To understand how these research tools are used with patients, let’s look at three different persona’s to understand how individual beliefs can affect the way prescribed medication is taken. Meet Janet. She is 67, lives in Chester, has two grandchildren, loves Wednesday mornings because she has walking club with her friends, and is an avid fan of natural remedies. In 2009 she was shocked by a diagnosis of breast cancer, and a prescription of hormonal therapy medication from her oncologist. She hates the idea of taking a pill every day and is considering using healthy living and natural remedies as an alternative – she reassures herself that this will surely be an effective substitute. Tony, on the other hand, had a heart attack at age 52, and despite the near-death experience is struggling to take his medication because it reminds him every day of how ill he’s been. He hates being seen as an invalid by his wife of 26 years, Karen, and he bridles at the thought of being told what to do by healthcare practitioners, even though he knows they have his best interests at heart. Minal, 34, is sick of her psoriasis stopping her wearing the clothes she loves, but is so determined not to let it rule her life that she organises regular nights out with friends. Often, that means she just can’t be bothered using her prescribed ointment after a night out when she has to be up early for work the next day. Looking at Janet’s story, we can discover how health psychology insights and personalised interventions helped during her journey, as she came to terms with her breast cancer diagnosis, and medication prescription. She deliberated long and hard over whether she should take this medication. She asked friends for their thoughts, looked for online reviews, and tried contacting her oncologist for further information – but no-one had the answers she needed. A few days into her prescription, she took out a packet of her medication, and when she opened the pack, an insert fell out recommending a support programme for people prescribed this medication. Hopeful of finding out more about her treatment plan, she visited the website and enrolled in the relevant support programme. Within three days of submitting an enrolment, she received a phone call from a registered nurse who encouraged her to ask questions about her medication and breast cancer diagnosis. They discussed her concerns and the nurse went Volume 1 - Issue 2

Patient Story through a number of questions with Janet surrounding her opinions on the medication plan. These questions are part of a scientific questionnaire called the Beliefs about Medicine Questionnaire (BMQ). Going through this is a crucial step in understanding each patient and their attitudes to their condition, and medication3. “This BMQ tool has been shown to be a reliable and valid method of assessing cognitive representations of medication, and therefore revealing what patients believe about their medication, and their associated risk of nonadherence,” says Professor John Weinman who is presently the Head of Health Psychology, Institute of Psychiatry, Kings College London. Professor Weinman co-developed the BMQ, which has been cited and used successfully across a range of conditions and medications, including: hypertension (Ross, Walker & MacLeod, 2004); HIV/AIDS (Gonzalez et al., 2007); rheumatoid arthritis (Neame & Hammond, 2005) and breast cancer (Grunfeld et al., 2005). The Beliefs about Medicine Questionnaire (BMQ) – in detail Professor John Weinman explains how this tool is key to unlocking the real reasons behind a patient’s non-adherence: “The BMQ enables us to reliably identify beliefs held by the patient that are predictive of non-adherence. Once we have identified those beliefs, we can then understand which are ‘unhelpful’ (as it relates to adherence) and set about intervening to change those unhelpful beliefs”. The BMQ comprises two 5-item factors assessing beliefs about the necessity of medication and concerns about prescribed medication in relation to; long term toxicity, danger of dependence and the disruptive effects of medicine. Patients are asked to rate how strongly they agree with statements related to their prescribed medication using a 5-point Likert scale (1=Strongly Disagree, 2=Disagree, 3=Uncertain, 4=Agree, 5=Strongly Agree). The questionnaire can be amended for specific medications. 4

Horne, R., Weinman, J. & Hankins, M. (1999).

Personalised Interventions Tackle Unhelpful Beliefs At the end of her BMQ call, Janet felt relieved and comforted, as well as more at ease about taking her medication, although she still had a few minor concerns. What outcomes have other people on this medication seen? Had it actually made a difference in their quality of life? This phone call was the first step to personalising the support programme for Janet. From her answers, the nurse could assess her “adherence risk profile”, in order to tailor the patient support programme to her needs. With an insight to Janet’s personal beliefs, tailored communications can now be designed to help answer her questions and challenge the unhelpful beliefs about her medication – commonly known as ‘interventions’. Janet’s Personalised Interventions A week after Janet’s initial chat with the nurse, she received a text message (SMS) encouraging her to visit a website that had more information about the realities of living with breast cancer. Apparently, one in eight women will contract some form of breast cancer in her lifetime, and the most effective forms of treatment involve both surgery and medication. A few weeks later she received a magazine in the post, which contained interviews with other women coping with breast cancer, plus practical advice to help her cope with the day-to-day issues she was facing. One of the ladies profiled had been diagnosed with stage IIIB breast cancer – a group of patients that have a survival rate of approximately 54 per cent. Five years on from her diagnosis, this lady was 10 Journal For Patient Compliance Strategies to enhance Health Outcomes

going strong; she attributed this to living a well-balanced, healthy lifestyle in conjunction with sticking diligently to her medication plan. Interesting – ‘so maybe a healthy lifestyle won’t be enough,’ considered Janet5. Two weeks later, she received a follow-up call from a nurse to ask how the treatment plan was going and find out how she was feeling about it. Janet was encouraged to call a nurse support team via an 1800 phone line if she had any questions. In short, she found the support programme truly valuable (see box copy, below). ‘My breast cancer support programme really helped’ After a year on a personalised patient support programme, Janet* made the following comments to the nurse she had contact with; “I need to tell you that you have made a difference in my life. You helped me by really listening to my cry for help. You told me that I should not shut out emotional support. You told me there was a greater need to manage my pain better and not give up. You gave me honesty, clarity and hope in my moments of deep despair. You were there for me when I needed a reality check and some sound advice.” Atlantis Healthcare (2007). Verve programme case study. Patient letter. *Not her real name

Why Qualified Nurse Support is Key Elizabeth Akinwumi is a Senior Nurse Advisor who provides support and advice for a variety of patients. She explains that each patient support programme they deliver is different – tailored to the disease state and the unique needs of each patient. “Patients want to know they are talking to a qualified health professional who not only has knowledge about their disease but understands the social, psychological and emotional implications of their disease. There’s a certain rapport you build with patients over the phone that encourages open dialogue, where patients feel like they are really being listened to as well as supported. And it is through this open dialogue that a patient reveals factors that may affect their ability to comply with their prescribed health regime.” It is the nurse’s role to use their clinical expertise and medical knowledge to support patients during their treatment journeys. The All-Important Proof – Measuring Success There is a growing body of evidence demonstrating the success of personalised interventions to change people’s illness and medicines beliefs – thereby changing their adherence behaviour. With published papers in Breast Cancer and Asthma, and rigorous case studies in Osteoporosis, Alzheimer’s Disease and Prostate Cancer, the effectiveness of this approach to intervention is proving popular with those organisations develop Patient Support and Disease Management programmes. While personalised interventions are proven to help patients through their treatment journeys, it is crucial to understand that they do deliver tangible results in increasing adherence to therapy. Janet enrolled in a measured breast cancer patient support programme, where enrolled patient outcomes were observed and compared to those in a non-intervention group - where the patients did not receive any support. Janet’s outcomes are similar to the average recorded in the intervention group – where patient support was provided. Volume 1 - Issue 2

Patient Story Compared to the non-intervention group of patients, Janet recorded a 23% lift in medicines use, a 33% increase in persistence in taking her medication, improved understanding of side-effect management, and an additional lift of script fulfilment by 2.2 per year6. Asthma Aim Case Study The Issue - 25% of asthma patients have poor disease control; this is strongly associated with non-adherence which has been proven to be as high as 50%. - The economic impact of non-adherence is significant, with uncontrolled asthma patients costing £381 per year vs. £108 for controlled. Solution - An evidenced-based and highly scalable programme in the form of a randomised controlled trial - designed to increase levels of adherence to asthma preventer medication. - Individuals were assigned to either the intervention or control arm of the study. - Individuals in the intervention arm receive an 18-week text messaging programme. - Text messages (SMS) are tailored to the individual and address the beliefs that are associated with non-adherence to asthma preventer medication. - Individuals are followed up at five timepoints over a nine-month period. Outcomes - Adherence rates were captured via patient self-report and ‘smartinhaler’ data. - The group of patients who were allocated to the 18-week SMS intervention achieved a 40% lift in adherence to preventative therapy over baseline. - Adherence gains were still evident six months after the intervention had ceased. - Illness perceptions and medicines beliefs were changed as a result of the intervention, and these changes persisted after the intervention ceased. Atlantis Healthcare (2011). Case study - Increasing adherence in Asthma by targeting patient belief.

Personalisation is the Key to Adherence Let’s take a step back and look at the wider issue of medication adherence. It takes approximately ten years to research a molecule – the first step to creating a drug. Then on average this drug will take five years to enter the market…then add on another two years to convince healthcare practitioners to recommend it to patients. It finally hits the market - and it flops because patients aren’t taking it correctly. This is a nightmare for pharmaceutical businesses, payers and clinicians - especially in a competitive market where medicines increasingly must be shown to provide value. All patients have individual beliefs which affect the way they make decisions about taking their medication. Personalised patient support programmes are now a must.

beliefs. Journal of Human Hypertension, 18, 607 – 613. Grunfeld, E.A., Hunter, M.S., Sikka, P. & Mittal, S. Adherence beliefs among breast cancer patients taking Tamoxifen. Patient Education and Counselling, 59 (1), 97 – 102. 4. Horne, R., Weinman, J. & Hankins, M. (1999). The Beliefs about Medicines Questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medication. Psychology and Health, 14, 1-24. 5. Breast Cancer Society. factsandstatistics/breastcancerfacts.shtml. Retrieved 22 July, 2011. 6. Atlantis Healthcare (2007). Verve programme case study.

Grant Taylor, MSc(Hons), PGDipClinPsych, FNZCCP Director of Group Clinical and Research Grant is responsible for policy and procedures governing the work of the Atlantis Healthcare clinical team globally, leads the internal product development processes for the business as a whole and is responsible for the Atlantis Research Institute. Prior to joining Atlantis, he set up and led a national child helpline in New Zealand. Grant is registered in New Zealand as a clinical psychologist and he has a career spanning more than 30 years in clinical and health psychology. He has specialist experience in mental health, respiratory disease, chronic illness management, orthopaedics, chronic pain management and obesity management. Email:

References: 1&2. Cap Gemini. (2011). Patient Adherence: The Next Frontier in Patient Care. 3. Gonzalez, J.S., Penedo, F.J., Llabre, M.M., Duran, R., Antoni, M., Schneiderman, N. & Horne, R. (2007). Physical Symptoms, beliefs about medications, negative mood, and long term HIV medication adherence. Annals of Behavioural Medicine, 34 (1), 46-55. Neame, R. & Hammond, A. (2005). Beliefs about medications: a questionnaire survey of people with rheumatoid arthritis. Rheumatology, 44 (6), 762 – 767. Ross, S., Walker, A. & MacLeod, M.J. (2004). Patient compliance in hypertension: role of illness perceptions and treatment

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Watch Pages

Adherence Happenings in the US Seizing the Day In the nearly 30 years that I have worked for the National Council on Patient Information and Education (NCPIE) – a USbased not-for-profit coalition committed to promoting safe and appropriate medicine use – never can I recall more attention being paid to enhancing prescription medication adherence and promoting better health outcomes. This is good news. A few cases in point follow below. • The National Alliance of State Pharmacy Associations (NASPA) is currently reviewing proposals from state pharmacy associations seeking to identify ways in which pharmacists can assist patients to improve adherence. Selected projects are intended to produce measurable, scalable, replicable and sustainable programmes in community pharmacy to improve adherence or methods to identify non-adherent patients. • The National Association of Chain Drug Stores Foundation is currently reviewing proposal submissions addressing primary medication non-adherence (PMN) – the failure of a patient to obtain a new medication which their healthcare provider has prescribed. • The National Institute of Health Office of Behavioral and Social Sciences Research (OBSSR) and the NIH Adherence Research Network recently circulated a request for information (RFI) seeking input from the scientific community, health professionals, patient advocates, community-based organisations, students and the general public about current and emerging priorities in adherence research that offer the greatest potential for improving the nation’s health and wellbeing. What did they learn from the 63 responses from researchers, professional societies and practitioners? • Improve measurement science – improve and/or move beyond self-report (“subjective”) measures toward greater use of “objective” adherence measures and biological outcomes. • Intervention utility/feasibility – develop and test adherence interventions that are feasible within busy clinic settings and that have clear utility for clinicians and members of comprehensive treatment teams. • Intervention target outcomes/populations – focus on patients who are taking multiple medications for multiple, concurrent co-morbid conditions. • Adherence determinants – need to better understand specific adherence challenges (e.g., depression, mental illness, cognitive decline, incarceration, stigma, treatment factors). • The New England Healthcare Institute (NEHI) will convene “Road Map to Improved Medication Adherence” on September 22, 2011 in Washington, DC. Details: http:// medication_adherence • The National Consumers League (NCL) recently launched a national public education campaign, Script Your Future, to raise awareness among patients about the consequences of not taking medication as directed. The centrepiece of the 12 Journal For Patient Compliance Strategies to enhance Health Outcomes

multi-year campaign is a website,, which provides tools to support patient efforts to adhere to their prescribed medicine. Tools include free text message reminders, sample questions, medication lists and charts to keep track of medicines, and fact sheets on common chronic conditions such as diabetes, asthma and high blood pressure. A companion campaign site with adherence tools for healthcare professionals is also available at http:// NCPIE Tools You Can Use: 1. Enhancing Prescription Medicine Adherence: A National Action Plan (free download @ enhancing_prescription_medicine_adherence.pdf 2. Your Medicine. Be Smart. Be Safe. @ educational_resources.jsp Answers common questions about getting and taking medicines and has handy forms to help keep track of information. Includes four important ways to be smart and safe with medicines. Available in Spanish Language. 1. Give your healthcare team important information. 2. Get the facts about your medicine. 3. Stay with your treatment plan. 4. Keep a record of your medicines. Relevant Web Links: 1. The National Alliance of State Pharmacy Associations (NASPA) - 2. The National Association of Chain Drug Stores Foundation - 3. The National Institute of Health Office of Behavioral and Social Sciences Research (OBSSR) and the NIH Adherence Research Network - scientific_areas/health_behaviour/adherence/adherenceres earchnetwork.aspx 4. The New England Healthcare Institute (NEHI) medication_adherence 5. National Consumers League - and Script Your Future Medication Adherence Campaign 6. National Council on Patient Information and Education (NCPIE) – Mr. Bullman joined the National Council on Patient Information and Education (NCPIE) in 1985. He has served as Executive Vice President since January 1995. NCPIE, organised in 1982, is a non-profit coalition of diverse member organisations working together to stimulate and improve communication of information on safe and appropriate use of medicine to consumers and health care professionals. Email:

Volume 1 - Issue 2

Watch Pages Adherence 360°

Can Healthy Nutrition Influence Patient Compliance? A lot of recent conversations have taken place around the relationship between treatment outcomes and good nutrition. But what exactly does this mean? A healthy diet should contain food from all the major food groups to give us the nutrients and the energy we need in order to perform daily tasks and keep our bodies functioning. Complete nutrition is essential for all the body’s functions, and it sustains our immune system to fight against illness. Every single cell in our body is built from protein – including muscle, bone, cartilage, skin, blood, fingernails, hair, cell membranes, hormones – while fats and sugars provide energy, insulation and support for the body. What happens though when someone is under treatment for a chronic condition or is recovering after illness or surgery? Does their diet need to adapt to their treatment requirements, do they require a supplementation of certain nutrients or vitamins in order to optimise the outcomes of their medication? The general consensus is that compliance to treatment does not solely mean taking the medication as prescribed, but making dietary and lifestyle changes. Whilst this is quite an obvious statement for conditions such as diabetes or liver disease where a special diet is compulsory as part of the treatment, there is a large number of conditions and circumstances where a change in nutrition is desirable for an optimal outcome of treatment to take place. In fact, in recent years, more and more thought has been given to a whole new therapeutic area, sometimes found under the name of Medical Nutrition Therapy (MNT). MNT refers to the assessment of the nutritional status of patients with an illness, diet-related condition, or injury, in order to benefit the patient’s health and reduce healthcare costs. The purpose of MNT is to identify patients at risk of major nutritionrelated health problems and recommend dietary adjustments leading to better health outcomes and improved quality of life. This type of therapy includes developing a specialised nutrition prescription that includes patient education and self-management training. Also called therapeutic nutrition, MNT has become an increasingly important component of integrated healthcare systems. A few recent clinical trials have demonstrated a significant improvement in medical and clinical outcomes with the help of nutritional therapy, as is the case, for example, with patients suffering from diabetes mellitus. As seen, MNT is a therapy in its own right, but in many cases an educated change in diet can be self-managed, with great impact on treatment outcomes and compliance. It is well known that certain disease areas imply a special diet, such as is the case with osteoporosis patients who require an additional intake of calcium-high foods and vitamin D for their treatment to have maximum success rate. Heart disease patients are usually required to limit the amount of cholesterol-high foods in their diet, while people diagnosed with Alzheimer’s disease 14 Journal For Patient Compliance Strategies to enhance Health Outcomes

are recommended to eat lots of foods high in Omega-3 and antioxidants. Scientists claims that a diet high in Omega-3 fatty acids can also help prevent obesity and a range of health issues and complications like heart problems, diabetes, autoimmune disease, and arthritis problems. But generally speaking, a sustained intake of nutrients necessary to cellular renewal can be a powerful catalyst to optimal recovery. Whilst all of the above provide a link between a healthy diet and optimal treatment outcomes, it is also interesting to know how much nutritional intervention and education has a notable influence over compliance to the treatment. A study on treatment compliance and lifestyle modifications in COPD patients revealed that lifestyle advice from healthcare professionals was poor, and that patients required better education to manage their disease effectively. At present, there is only a small body of evidence to prove the direct effect of healthy nutrition on treatment compliance, and perhaps more research should be conducted in this direction. Conclusive results might prove to have a significant impact on the management of patient compliance. Considering that some of the positive effects of an adequate diet during treatment may include minimising drug side-effects, lowering the level of illness-related fatigue and helping with faster recovery, it is somehow safe to assume that a nutritional intervention alongside treatment may improve patient compliance and recovery – perhaps something worth keeping in mind. Sources: 1. w, [accessed July 2011]; 2. Franz, M et al, Effectiveness of Medical Nutrition Therapy Provided by Dietitians in the Management of Non-Insulin-Dependent Diabetes Mellitus, 1995; 3. Jones, M. et al, A qualitative study of compliance with medication and lifestyle modifications in COPD patients, 2004 Iulia Calota specialised in healthcare communications and a player in the field of adherence providers, Iulia Calota is a close collaborator of BIOAXIS Healthcare. Essentially a marketing communications professional with a global approach and having worked in the global communications and localisation sector for important pharma clients, Iulia’s view is always integrated. Recently involved in medical nutrition projects, she also has a genuine interest in putting forward new methods and approaches to enhancing patient compliance. Email:

Volume 1 - Issue 2

Watch Pages

Internet/Technology and Patient Adherence In the first issue of the Journal for Patient Compliance I wrote an article entitled: “Creating a Value-added Packaging Design Using Web-enabled Smart Technology”. Moving forwards I will be providing a regular Market Watch overview in each issue of the Journal for Patient Compliance. I will provide my thoughts and views on leading-edge areas of drug delivery, drug packaging, labelling and dispensing, with a particular emphasis on the internet and its interface with emerging technology. But what do you want? What interests you? If you come across any areas that you feel may be of interest to other readers, are developing concepts yourself, either as a supplier or a producer/packer/filler/marketer, let me know and I will try to incorporate them. In my recent article I highlighted the explosion in web and ‘intelligent’ material technology which is bringing us evercloser to the scenario set out in the 2002 film Minority Report, which painted a picture of life in 2054 where computers are operated by voice and gestures, newspapers interact with their readers, animated billboards interact in a personalised manner with consumers as they walk by, using iris-recognition technology, and cornflakes packets bearing irritating sounds and pictures keep the kids amused. I also highlighted the importance of identifying, anticipating, designing for and meeting consumer needs based on identified insights, where for maximum consumer satisfaction and corporate profit, each ‘niche’ will benefit from suitably designed packaging solutions. I went on to talk about a number of areas of leading-edge technology that are already making huge inroads into the healthcare sector to improve patient adherence and hence improve their lives. Innovations are evolving all of the time, and since writing that article, further exciting improvements have been made, incorporating all of the above and highlighted by the following recent awards. Some Recent Innovations of Note The Healthcare Compliance Packaging Council (HCPC) recently held its annual Compliance Package of the Year competition on May 3rd at RxAdherence 2011, the organisation’s annual conference on patient adherence and compliance packaging, demonstrating the huge ongoing development effort in this important area of healthcare packaging. The competition consists of two categories: one for trade packages released in the past year and the other for innovative designs not yet available commercially. Winning for Innovative Design was the DelPouch® Starter Kit by Catalent Pharma Solutions, recognised for providing a unique packaging solution that may help to enhance a patient’s experience and to promote adherence to a regimen of topical treatments. The kit incorporates multiple adherence drivers, such as the DelPouch unit-dose delivery system, the connectivity of Catalent’s Media Enhanced Packaging™ technology and reminder-prompting configurations. It was designed ‘from the ground up’ to contain several features that improve a patient’s experience. Among these features is the unit-dose topical treatment design of the 16 Journal For Patient Compliance Strategies to enhance Health Outcomes

DelPouch® package itself. This unique delivery vehicle delivers the right amount of treatment to an affected area in a safe and convenient manner. The package also features Catalent’s Media Enhanced Packaging™ technology which offers a patient a gateway to specific, product-centred content via the internet, a smartphone application and an embedded watermark built right into the package. Brands can leverage this technology to deliver product-specific content, video instructions in multiple languages or even special offers, all without consuming valuable packaging space. Finally, the design includes several passive engagement devices which can be used to enhance a patient’s experience. These range from the way the package itself is constructed to provide reminder prompting through day/night graphics and printing of the days of the week, to increased billboard space which will allow physicians to provide notes or additional educational information, empowering a patient to manage their own medication regimen. Having been released recently, Novartis Pharmaceuticals’ Diovan HCT® Shellpak® was named 2010 Compliance Package of the Year (CPY). Submitted by Anderson Packaging on Novartis’ behalf, the pack features 30 days of treatment in a calendarised unit-dose blister. To facilitate compliance with the medication regimen, tablets are laid out with colour-coded days and weeks, including reminders for refilling the prescription. The 30-day blister is contained in the 170mm Shellpak outer, patented child-resistant package design from MeadWestvaco. The rigid plastic design features a front and back label. The back label provides a designated area for the patient’s prescription label as well as an adhered prescription insert. The front of the pack features an extended-content booklet label, including a photograph of the pill. Multiple pages within the front label provide patients assistance with dosing instructions, guides to joining the BP Success Zone Program including the website, toll-free phone number and additional regulatory information. The Shellpak is offered in four strength combinations, each of which features a distinctive colour (brown, blue, purple, red) and photograph of the unique tablet design for each strength to ensure correct dosing for the patient. The CPY runner-up was awarded to the Somaxon® Volume 1 - Issue 2

Watch Pages Pharmaceuticals’ Silenor® Patient Starter Kit. Also submitted by Anderson Packaging, on Somaxon’s behalf, the Silenor Patient Starter Kit’s carton is innovatively designed so that when opened, it resembles a bedroom complete with bed and nightstand. Contained within the design is a seven-count unit-dose carded blister, removable from the design to enable portability and convenience. To support patient compliance and adherence, the bed carton design contains a literature pocket, housing the medication guide, the Sleep-Saver™ Program prescription discount card, and a multi-panel colour leaflet complete with instructions on taking the product, description of side-effects, guides to enrolling in the Sleep-Saver Program, including website and toll-free phone number, as well as additional information on insomnia treatment. Finally, the CPY third-place runner-up was earned by Three Rivers Pharmaceuticals’ Ribasphere® Ribapak for Ribavirin tablets, which is indicated for the treatment of adults with chronic hepatitis C virus infection, and reported as the only form of ribavirin available in a daily, two-pill compliance package designed to enhance therapy adherence. Patients take only two tablets each day — one in the morning and one at night — instead of up to six, reducing the number of pills taken over 24 or 48 weeks of treatment. RibaPak packaging is clearly marked for seven days of am and pm dosing, and the completion of a compliance pack reminds the patient to administer their accompanying weekly interferon therapy, helping the patient adhere to his or her treatment. The

package insert includes full prescribing information, as well as warnings, adverse reactions, dosage and administration details. Packaging was done by Sharp Corp. 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.,, Email:

Watch Pages

From the Experts: The Latest Trends and Research in Adherence However much research and trail-blazing scientific knowledge goes into the development of a new drug, the fact is that it won’t work unless a patient actually takes it, as their healthcare practitioner prescribes. That’s why personalised patient support programmes are vital, says adherence solutions expert Jonny Duder from Atlantis Healthcare. Atlantis’s unique evidence-based insights into patient behaviours form the basis of their upcoming presentation at October’s Patient Adherence Communication and Engagement (PACE) Summit in Philadelphia, USA. Non-adherence to medication is a widespread issue that has concerning global consequences; it is estimated that 125,000 lives and $300 billion is lost every year in America due to non-adherence. The resounding importance of addressing this prolific issue is vital, but unfortunately it’s not an easy one to solve. Starting at Ground Level with Individual Patients “The individualised belief-based approach pioneered by Atlantis is moving into the mainstream of pharmaceutical industry thinking,” says the Global Solutions Managing Director, Jonny Duder. “It is the Atlantis idea that improving adherence requires individual patients to change their behaviour for the long term, and that to create that change you need to understand each and every patient’s beliefs and attitudes that drive his or her behaviour. It was encouraging to see this idea resonate with other delegates at the previous eyeforpharma Berlin PACE conference earlier this year,” he says. But what exactly is an ‘individualised belief-based’ approach? And why is personalisation the key to success in adherence programmes? “Health psychology research reveals over 70 per cent of non-adherence is in fact intentional,” says Professor John Weinman, Professor of Psychology as applied to Medicine, Institute of Psychiatry, King’s College London, and Head of Health Psychology, Atlantis Healthcare. “The key to influencing long-term behaviour lies in understanding the drivers of non-adherence for each individual,” he says. “Our research has shown us that beliefs – beliefs about the illness and beliefs about the treatment – are the best predictors of non-adherence. We can tell which beliefs are helpful for adherent behaviour – and which are unhelpful, in that they drive non-adherence. On this basis, we can identify those unhelpful beliefs, and intervene to correct, or modify, each individual’s ‘unhelpful’ beliefs.” Traditional Patient Support Programmes Aren’t Good Enough “Traditional interventions, mass reminders and the like, are only likely to be effective with those who are unintentionally non-adherent,” explains John. “Our focus has always been on addressing both the intentional and non-intentional non-adherence – so we have 18 Journal For Patient Compliance Strategies to enhance Health Outcomes

to recognise those who make the conscious decision not to adhere to their prescribed treatment. As pharmaceutical companies increasingly see adherence as a tool to ensure optimal outcomes for their medications, they need to refocus their efforts on engaging with that group of patients that are intentionally non-adherent as well” says Jonny. An effective patient support programme should utilise a combination of assessment, message, frequency, timeliness and channel to deliver interventions that resonate with patients on an individual level to change long-term behaviour. To achieve this Atlantis have built up a global team of worldleading health psychologists that specialise in adherence, Volume 1 - Issue 2

Watch Pages

The BMQ has been cited in more than one thousand published works has proven again and again to be effective in predicting medicines non-adherence. The diversity of disease states makes for interesting reading, and recent noteworthy studies include; hypertension (Ross, Walker & MacLeod, 2004); HIV/AIDS (Gonzalez et al., 2007); rheumatoid arthritis (Neame & Hammond, 2005) and breast cancer (Grunfeld et al., 2005). Delegates to the PACE US conference will be able to share in these insights as Professor Weinman and Jonny Duder address them in their keynote presentations. Other developments unfolding in the adherence industry will also be discussed, such as the emerging trend amongst pharmaceutical businesses to utilise global structures that support localised patient support programmes. Adherence Goes Global Duder explains; “There is a trend from country-specific patient support programmes towards best practice solutions that range across a number of markets. Companies want to have the ability to roll out regional or even global patient programmes, and monitor effectiveness, whilst at the same time allowing the affiliate the flexibility to ensure market needs are met. So how can a global solution be delivered to ensure patients are treated as individuals, and the programme is personalised? “Programmes need to be able to be tailored to take into account different patient and healthcare professional attitudes and cultural drivers, not to mention the funding environment,” says Duder. “The ability to meet global business objectives with local solutions tailored to meet the needs of the individual markets is vital to delivering global adherence solutions in today’s market. Interestingly, the core intervention is typically very similar, as adherence challenges market to market are most often consistent. It is how the programme is executed in terms of positioning, HCP engagement, regulatory compliance, and integration into the healthcare system that market tailoring becomes critically important.” The PACE US summit will include other speakers who specialise in patient adherence, making this event a mustattend for those with a vested interest in this growing industry. to ensure that only robust evidence is applied in creating effective, personalised programmes that drive individual behaviour change. This is the theory – but does it work? Research methods have been established over the past twenty years, designed to assess patient’s beliefs about their prescribed medication. “The Beliefs about Medicine Questionnaire (BMQ) has been shown to be a reliable and valid method of assessing patients’ beliefs about their prescribed medication, and therefore revealing their associated risk of non-adherence,” says John Weinman, Professor of Psychology as applied to Medicine, Institute of Psychiatry, King’s College London.

Hamish Franklin Director of Europe, Atlantis Healthcare Hamish has over 15 years’ experience in relationship marketing and has spent the last six years working in patient communication and support. Hamish is an expert in ensuring patient programs are delivering their strategic goals and have the operational and technical infrastructure to make them work. Hamish became a director of Atlantis Healthcare in 2002 and has won numerous awards for loyalty, relationship marketing and patient support programs. Email: Journal For Patient Compliance Strategies to enhance Health Outcomes 19

Watch Pages

What do Consumers Want in a Medication Adherence Solution? The “patient-as-consumer” trend is here to stay, even though the consumer lens offers too restrictive a view when it comes to the complexities of healthcare. Navigating through chemotherapeutic options, for example, is not exactly like picking a new car. Regardless, the consumer lens can be particularly enlightening when it comes to those certain “addons” in healthcare — those optional goods or services that patients-as-consumers either decide to engage with, or to ignore. Consider the recent push to boost medication adherence rates. Given the overwhelming public health and corporate implications of non-compliance, a wide variety of tactics are being pursued by payors, pharmaceutical companies, PBMs and pharmacies, with increasing urgency. As far as I am concerned, the more tactics out there, the better. There are no “one size fits all” or “silver bullet” approaches, as any adherence expert would attest to. That said, given the plethora of tactics out there, I am surprised at how few attempts have been made to ask consumers what they would actually want in an adherence solution. I say that because so much depends upon what the consumer actually wants. A well-intentioned and expertly crafted adherence solution will only work in the real world if people actually want to use it, and can easily grasp its benefits. It won’t work if people don’t opt in or aren’t inspired to engage (think Google Health). So why not find out what entices people most? As co-founder and chief medical officer of HealthPrize Technologies, a company with a rewards-based adherence platform, I was curious to test the waters. Although our system incorporates education and reminders, it is, at its heart, a rewards-based loyalty programme. The more you stick with your medication, the more points you earn. This simple scheme works nicely for credit card companies, hotel chains, and airlines. But would patients be turned off by the idea of earning points for taking their statin? Shouldn’t the intrinsic reward of good or improved health — preventing a heart attack or stroke — be enough? Would consumers act so predictably when it comes to medication adherence, a complicated and multi-faceted phenomenon? There must be a big difference between racking up Marriott points and earning “statin points”, right? So, in collaboration with our partner RealAge (a leading health and wellness website), we surveyed over 900 people who take at least one prescription medication for a chronic condition, and we asked them what types of medication adherence solutions they would be most likely to try. We allowed them to select as many options as they wished. Here are the results: In-person pharmacist-based programme: 6 per cent Phone call reminder programme: 14 per cent Online education programme: 15 per cent Text message reminder programme: 18 per cent Email reminder programme: 46 per cent Rewards-based programme: 70 per cent The respondents were largely women (84 per cent) and 20 Journal For Patient Compliance Strategies to enhance Health Outcomes

the majority (86 per cent) were aged 45 or above. Patients on Medicare or Medicaid were excluded from the study to mimic real world restrictions (government restrictions prohibit any form of financial incentive to patients on Medicare or Medicaid, including simple discounts or rebates, strangely enough). In addition, the vast majority of respondents (84 per cent) felt that they would be more likely to stick with their medications if they earned points for doing so (redeemable for rewards of their choice). And curiously, in an effort to drill deeper, we discovered that $20 worth of points was more enticing than a $20 rebate, despite the equal economic value. Why? Here is what I think: when considering the aspects of healthcare best viewed through the consumer lens, it pays to add the “fun factor” that is so often ignored. People like fun — racking up points, redeeming them for rewards, earning status — a lesson learned long ago by consumer marketers outside of medicine. And when $20 worth of value is earned via compliance, it can be more fun to redeem those points for a gift certificate than to receive a simple rebate of equal value, because the $20 not spent will not really be “felt” and will most likely go to paying a utility bill (a good thing, of course, but not exactly fun). The gift certificate represents “luxury over utility”, or a gift. So, earning statin points is probably pretty similar, from a behavioural psychology standpoint, to earning Marriott points, despite the enormous complexities of the adherence problem and of healthcare at large. But what’s infinitely better about the statin points is that you’re not simply earning a reward in exchange for loyalty, you’re also earning prevention of a heart attack or a stroke. That’s not just good business. That’s good healthcare. 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. In addition to her scientific publications, Katrina is the author of Another Day in the Frontal Lobe: A Brain Surgeon Exposes Life on the Inside, published by Random House and reviewed by The New York Times, The Los Angeles Times, and O Magazine (author website: She enjoys conveying medical concepts to the public and has appeared on CNN, Fox, and MSNBC as a commentator on a variety of medical issues. She is also co-inventor of a brain stimulation device designed to enhance recovery after stroke. 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 1 - Issue 2

Regulatory & Market Place

Emerging Issues and Existing Obstacles to Providing Access to Medicines in Developing Countries The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being, without distinction of race, religion, political belief, economic or social condition (Preamble to the WHO Constitution, April 1948). Synopsis: Accessibility, Availability, Affordability and Acceptability of treatment are considered to be the most important issues for a successful therapy outcome. Each of these four issues can have a specific impact on patient compliance. Limitations in or lack of one or all of the above are considered to have a major impact on patients’ health, not only in developing countries. In the following we will try to identify the underlying causes, their impact on treatment outcome, and the challenges in addressing these issues. Background Access to best available diagnostics and affordable medicine, as well as treatment compliance are among the most important factors to successfully treat any kind of disease. Although considered common knowledge, this is particularly true when we look at the current situation of poor patients, not only in developing countries. From numerous studies and observations by governmental and non-governmental organisations (e.g. WHO, UN, IAEA, UICC and others) aiming to identify the most important and critical obstacles to treatment access and /or patient adherence, we understand that there is no easy solution available short term. One reason certainly is that there is no ‘one-fits-all’ model available that could be applied anywhere, any time. Although much has already been achieved over the last decades, there still remain a number of challenges which most of the organisations and people engaged in increasing access to healthcare in developing countries seem to agree upon. Situation Analyses Access to essential medicine is considered a human right (Preamble to the WHO Constitution, 1948; UN Declaration of Human Rights, 1948). People in the developed world usually take this for granted. But each year millions of people still die due to preventable and treatable diseases such as HIV/Aids, malaria or tuberculosis worldwide because they lack access to affordable healthcare / universal health coverage and (lifesaving) medicines. In Latin America only 35 per cent of the population is covered, 10 per cent in Asia and less than 8 per cent in Africa1. Even in the US in 2009 on average 16.7 % of the population (> 50 million people) were without any insurance, up from 43 million in 20082. Adding the number of underinsured people 22 Journal For Patient Compliance Strategies to enhance Health Outcomes

(those with some kind of health insurance), estimated at > 30% in 2008, more than 50% of all Americans have no or inadequate protection and have to deal with increasing outof-pocket expenses that may lead to personal bankruptcy due to medical debt3. While many people still believe that non-communicable diseases (NCDs, e.g. cancer, cardiovascular or respiratory disease, diabetes) mostly affect high-income countries, the truth is that poor people are much more likely than the wealthy to develop chronic diseases, and are more likely to die as a result. NCDs derive from preventable causes such as tobacco use, unhealthy diet, physical inactivity and alcohol consumption, and are closely related to lifestyle changes. Low- and middleincome countries - whose health budgets are already stretched by other health and development priorities - today also face increasingly difficult choices on how to best allocate their limited resources to fight the rising incidence of chronic diseases, especially in urban settings, while continuing to deal with the problems of infectious diseases. According to the WHO about 60% (35 out of 58 million worldwide) of all deaths are directly related to NCDs; 80% thereof (nearly four out of five chronic disease deaths) occur in low- and middle-income countries4. The World Economic Forum (WEF) has already identified NCDs as the second most severe threat to the global economy as most of these deaths occur in younger people, thus adding to the already negative impact of HIV / Aids on productivity, the economy, and overall national development of these countries5. However, many governments still do not view NCDs as a priority yet; patient awareness and early detection is poor or completely lacking; patient access to care is limited. Medicines to treat chronic diseases, if available, need to be taken continuously to effectively control the underlying condition. Without a comprehensive reimbursement system, or at least access to essential and affordable medicines, this can cause substantial financial burden to patients directly, and often may push individuals and households (even in middle- and high-income countries) into poverty6. Barriers to Accessing Treatment Availability, Accessibility, Affordability and Acceptability are the four most important parameters influencing access to adequate /good quality care, be it basic or highly sophisticated. Each of these parameters also plays a crucial role in attaining the level of compliance needed for a positive treatment outcome. It is relatively easy to understand why immediate and unlimited access to treatment in combination with good patient compliance are important in the case of acute Volume 1 - Issue 2

Regulatory & Market Place medical needs such as treating infectious diseases and HIV / Aids. This becomes, however, more complex when we look at the increasing incidence of NCDs. Many people in communities around the world, especially in underdeveloped and developing countries, increasingly suffer from chronic or neglected diseases - illnesses that could easily be prevented, controlled or eradicated, but often remain untreated due to limited access to (life-saving) medicines and treatment. In the following we will take a closer look at the impact that each single factor may have on access, compliance and outcome, define the challenges, and identify possible solutions Table 1: Access Criteria Accessibility physically reach a health center or outlet Availability obtain adequate medicine at the place of service Affordability cost to the individual including transport, user fees, bribes and loss of income Acceptability treatment perceived as adequate, safe and effectice both by prescriber and patient (Seiter, A: A Practical Approach to Pharmaceutical Policy, World Bank Publ, 2010)

Challenges: Provide access to healthcare specialists for patients in rural or remote areas. Main obstacles are distance, poor transportation options and the cost of transportation itself • Worldwide, people living in rural and remote areas often have problems to access speciality medical care in a timely manner. According to the WHO 70% of people in sub-Saharan Africa live in rural areas, while 90% of their healthcare facilities are in urban areas7. • There is rarely more than one specialised and adequately equipped centre per country. • Outside the major cities only limited services are offered due to lack of adequately equipped hospitals and diagnostic facilities, poorly developed technical infrastructure, insufficient number of pharmacies, nurses or midwives. Solutions: Setting up decentralised health provider networks for local cooperation: • Use of innovative technology may facilitate some aspects of medical practice even when patient and healthcare provider are geographically separated (e.g. electronic transfer of patient records, images etc.) via (mobile) phone, SMS/MMS, e-mail etc. • This may facilitate patient access to speciality treatment; initial diagnosis & treatment could be done at specialist facilities, while follow-up and therapy control would be handled by a local health provider guided via SMS/MMS. Patients would save time and cost for travel, while being able to stay close to family and friends. Accessibility Defined as adequate treatment available at a health outlet at the time of visit.

Table 2: Challenges in Sub-saharan Africa •H  uman resource constraints may hinder management of high-quality care •D  iagnostic capacity esp in cytogenetics and immunohistochemistry is relatively underdeveloped in most African countries •C  lose collaboration among countries in sharing expertise and knowledge needed to provide high quality of healthcare • Government support is key in facilitating the private sector to contribute to healthcare in the spirit of partnership •P  ublic-Private Partnership models are crucial in aiding underprivileged societies to access good quality health care services •P  oor communication infrastructure may hinder the running of such a program • L ocal ownership and connectivity is important •S  ustained funding is needed to ensure that the required education and training programmes can be established Challenges: Poor stock & distribution management at health centres • may result in unreliable supply, unpredictable lead times for delivery and non-availability of essential medicines at the time of visit, Poor information systems, lack of well trained and equipped administration •m  ay result in delayed or faulty paperwork needed to order, deliver and distribute in time; facilities may lack the funds to pay import duties and taxes (and sometimes also bribes) to get even donated drug out of customs. Lack of adequately equipped laboratories and well trained personnel •often results in poor / substandard drug quality, posing a risk for patients. Lack of adequate quality control and regulatory guidelines to identify and prevent local manufacturing / import of substandard or even counterfeit drug. Solutions: Linking and sharing of all kind of medical resources: •A  nalyse, design and implement easy-to-handle drug tracking systems, and document exchange via (mobile) phone (or, where available, the internet - see Accessibility Solutions above). Distance learning and continuing education: Enable online access to product information, e-learning providers (e.g. AfrOX), CME options, scientific communities in general, expert opinions etc. •P  romote local research and clinical trial collaborations with global institutions and / or manufacturers. Affordability Defined as cost of treatment in relation to available overall and / or individual income. •O  n a country level this may have various causes: e.g. lack of local manufacturing and R&D, patent protection, manufacturer’s intellectual property rights, high import taxes and duties, risk of corruption and fraud. • For the individual patient this not only refers to the cost of the drug itself, but also to payments for any kind of Journal For Patient Compliance Strategies to enhance Health Outcomes 23

Regulatory & Market Place diagnostics and laboratory work, transport, user fees (and bribes?), in addition to the loss of income due to absence from work. Challenges: Governments don’t view NCDs such as cancer as a priority yet; • awareness and knowledge about positive effects of early detection on disease development (and resulting treatment cost) is still low or completely lacking. • Limited or complete lack of comprehensive reimbursement systems / health insurance coverage results in a high percentage of out-of-pocket payments by the patient According to the WHO approx 80% of all drug in developing countries has to be purchased at local pharmacies and paid out-of-pocket8. Solutions: Create awareness at government level about the impact of NCDs on a country’s economy, and foster responsibilities. • Help empower patients: support peer-to-peer and patient advocacy networks through (early) education; • Help design and implement country-specific access models in close cooperation with local governments, taking into account their specific financial limitations. • Support local fight against corruption and fraud. Acceptability Defined as a treatment that is perceived as adequate and effective by both physician and patient. Challenges: Physicians have to make sure the best available drug is prescribed, they have to tell their patient how to best take it (e.g. with or without food, mornings or evenings), what possible side-effects may occur, what kind of interactions or contraindications with other drugs and food could happen (e.g. less effect when taken with milk). Pharmacists have to make sure the patient receives the correct medication and maybe again explain correct intake to be effective. In some cases additional information about proper storage to prevent degradation of the active ingredient (e.g. for temperature-sensitive drug) may be needed. Lack of adequate information about compliance with a specific treatment plan may result in taking less than the prescribed dosage. Treatment could be interrupted if the patient feels better or symptoms are gone, and started again at new onset of symptons, thus ultimately causing drug resistance. Even more important is a patients’ adherence when continuous drug intake is necessary to control chronic disease, especially when symptoms are absent. Addressing this need is often limited by human resources: insufficient well trained healthcare workers - physicians, pharmacists, nurses, midwives - and poor information (language, lack of knowledge, low literacy level). Unknown side-effects may frighten patients (e.g. urine turns red) and cause the patient to stop treatment. Limited patient monitoring options and lack of (emotional) 24 Journal For Patient Compliance Strategies to enhance Health Outcomes

support can cause isolation and stigmatisation. •C  ultural and faith-based aspects of care, such as observing religious requirements (e.g. Ramadan), interference of traditional healers, and adherence to traditional medicine, may further impact compliance if treatment is not well explained and understood by patients and their immediate environment (family, friends, community etc). Solutions: Translate treatment information to local language, where feasible: •u  se pictures if low literacy levels prevail • train community members (nurses, midwives) to support patients and their families • empower patients through patient advocacy groups, support peer-to-peer education (see above) • increase awareness through early education and information. Public-Private Partnerships: Close collaboration and knowledge-sharing between all stakeholders - local governments, international organisations and NGOs, drug manufacturers and the scientific community across nations – is crucial in implementing sustainable healthcare systems in developing countries9,10. Product donations and philanthropic activities can have a meaningful impact on global access to medicine as welldesigned donation programmes can substitute or complement local efforts to provide care to eligible patients. A number of existing programmes are already successfully addressing these needs11. Strengthening Local Governments: through monetary assistance, knowledge transfer, support in developing and setting up sustainable reimbursement and insurance systems, infrastructure support (increase local R&D capacity ,improve drug manufacturing quality and distribution management, secure storage, increase counterfeit / fraud prevention, implement and increase quality control). Strengthening Medical Resources: increase availability of well trained primary and specialist care physicians, nurses, pharmacists, laboratory staff; well equipped hospitals, day care centres and laboratories; mobile health outlets along the most frequented routes in areas of high nomadic activity. Volume 1 - Issue 2

Regulatory & Market Place Table 4: Public Private Partnership Projects (excerpt) • NovoNordisk: cost containment pilot program with local distributors in Tanzania • Novartis: “SMS for Life” Malaria Initiative, uses mobile phones for pharmacies & distributors to prevent out-of-stock situations • Novartis / Sandoz: single-drug donation programs for leprosy and CML (GIPAP) • GSK: biggest pipeline of drugs for neglected diseases & most comprehensive vaccine development programme; reinvests 20% of profits into health infrastructure projects in least-developed countries: partners with NGOs to support healthcare workers in Least Developed Countries (e.g. AMREF, CARE, Save the Children, GAVI Alliance) • Gilead: partners with MedicinesPatentPool to access HIV drug library

• Pfizer: partners with DNDi to identify NTD drugs and support for various tropical illnesses • GSK & Pfizer: launched ViiV Healthcare, a company dedicated to HIV not-for-profit pricing & voluntary licensing; supports international HIV Collaborative Research Trials (CRTs) in resource-poor settings; partners with Elizabeth Glaser Pediatric Aids Foundation, amfAR, The Foundation for Aids Research, International HIV/ AIDS Alliance • Bayer: 5year single drug donation program to WHO for sleeping sickness • J&J: R&D program to develop heat-stable vaccine • PATH / WHO: Meningitis- Vaccine Project financed through a grant from Gates Foundation

Strengthening Knowledge Transfer through Education Initiatives and Funding: facilitate scientific and operational collaboration between more and less experienced and equipped institutions; (visiting physicians programmes, fellowships); use information technology (e-learning, online congress coverage, telemedicine); provide educational / training material and programmes on early detection, prevention and treatment. Strengthening Patient Adherence: through continuous education, use of technology (mobile phones, SMS, volunteer telephone trees, local radio stations, internet), phone check-in through hospitals or local volunteers, peer support, advocacy /patient groups; family involvement; easy to understand package inserts and disease information, even for low-literacy, (native language, pictures). What’s Already Happening Financial and Intellectual Support: • develop and establish comprehensive health systems, fund training and state-of-the art equipment: (World Bank, IMF, USAID, EU, IAEA etc). Lift trade-related barriers: • enhance knowledge transfer to enable local quality drug manufacturing; • establish regulatory and quality control, laboratory expertise, enable not-for-profit drug development through patent-sharing (e.g. The Global Fund PatentPool, DNDi). Drug / Treatment Access programmes: • indirect distribution (single buyer, e.g. WHO) through government distribution channels, • direct-to-patient donations through cooperation between local governments, international organisations, NGOs, private aid groups, manufacturers. Conclusion: Improving access and compliance is a combination of money and ideas. Money has a big impact, but only if countries have

good economic institutions and policies. Innovative thinking and /or knowledge creation is critical for helping countries reform and for helping communities ef fectively provide public services: education, health, water supply, and others12. The health and standard of living of all people is a shared responsibility of governments, healthcare institutions, international organisations and the private sector. Terms: IAEA = International Atomic Eneregy Agency, UICC = I nternational Union against Cancer / Union International contre le Cancer) DNDi = Drugs for Neglected Diseases IMF = International Monetary Fund, EU = European Union, USAID = United States Agency for International Development AfrOX = Africa Oxford Cancer Foundation, References 1. Office of the United Nations for Human Rights, 2010 2.US Census Bureau; 2010 Current Population Survey (CPS) Annual Social and Economic Supplement (ASEC), Sept 2010 3.Himmelstein, DU. et al.; Medical Bankruptcy in the United States, 2007, Am J Med, 2009 PBS reports that in 2008 44 million Americans are uninsured, and another 38 million are underinsured, which means they can face thousands of dollars in medical bills if they become ill 4.World Health Organization, WHO: Global status report on non-communicable diseases 2010, 2011 5. World Economic Forum, WEF, Calls for cooperation to fight chronic disease, Annual Meeting 2011 6. Himmelstein, DU et al.; ibid 7. WHO; ibid 8. WHO, ibid 9. Global Health Council, Annual Congress 2008 10. Kanavos P, et al;: Globalization and Health 2009, 5:19; Benefits of global partnerships to facilitate access to medicines in developing countries: a multi-country analysis of patients and patient outcomes in GIPAP 11. Table 3 - The Access to Medicine Index Report 2010, 12. Seiter, A; A Practical Approach to Pharmaceutical Policy, Directions in Development, World Bank Publ, 2010 Walburga A Marder holds a degree in Life Sciences from Albert-Ludwigs-Universität Freiburg /Brg (Germany). She spent most of her professional career in pharmaceutical Marketing, Business Development & Licensing and Communications, with a strong focus on Cancer advocacy. Between 2005 and 2011 she worked as a Regional Coordinator Patient Access for Eastern Europe, Middle East and Africa for Novartis Pharma AG. Email:

Journal For Patient Compliance Strategies to enhance Health Outcomes 25

Regulatory & Market Place

Using Prevalent Technology to Monitor and Improve Adherence Improve Adherence: A simple, patient-friendly solution based on smartphones could play a central role in improving adherence both in trials and in commercial use, argue Steven Carden and David Russell of PA Consulting Group and Graham Howieson of GH Consulting It has been estimated that around 50% of patients do not take their treatments as prescribed; even when drugs are free at the point of delivery, the figure can be close to 40%. In the US alone, poor adherence costs around $100bn per annum and causes almost 90,000 premature deaths. Adherence is a problem both in trials and in commercial use. Both need attention, but there is a different business model and benefits case for each. The Value of Adherence Monitoring for Drugs in Commercial Use In commercial use, improving adherence is already a key goal of manufacturers, healthcare specialists and policy-makers alike. Assuming the benefits of a treatment outweigh the side-effects, everyone wins if patients take their treatment as prescribed, including the patients themselves. Adherence is becoming more important still as a result of recent trends such as personalised medicine, patient-centric healthcare and telehealth. These trends ask patients to take ownership of their own treatment, at a time when treatment is tending to become more complicated. And, as a treatment regime becomes more complicated, so the adherence to that regime is likely to fall. Another factor that will increase the emphasis on adherence in the commercial arena is the pharmaceutical industry’s impending move towards more payment by results. Payers and regulators will demand a better standard of evidence from trials, and so it may become necessary to measure and report, rather than simply estimate, non-adherence. Adherence by patients will be critical to achieving the desired results and hence the payments. The converse of this point is that if the treatment is not working, or is having adverse effects, the manufacturer and clinician need to know as soon as possible. This knowledge allows them to manage costs, to improve the patient’s condition by intervening, and, longer-term, to comply with pharmacovigilance requirements. Collecting feedback directly from patients on their physical wellbeing and state of mind is a rapid way of getting this knowledge, and can conveniently be done while monitoring adherence. Patient feedback is also valuable in the context of personalised medicine. Patients often adapt their own treatment. For example, a “one size fits all” regime of two pills a day may have been prescribed, but the patients may find they feel better taking half a tablet four times a day. Knowing how patients are using and tailoring their own medication helps manufacturers and clinicians to develop personalised treatments. 26 Journal For Patient Compliance Strategies to enhance Health Outcomes

Adherence in Clinical Trials Let us now turn to the somewhat more contentious area of adherence in clinical trials. Here, the business case for monitoring and improving adherence is not quite so clear, as a level of non-adherence is typically built into the trial and statistical models. In addition, the current way of doing trials is predictable so it is tempting simply to stick with it. However, there is no getting round the fact that lack of adherence in a trial leads to inconsistent and inaccurate data, which can extend the trial, increase costs, lead to inappropriate decisions and put participants at risk (for example, if they take too much medication). Therefore, investing up-front in a better methodology would have the long-term benefits of improving the quality of, and the return on investment from, the trials. Monitoring adherence would make it possible, for example, to remove non-compliant participants from trials earlier on. This would make it possible to obtain more robust results with the same sample size. Systematically monitoring and improving adherence would be much more cost-effective than the current approach of simply factoring in an assumed level of non-adherence. Because clinical trials are so expensive – costing up to $800m per candidate according to one estimate – even a small improvement can produce large cost benefits. Such considerations are increasingly important since factors such as the lack of new blockbuster drugs and increasing priceconsciousness on the part of payers are putting downward pressure on costs. A more scientific, and proactive, approach to adherence would also make the results more reliable because the statistical significance of results will become more focused – an increasingly important consideration as authorities such as those in Germany raise the bar for the quality of evidence required for reimbursement. Technology’s Role in Improving Adherence Although some commentators consider that adherence is mainly a matter of psychology, we would contend that technology has an important part to play. What is that part? Experience shows that a third of patients adhere pretty well, a third will resist adherence and a third generally want to adhere but struggle to do it consistently. Any attempt to improve adherence should start by considering what can be done to support this last third, for whom the spirit is willing but day-to-day life intervenes. The aim should be to lower the barriers that prevent adherence and to prompt the patient to follow the prescribed treatment. To do so we would argue that a combination of three things is needed:1 education, to make it easier for patients to understand what they are expected to do;2 technology, to prompt, support, and guide the patient to the right place; and3 monitoring, to provide behind-the-scenes support to enable early intervention.

Volume 1 - Issue 2

Company profile

Vitaphone: thÊ telemedicine company Vitaphone was founded in 1999 with the aim of developing technologies to transfer bio signals and biochemical parameters with modern communication tools, and integrate these in innovative service concepts.Vitaphone technologies make possible the collection, transfer and evaluation of medical data anywhere and anytime. The PICO system, a development of Vitaphone the Netherlands, is much more than just a device. It is a Medication Adherent Support System (MASS), a system that guides patients in the correct, proper and appropriate use of medicines. The heart of the system is the PICO, which works in combination with the PICO-cartridge that contains the appropriate medicines prepackaged per intake moment in pouches on a roll. Each individual pouch can be identied by its unique barcode which can be read by the PICO. The PICO is at the patients location (home or elsewhere), and communicates via GSM/GPRS network with the corresponding PICO service, which is essential in improving the adherence to medication. Using the barcode on the individual medication pouch, the PICO MASS tracks if the medication has been taken out of the PICO. If the patient forgets to take his medications, this service reminds the patient and/or alerts a caregiver, thus reducing medication errors to an absolute minimum. After inserting the PICO-cartridge into the PICO, the first thing to happen is a verification if the correct roll is placed in the PICO. The PICO communicates with the patient through its display and by means of sound and light signals. The PICO indicates when the next medication pouch (1 or 2) needs to be taken out, and also the need to exchange the medication roll for a new one is shown. Furthermore, in a weekly overview the patient can track his adherence. Thus, the patient is strongly stimulated to be adherent. The webbased application provides statistics on how the user has taken its medicine, and gives a good inside of the adherence. For supporting Clinical Trials and Clinical research we deliver the GSM/GPRS based solution throughout Europa and the US and Canada including your medication in pre-packed pouches. More on Vitaphone Telemedicine For over 10 years,Vitaphone has been supporting healthcare professionals worldwide with diagnostics, treatment, patient and disease management. The focus is on functional diagnostics in the field of cardiology. We offer a range of telecardiology products and services to Clinics and Hospitals, Clinical Research Organizations, Diagnostic Centers, and Cardiac Device Manufacturers. Our ISO certified Telemedical Service Centers, located in Germany, US and China can offer 24 hour services around the globe. A specialized team of internists, cardiologists and qualified medical assistants are on call 24/7. In cooperation with local partners we develop telemedical supported patient monitoring solutions within the frame of structured programs of chronic patients with CHF, COPD, diabetes. Contact details: Vitaphone The Netherlands BV Ellen Pankhurststraat 15a 5036 MD Tilburg, The Netherlands Tel: 0031 13 4625630 E-Mail: Contact: Erwin van der Star, CCO

Regulatory & Market Place Limitations of Current Solutions There are various potential technical solutions on the market, but none of them has been widely deployed to date. Those that attempt to monitor, as opposed to simply prompting, adherence tend to be in what we would call the “direct monitoring” category, where feedback is obtained without the patient needing to do anything other than take the treatment. In this category we could include smart packaging and pill dispensers which register when the pill is taken out and transmit data to a central monitoring unit. Also in this category are smart pills such as the Proteus “chip on pill”, which contains a circuit that transmits a signal when the pill dissolves in stomach acid. Monitoring concentrations of active substances or markers in serum, urine or breath is another approach. Indirect monitoring relies on some intervention by the patient. Indirect adherence technologies to date tend to be aimed purely at prompting the patient to take the treatment, through reminder devices such as watches and key fobs. There are several problems with direct monitoring technologies. They usually require significant changes to packaging (such as special wallets or plastic cradles). Some are seen as obtrusive, whilst others require significant revalidation. They also tend to be costly to introduce, difficult to scale up and have a long development lead time. The limitation of most indirect devices is that they do not directly monitor or measure adherence, relying instead on second-order measurements. Requirements for a Successful Solution There is unlikely to be a single solution that suits all patients and treatments, and so to optimise adherence a portfolio of solutions is likely to be needed. Nonetheless we would argue that the ideal solution for most patients and treatments is one that: • facilitates real-time monitoring and intervention • has a low barrier to deployment, i.e. does not require revalidation of packaging or medication • engages the patient in the process of monitoring through a two-way dialogue • is non-invasive Why has no one addressed these requirements so far? The most likely explanation is that until recently the right device has not been available. What is needed is a portable device, widely distributed and available off the shelf, that has the capabilities to support an interactive dialogue. It also should be something that patients find easy to use, and even enjoy using. Only now is such a device becoming available, with the advent of affordable, usable smartphones. Outline of a Successful Solution PA Consulting Group and GH Consulting have taken advantage of this development to explore a new approach to monitoring and improving adherence. Dose Recognition (DR) is a noninvasive technology that can work with existing blister packs and packaging formats to provide a patient-friendly method of monitoring and improving adherence. In essence, the system uses an app on a smartphone to send a time-stamped photograph of the packaging (such as a blister pack) to a central repository as evidence that tablets have been removed. 28 Journal For Patient Compliance Strategies to enhance Health Outcomes

Figure 1 summarises the way the system works. First, the app Figure 1: the Dosage Recognition system in action

What the patient does • receive reminder • take tablet • take photo • send photo What the healthcare professional does • upload protocol to the phone • patient training and instruction • manual image processing e.g. where automated image recognition is not possible • specify and review reports • interpretation and intervention

prompts or reminds the patient to take the tablet. The patient takes it, and then photographs the packaging. The image is transmitted to the centre, where either image processing software or a human operator analyses the inputs to check that the treatment is being taken at the right time, in the right way and in the right order. To improve adherence, the system can either generate automatic advice or refer exceptions to healthcare professionals. The data is recorded centrally to build up a picture of individual and collective adherence over time. The same process can build a picture of the patient’s physical and mental state in real time, by prompting for a wellness indicator for example. Pros and Cons of this Approach This approach has benefits in terms of responsiveness, ease of deployment, flexible two-way communication, and general patient-friendliness. It improves responsiveness by providing real-time visibility of patient and trial data, and facilitating early intervention (or, on a trial, patient replacement) in cases of non-adherence. Its ease of deployment lies in the fact that there is no need to revalidate an existing treatment because we are not changing any components which have already been specified. Development and deployment timescales are short. As a lowcomplexity solution it is easy to roll out and also to “tweak” to improve performance. A single solution works across a portfolio of delivery systems (blisters, wallets, bottles, etc). The approach provides flexible two-way communication with the patient, sending SMS reminders and prompts and collecting feedback. Gathering information such as the single unit dose time-stamp is easy. The system can guide patients through complex protocols, prompting them for example to take a pill within a 15-minute window, or to take two red pills followed by a blue pill. Finally, it is patient-friendly in that it uses straightforward devices with which many patients are already familiar. The process is transparent – the patient can see what is going on. As an active participant in the treatment or trial process, the patient feels involved – something that may itself improve Volume 1 - Issue 2

Regulatory & Market Place adherence. The solution does have one or two limitations. It relies on a relatively high-tech device and so would be less suitable for certain patients, such as those with dementia. It requires the patient to take a picture, possibly in public, which may be offputting for some: as acknowledged above, it should be part of a portfolio of solutions to cater for different patients’ needs. A more general limitation is that the system does not monitor the patient’s actual taking of the treatment, just its removal from the pack, and is therefore one step away from actual adherence. In this it is comparable with electronic pill boxes: in both cases, the event measured (taking the picture or opening the box) does not actually prove that the patient has taken the medicine. However, clients tell us this is an acceptable price to pay for avoiding the disadvantages of direct monitoring, such as development and validation effort for the manufacturer, and intrusiveness for the patient. How could this Approach be Progressed? Although the benefits of this approach are potentially greater for treatments in the field than for trials, so are the risks. Rolling a particular approach out to a large patient base would require a major investment. Such investments need to be driven by a solid business case, for which we need hard evidence of a positive effect on adherence. Therefore we envisage that the approach could best be proven on a clinical trial. That way effectiveness and value could be quantified under carefully controlled conditions and on a relatively small scale, before investing in larger-scale deployment. There are also, as discussed above, major benefits to be had on the trial itself, and these will start to be realised almost immediately the trial starts. To summarise, they are: • Real-time visibility of patient and trial data, enabling in-flight adjustments to the trial to improve the chances of success • Early intervention in cases of non-adherence, maximising the value of the trial and minimising the cost • Patient replacement, creating a cadre of patients who can be trusted to support the trial The practicalities would be reasonably straightforward: iPhones or other smartphones could be lent to trial participants, complete with pre-installed trial protocol and software. The system could be run as a paid-for service by companies such as PA Consulting Group and our partner GH Consulting, with us hosting the back office and lending devices directly to patients. Alternatively, we could provide the solution as a product, sold to a contract research organisation (CRO) or manufacturer who would then run the service themselves. To evaluate the efficacy of the approach, there could be a “trial within a trial” with patients divided into matched groups, one with the device and a control group without it. The difference in adherence, and in accuracy of reporting of adherence, between the experimental and control group could then be measured. Once proven on a trial, the approach could confidently be applied to treatments in the field, perhaps with the software available as a downloadable app to run on patients’ own smartphones. One or two practical considerations would have to be resolved: for example, patients would need to opt in to

having their data used in this way. Again there would be a choice of deployment models. Conclusion A pharmaceutical company that takes a lead in the field of adherence monitoring would have a significant advantage in terms of both lower-cost clinical trials and better ROI. A CRO would get differentiation and a value-add service that it can offer to clients to improve their ROI. The DR system is currently under development by PA and GH Consulting and is at the product demonstrator stage. The current demonstrator allows images to be captured on a smartphone and these are sent to an online database. There is no reason why it could not be deployed on a trial in a matter of months. References: 1.Cutler, D.M, and Everett, W., “Thinking Outside the Pillbox — Medication Adherence as a Priority for Health Care Reform”, NEJM, 7 April 2010 2. Fee, R., “The Cost of Clinical Trials”, Drug Discovery & Development magazine: Vol. 10, No. 3, March 2007 Dr Steven Carden leads PA Consulting’s product development service, with 15 years’ experience in developing in-field systems for secondary and primary packaging in the healthcare and consumer products sectors. He is an expert in tackling illicit trade of products, having deployed a number of track and trace and authentication systems, and is currently exploring the intersection of adherence, anti-counterfeiting and pharmacovigilance. Email: Dr David Russell is an applied physicist with particular strengths in new product development within the healthcare and consumer products sectors. Primarily focused on solving the technical roadblocks in the development cycle, David’s expertise is in turning great ideas into commercially viable products. Email: Graham Howieson is an industry veteran and entrepreneur. Since 2000 he has been actively involved, leading the design, development and supply of various clinical trial materials & technology based solutions. Working with international partners and across a global reach he has successfully launched a number of these new concepts into the pharmaceutical marketplace. He continues to focus on the future with a view to improving the patient experience. Email:

Journal For Patient Compliance Strategies to enhance Health Outcomes 29

Behaviour Programmes

Family Ties: Educating and Engaging Caregivers for Retention Success The caregiver, whether family member or friend, is the study participant’s partner in disease management and decisionmaking. He or she is, perhaps, the patient’s most important source of emotional and physi¬cal support — a role which can be both rewarding and demanding. To the study team, the caregiver is a key resource for ensuring the patient attends study visits, is compliant with study procedures and accurately records and reports responses to study medication. In short, the caregiver is fundamental to patient retention and, ultimately, clinical trial success. This is particularly apparent in trials involving children, seniors and individuals who are chronically or terminally ill. Clinical trial sponsors can maintain a competitive edge by developing proactive retention plans that incorporate caregiver components. In addition to studies lasting several months or years, such retention plans have relevance for shorter studies requiring frequent site visits or lengthy appointments. Studies with difficult dosing regimens, invasive procedures, extensive third-party support and unpleasant side-effects associated with the investigational medication also warrant caregiver strategies. As a supplement, adherence programmes offer guidance on proper dosing, staying in the study and attending site visits. Clear, concise communication is key when discussing study requirements with patients and caregivers. By anticipating their questions and addressing them candidly in layman’s language, you can help de-mystify an often intimidating topic. It is essential to detail the potential benefits to the participant and to the future of medical science, and reinforce that participants receive quality care and vigilant monitoring. Below are suggestions on subjects to cover: About the Study… What is the goal of the study? What are the benefits and risks of participation? What makes certain patients good candidates for participation? How long will the study last? About the Investigational Medication… What are the potential benefits of the investigational medication? What are the potential risks and side-effects associated with the investigational medication? Are there foods, drugs or activities that patients should avoid while in the study? About the Study-Related Tests… What kinds of tests will be administered? Do patients have to do anything special to prepare the participant for the tests? Do these tests have any side-effects or risks? What do you expect to learn from these tests? Will patients and caregivers be informed of test results? If yes, how? 30 Journal For Patient Compliance Strategies to enhance Health Outcomes

Cultural Considerations When communicating with study participants, it is essential to consider their cultural perspectives. However, respecting cultural differences goes far beyond simply providing an interpreter during informed consent. The ethnocultural perspective of patients and caregivers may influence their view of doctors and institutional medicine. Understanding their point of reference can help you better address their questions and customise your responses. Of course, knowing the traditions and values of every culture is unreasonable; however, your sensitivity to perceived differences may help strengthen your relationships with your patients and can help foster understanding and promote their quality of life. Below are a few things to consider: •A  sk the caregiver if your patient observes cultural practices that may impact study procedures or the medication schedule. •P  rovide written materials in the patient’s primary language. •A  sk about your patients’ use of alternative and complementary medicines. Some cultures have different expectations and rules about personal space, body language, eye contact, pitch of voice, and hand gestures, so it may be better to take a conservative approach if you’re unsure about preferences. Finally, choose a certified medical interpreter over family members or untrained staff when communicating with patients. A professional will be unbiased and versed in medical terminology. Recommended Strategies Once enrolled in the study, caregiver education and support should be comprehensive and consistent. Maintaining participant interest and compliance in a study can be challenging. It will be important to establish an aggressive retention programme that includes relationship-building strategies, participant recognition and communication tools. Contact your regional monitor for ideas and assistance. Individual programme elements may include: Logistical • Maintain flexible, convenient appointment times. • Mail or email appointment-reminder cards. •O  ffer transportation assistance to ease the logistical and financial burden of attending frequent study visits. Educational •C  ustomise retention training for investigators and study coordinators focused on best practices in caregiver communication and patient retention. •O  ffer caregivers 24-hour coordinator contact information. •P  rovide ongoing education via print, text or online Volume 1 - Issue 2

Behaviour Programmes

communication to keep caregivers informed of study updates, appointments, disease processes and patient care tips. • Develop a study website with a password-protected section for patients and caregivers.

Retention Training * Patient Support Packages * Caregiver Support Packages * Visit Reminder Postcards

Emotional • Set aside five to 10 minutes at the end of each visit for the patient and caregiver to ask questions and discuss issues of concern. • Write to or telephone caregivers between visits. • Send special occasion cards (e.g., birthday and holidays). • Create caregiver kits containing tools for use during patient transport and study visit attendance. • Develop a caregiver recognition programme. • Provide services (e.g., support group referral, reading resources) to help caregivers cope with the rigours of care-taking.

THE RESULTS Figure 1: the Dosage Recognition system in action

Physical • Ensure each participant sees the physician at each visit. • Provide summaries of lab reports or other health status information. • Include additional information about the study drug and safety profile. Case Study: Proactive Alzheimer’s Disease Retention Programme INDICATION: Mild-to-Moderate Alzheimer’s Disease STUDY DETAILS: * Proactive campaign * 12-month retention programme * 70 sites * 930 patients * 12 countries RETENTION CHALLENGES: * Nature of the condition * Study requires caregiver attendance at all office visits * Nausea and digestive issues are known side-effects of the drug DAC’s SOLUTIONS: * Engage the patient and caregiver regularly throughout the study * Provide ongoing education and support to sites and study CRAs * Provide ongoing education and support to patients and caregivers THE CAMPAIGN: * CRA Recruitment and Retention Training * Investigator and Study Coordinator

*A  ttrition rate trended at 10% far below norms of 25-35% attrition * This is a difference of 25% belowthe expected attrition rate of 35% normally associated with the study indication Keep Lines of Communication Open Caregivers bear inordinate demands on their time and emotions but by supporting their efforts to develop coping strategies, you may avoid caregiver exhaustion — a frequent precursor to subject withdrawal. Following are tips for clinicians from the National Family Caregiver Association. •B  e open and forthright. •T  hink about the practicality of the treatments you suggest and consider their effect on the entire family, not just their medical efficacy. •W  hen you prescribe medications, be sure caregivers understand potential side-effects so they know what to expect. • I n non-life-threatening situations, assure caregivers that every decision doesn’t have to be made on the spot. Respect the right of the caregiver and the patient to think things over. •N  ow and then ask the caregiver: How are you? Let them know you understand that illness and disability are a family affair. •B  e accessible — especially when a caregiver is opening his or her heart. Journal For Patient Compliance Strategies to enhance Health Outcomes 31

Behaviour Programmes comparable levels of depressive symptoms. But after one year, 29.8 per cent of caregivers in the enhanced treatment group had symptoms of clinical depression compared with 45.1 per cent of those in the usual care (control) group. Significant differences in the mean number of symptoms were found through the third year of follow-up. The difference between the two groups gradually diminished over a five-year follow-up period. The results of this study indicate that an individualised programme of combined counselling and continuing support is a strong intervention for caregivers. Retention success is a direct result of patient and caregiver satisfaction. Routine surveys can help sites assess performance, identify problems and frame new strategies. Remember, retention programmes need the human touch to be effective and this can only be achieved at the “point of care”. Nothing replaces genuine concern in making study participants feel part of a higher purpose.

• Reach out to the caregiver — literally. A simple touch can mean a great deal. • Be sensitive about where you talk to caregivers about difficult subjects — waiting rooms and corridors are not appropriate. • Always explain as completely as possible all of the legal ramifications of life-saving actions. • Be prepared to point caregivers toward helpful resources. Living with a chronic illness or disability requires more than medicine has to offer. Caregivers donate a great deal of energy to someone else’s needs, and often ignore their own. You should acknowledge that there may be days when the caregiver will feel angry and resentful, guilty and impatient, ashamed and lonely, or fearful of the future. These feelings aren’t wrong or narcissistic — they are normal responses to extreme stress that providing care can cause. Refer the caregiver to resources that can assist during periods of high emotional stress (e.g., books, organisations, web pages and support groups). Families can cope with the demands of caregiving, in part, by educating themselves and reading accounts of others who share their experiences. Short-term intensive counselling in conjunction with readily available support can significantly reduce the long-term risk of depression among caregivers. In one Alzheimer’s study supported by the National Institute on Aging (NIA), the positive impact of these interventions continued for more than three years after the initial counselling sessions ended, and persisted even after patients either passed away or were placed in nursing homes. “This research offers striking evidence that distress and depressive symptoms in family caregivers can be effectively eased and that the benefits can be sustained over a long period of time,” says Sidney Stahl, Ph.D., of the NIA’s Behavioral and Social Research Program. Symptoms of depression were compared over time between two groups. When they began the study, the two groups showed 32 Journal For Patient Compliance Strategies to enhance Health Outcomes

Diana L. Anderson, Ph.D. As president of DAC Patient Recruitment Services, Dr Anderson is an international thought leader in patient recruitment and retention for clinical trials. She is a coveted speaker and author of five industry books, including “Global Issues in Patient Recruitment and Retention,” set for release in 2012. Email: Global Caregiver Resources AARP International Canadian Caregiver Coalition Eurocarers National Alliance for Caregiving National Family Caregivers Association New Zealand Carers Alliance Pan American Health and Education Foundation Taiwan Association of Family Caregivers Sources Alzheimer’s Disease Case Study. DAC Patient Recruitment Services “Improving Doctor/Caregiver Communications.” National Family Caregivers Association. “Enhanced Counseling, Support Interventions Slash Long-term Risk of Depression among AD Caregivers.” National Institute on Aging, May 2004. Volume 1 - Issue 2

Clinical Trials

Effective ePRO Training Increases Patient Compliance and Yields Better Clinical Data Due to the increased demand for greater efficiency in clinical trials by both sponsors and CROs, the author explores this critically important issue from several perspectives. In this article the author reviews the scientific literature to determine if there is a correlation between effective ePRO training and increased patient compliance in clinical trials. There is significant evidence indicating that patient satisfaction is high with ePRO devices1 and that a majority of patients find the devices very easy to use2. In addition, there is both anecdotal and quantitative evidence that patient training on the use of ePRO devices does have a positive impact on overall patient compliance3 and does yield superior clinical data. The author reviews four ePRO device training scenarios that are likely to increase patient compliance and produce better clinical data. The first ePRO training usually occurs at the kick-off meeting, where the ePRO provider is educating the sponsor and/or a CRO. The second ePRO training is typically at an investigator meeting where either the ePRO provider or other sponsor delegate is conducting training for a diverse group of clinical trial professionals including study coordinators and investigators. After this, monitors or CRAs from the sponsor or CRO train investigational site staff with the ePRO device, and then finally the investigational site staff, typically a study coordinator, trains patients directly on the use of the ePRO device to collect the patient-reported data. The ePRO provider is directly involved in the first two training scenarios, and it is here that the use of best practices in training have the most impact. However, it should be noted that the ePRO provider can also directly and indirectly impact the two on-site training scenarios through best practices. During a kick-off meeting, the ePRO provider delivers their initial presentation, which is then often followed by a design meeting. The design meeting is the first in a series of activities, all of which must be executed to extremely high levels of competence and professionalism, in order to achieve the ultimate goal of maximum patient compliance in a clinical trial. During the design meeting the ePRO provider will articulate their assumptions, interpretation of the protocol, deliverables, timelines and other relevant data to the sponsor and/or CRO. In order to facilitate making the most intelligent and effective design decisions, it is critical that the sponsor organisation have an opportunity to gain hands-on experience with functional ePRO devices. The sponsor team must have sufficient time during the meeting to experiment with the devices and learn how the hardware and software operates, what the device can do for them, and recognise the value of its capabilities. It is only through this hands-on experimentation with the ePRO device that the sponsor team can ask questions of the ePRO 34 Journal For Patient Compliance Strategies to enhance Health Outcomes

provider’s technical experts, and gain a high level of comfort with the capabilities that the device will bring to the study. One of the most important outcomes from this experience should be a strong sense of ownership of the ePRO solution by the sponsor team. Top ePRO providers take great care to ensure that their devices have the highest possible degree of usability and this facilitates a sense of ownership. During the investigator meeting, many of the same best practices should be followed. While this is complicated by the sheer amount of information that needs to be disseminated, here too it is critical that the site monitors, study coordinators and even investigators are engaged with the actual devices. In this case, the outcome of the hands-on experimentation with the ePRO devices should ideally go beyond ownership. The site monitors, site coordinators and the ePRO provider must develop a sense of partnership through their collaborative hands-on training with the ePRO devices. Here the desired outcome is a high level of confidence and enthusiasm on the part of the site monitors and study coordinators. This is extremely important because that confidence and enthusiasm will be transferred directly to the site staff and ultimately to the patients. According to Jordan E. Lateiner, MS, MBA, Assistant Volume 1 - Issue 2

Clinical Trials

Director, Clinical Development at Forest Laboratories, “It’s very important that the training is hands-on. Each site monitor and site coordinator should have the opportunity to individually experiment with the device, complete a questionnaire and learn how to transmit data. Additionally, there must be an opportunity to ask questions of the ePRO provider. The device should be treated like an advanced modality where hands-on training is a requirement.” When asked how training at this level impacts patient compliance with the use of an ePRO device, Mr Lateiner responded, “If the study coordinator is confident in explaining how the device is used and why it is important, that will be communicated right down to the patient. It is training but it is also messaging. Therefore, if you train your study coordinators extremely well at the investigator’s meeting and they understand why you are collecting the data, how to collect the data and how to troubleshoot any issues, then the patient will have the same feeling as to why this is important, how do I use this device, and what do I do if there is a problem.” Thus it appears that highly effective, formal training of the sponsor, CRO and their staff does have a direct impact on patient compliance with the use of ePRO devices. However, sophisticated ePRO providers take additional steps to increase

patient compliance. Each device is pre-loaded with training software specifically designed for the patient. Training materials are also included to assist the patient once they have left the site. This training software allows the patient to see how the device works, how to enter data and how to log in, among other features specific to that study. The patient can use the training software until they have achieved a level of comfort. At the end of the training walk-through the software asks the patient to respond if they are now comfortable with using the device. Once the patient answers yes, the training software logs the date and time and activates the study software. Mr Lateiner adds “It is extremely important that the site coordinator monitors patient compliance using the ePRO provider’s web portal. It is very important to sponsors to ensure that the site coordinators understand the vendor portal and are diligent in ensuring timely patient completion of questionnaires. The elapsed time between study visits is often a matter of months and therefore careful oversight of ePRO device usage is paramount.” In conclusion there does appear to be both empirical evidence as noted in the opening paragraph, and strong anecdotal evidence that effective ePRO training increases patient compliance and, by definition, produces superior clinical data. This is of utmost importance for sponsors and CROs as they look to increase efficiency, lower overall costs and gain rapid insight into clinical trial data and patientreported outcomes. It is evident that investing the time and effort to conduct effective ePRO training does yield better patient compliance and better clinical data. References 1. McLellan, C. B., Schatz, J. C., Use of Handheld Wireless Technology for a Home-based Sickle Cell Pain Management Protocol. J. Pediatr. Psychol. 34 (5) 564-573. (2009) 2. Finkelstein, J., Cabrera, M., Internet-Based Home Asthma Telemonitoring. Chest. 117. 148-155 (2000) 3. Cohen, D., Leviton, L., Online Diaries for Qualitative Evaluation, Gaining Real Time Insights. American Journal of Evaluation 27 (2) 163-184 (2006) Colin Cleary is a Program Manager with CRF Health responsible for operations and account management of Sponsor relationships. Prior to CRF Health, Mr. Cleary managed an Asthma Research and Education program at Thomas Jefferson Medical College. Mr. Cleary holds a Masters in Public Health from Dartmouth Medical School. Email: Journal For Patient Compliance Strategies to enhance Health Outcomes 35

Clinical Trials

Patient-Centred Clinical Trials A short while ago, I was reading a book entitled ‘WWGD?’ (‘What Would Google do?’), an interesting book on Google’s business philosophy. The authors proposed to reverse the traditional product development process. In the past, it used to be the ‘Product Development’ department who created new products based on what they felt consumers would be in need for. The authors argued that product development should start with analysing Google search trends to find out what type of products ‘consumers are searching for’. As they argued: ‘what is the purpose of developing a product if consumers are not searching for it [in Google]?’ Let’s find out if this concept can be translated into pharma, and if and how patients should impact R&D. Patient-Centred Product Development I will start off with an example of how patients could impact product development. It is based on a study by the Dutch Burns Foundation. Based on a survey among the treating physicians, the top 10 of aspects to study are related to cosmetic surgery or treating burned skin. Which makes sense, as that seems to be the most obvious problem patients are facing. However, for the actual patients, itching was felt to be one of the major problems. In other words, researchers were looking for answers to problems which were felt less relevant to patients, and problems which were felt as important by the patients were not investigated. This is where ‘patient-centred clinical trials’ should start, with developing treatments which ‘meet the consumer’s needs’. It is interesting, to say the least, to see what is happening in the area of rare diseases. This is an excellent example of patient-driven research, and also an area where ‘patient meets pharma’. It is not uncommon to see patient organisations active in fundraising for research, and being actively involved in directing and organising clinical research, often in close cooperation with pharma or biotech. Needless to say, this model will reduce the chance of a mismatch between ‘product development’ and ‘consumer requirements’. Will this close interaction between patient and pharma always work? No, certainly not. Pharma is, and should be, a commercial industry with a different motivation than what drives a patient. However, Google is also a commerciallydriven company. And by placing the customer in a central position in its business process, it has grown in 13 years to a size unmatched by even the biggest pharma companies. How can Pharma Engage with Consumers on Product Development? Social media and web 2.0 can provide excellent tools for this interaction. Looking again outside of pharma, large consumerdriven companies have embraced tools like idea management to interact and engage with consumers. Sure, it is easier for a company like Starbucks to listen to its consumers, as everybody has something to say about coffee. Different from, say, chemotherapy to treat multiple myeloma; but even with this type of treatment, patients will be able to better balance 36 Journal For Patient Compliance Strategies to enhance Health Outcomes

the side-effects against the treatment effects. Most oncology trials are focusing on survival rates, the traditional outcome measurement. But what is the purpose of spending large sums of money on getting approval for a drug which most patients will refuse because they have a different angle on quality of life than pharma has? Therefore, both pharma and consumers (patients) can benefit from joint discussions on trial objectives. Patient-Centred Clinical Trials One of the advantages of engaging patients in an early phase of organising a new trial, is that it becomes a logical next step to involve patients, most probably patient organisations, in the practical setup of a study. Most clinical trials are the result of business negotiations between sponsor and clinical sites. This guarantees that Volume 1 - Issue 2

Clinical Trials

business objectives of both pharma and investigator are met. The missing piece of the pie is in the patient’s objectives. Patient objectives are assumed to be met by the fact that a new treatment is offered. However, as soon as the burden of trial participation outweighs the actual outcome of the treatment, patients drop out, resulting in loss of ‘investment’ and usually resulting in extended trial durations. How can this be avoided? ‘Information’ and ‘communication’ are the key words. Open communication on the ‘business objectives’ of each stakeholder, including patients, will result in a better understanding of why patients are participating, and how participation and retention can be enhanced. Are patients participating because of financial payment? If so, does the financial compensation properly balance the actual ‘investment’ of the patient, like extra travel to a hospital? If not, would it require either more payment, or a different visit schedule, or can visits be scheduled closer to the patient’s home? Or is the major motive of patients related to their desire to ‘advance medicine’? If so, is there a feedback loop at the end of the study which will inform patients on study results (even if the results are not positive)? Or are patients hoping that entering a trial will give them access to a new treatment which will cure their disease? If so, have they been informed that chances of a new treatment being able to cure their disease are usually slim? Failure to understand, and take into account, the objectives of patients to participate in clinical research, can only result in loss of motivation, and finally in patients dropping out of studies. How can Pharma Engage with Trial Subjects? We all know that pharma is a heavily-regulated environment, therefore direct engagement with trial subjects is usually a no-go. However, this still leaves many options open to engage in a direct discussion between pharma and patient (organisations). Stepping again outside of pharma, there is a lot to learn from other industries. It is impressive to see how web 2.0 tools can enhance the interaction between companies and consumers. In 2008 Starbucks launched MyStarbucksIdea. com and invited its customers to tell the company what it should do. One client suggested to have ice-cubicles made of coffee, in order for the coffee not to be diluted when the ice melted. An overwhelming 7600 other clients supported this idea. Translated into pharma, companies could have an online forum dedicated to a new study and open access to an invited set of patient organisations, or other stakeholders, and have them comment on study details. Similar use of these social media tools can be made during a trial or even post-trial. A perfect example is UCB Pharma, which has teamed together with patient community PatientsLikeMe. UCB is going to use the web 2.0 tools of PatientsLikeMe to gather data about epileptics, including whether or not they are currently on a UCB treatment. The advantage for UCB is

that they get longitudinal data on thousands of patients and will be able to understand the effect of different interventions on the quality of life of patients. The benefit for patients is that pharma will be able to tap into their day-to-day problems and gain a much more detailed insight into the effect of their medication. And the idea of using a pharmacovigilance person to monitor adverse events reporting (as used in the epilepsy community), could easily be transferred into actual clinical trials as well. This could solve one of the major concerns of pharma to engage in social media: adverse event reporting. If you have an independent person monitoring a patient forum, and acting on and reporting any possible adverse events, this will meet current regulations. It is equally important to keep in mind that using social media can be as ‘open’ or ‘closed’ as needed. Most people seem to associate social media with more or less open community tools like Facebook. However, social media is only a tool which can be used in an open community, but just as well in a closed community. As an illustration, a social media tool allowing people to communicate with each other can be used to allow each stakeholder in a trial to discuss with any other stakeholder, or it could be used to allow online communication only within each ‘community’ of each individual investigator with his/her own patients. In fact, this last example is more or less what Pfizer is doing in its first-of-its-kind 100% e-trial. In this study, trial participants are able to communicate online with the researchers. Summary and Conclusion In conclusion, enhancing patient engagement in clinical research should not be limited to patients participating in clinical trials. It is a process of interaction between pharma and patients which starts in the early phase of study development and extends throughout the ‘lifetime’ of a new drug or treatment. We have used examples from inside and outside pharma to illustrate the potential of using social media tools to interact (‘engage’) with consumers/patients. Needless to say, this transition towards greater patient engagement will undoubtedly result in enhanced patient motivation and compliance in clinical trials. It illustrates the ongoing trend for patients to become more active in their healthcare decisions. Sjouke Huisman, MSc. is co-founder of Clinical Study-Portal. Clinical StudyPortal, founded in 2010, is providing a generic solution to organisations involved in clinical research to share information and engage with selected groups of stakeholders. Sjouke has been working in Pharmaceutical industry and clinical research for over 20 years. He has mostly been involved in projects related to Quality of Life studies, data collection and EDC. Email: Journal For Patient Compliance Strategies to enhance Health Outcomes 37


Learning from Social Media about the Patient Journey and Adherence People with Alzheimer’s disease and their care partners are using social media to share their experiences with Alzheimer’s disease and treatment. This unfiltered exchange of information offers access to raw insights that can drive innovative solutions to overcome the challenges of adherence and improve outcomes for patients and healthcare providers (HCPs). Marketers increasingly recognise the advantages of listening to what patients are saying in social media. “E-patients” have become an important source of unguided input that can help brands better understand the challenges to adherence. It is important, however, to recognise the limitations of social media mining, including bias on the part of overly enthusiastic commenters, or the highly emotional or irrelevant comments of ranters and ravers. To help avoid these limitations, traditional market research techniques still have a role in ensuring that a representative sample is obtained. This article examines the importance of social media as

38 Journal For Patient Compliance Strategies to enhance Health Outcomes

a source of insights about patient behaviour that may not be captured elsewhere. These findings were presented at theExLDigital Pharma East conference in October 2010. Using Social Media to Understand and Plot the Patient Treatment Journey Given the volume and diversity of social media conversations, marketers need a blueprint to organise and distill key findings and implications. HealthEd’s health educator and strategy team analysed 2000 comments from 20 web portals in our search for common and actionable insights related to adherence in the Azheimer’s disease patient journey. We then organised those comments by theme and partnered with our creative team to develop a visual representation of the Alzheimer’s journey. The resulting illustration depicts key barriers, drivers, and educational opportunities — and includes an unexpected barrier in the journey. Visualising the Alzheimer’s Patient Journey

Volume 1 - Issue 2

Therapeutic Social Media Mining Confirms Barriers in the Alzheimer’s Patient Journey Our social media mining confirmed the complexity of adherence challenges for people with Alzheimer’s. The resulting insights confirmed that patients and care partners: • May not communicate effectively with their HCPs because of the daily challenges of living with Alzheimer’s, and a perceived low efficacy of treatment • May not understand treatment decisions, what to expect with treatment, or the importance of communicating effectively with the HCP prior to stopping treatment • Struggle to coordinate multiple care needs, such as driving, home care, and legal and financial issues • Often seem overwhelmed by having to manage care and treatment decisions • Do not seem to know what to expect with treatment benefits and side-effects (and when to expect them) and what they should do about side-effects The journey illustration helps summarise the insights that we gleaned. The journey also emphasises the complexity of the decision-making that care partners and people with Alzheimer’s face early in the disease. Treatment is just one of many critical decisions they must confront. A journey illustration helps reinforce the importance of developing adherence programmes focused on more than taking medications (such as reminder programmes). Effective adherence programmes must also address the other factors in a person’s life that can influence adherence. An Additional and Unexpected Barrier: Mistaking Symptoms for Side-Effects While analysing our social media verbatims, we noted that treatment may be stopped because of an Alzheimer’s symptom rather than a treatment side-effect. We hypothesise that patients and care partners failed to distinguish between symptoms and side-effects, which can be similar or even identical. Our theory is supported by the following comments: “They did add another Alzheimer’s medicine, but she was not well on it, so I took her off after one day.” “He was put on Brand Y last year and improved, but now he started complaining he was tired and didn’t sleep last night.” “They put her on Brand X, and she is having delusions and trouble talking.” “She has been on Brand X for five years but started with aggression, so we stopped it.” If people with Alzheimer’s stop treatment because they mistake a disease symptom for a treatment side-effect, a significant gap exists in current patient education programmes and materials — a gap that might not have been revealed without social media research.

social media conversations •H  elp patients and care partners coordinate care after diagnosis and throughout treatment • Support effective patient-HCP dialogue throughout treatment to support informed treatment decisions Conclusion Educational content derived from social media insights promotes effective dialogue between patients, care partners, and the healthcare team. In turn, this may increase awareness and understanding of barriers for patients and care partners, and help them work with their healthcare team to make informed treatment decisions. Our analysis demonstrates the value of online listening and its potential for improving treatment outcomes. Online communities are an inexpensive source of untapped patient and care partner insights in discussions driven by patients and care partners themselves, versus an outside source. HealthEd found that this unstructured space can uncover unique barriers that can drive potential innovation and add another layer to existing findings from structured research. And the insights are available for analysis immediately. The benefit of this social media lens can be significant when marketers try to understand the needs of patients and care partners living with complex disease states such as Alzheimer’s. In a way, social media conversations are like gems lying just below the surface, waiting for marketers who recognise in educational gaps the opportunity for improving outcomes. Once those gaps are identified, strategic solutions can be crafted to engage patients and care partners hoping to connect with others to find answers to their problems. Our findings uncovered interesting opportunities and underscored our belief that online listening, when done well, can help produce tactics that can in turn improve outcomes for patients, care partners, healthcare providers, and marketers. To learn more about how social media impacts the patient experience, visit Note: This analysis was based on raw conversations in the public domain of social media in which all personal identifiable information was stripped. HealthEd has in place standard operating procedures to protect and respect the privacy of patients. Chris Kelly, MEd, MA, is director of health education at HealthEd, where he leads the development of a wide variety of patient education programs. He has also worked as a special care manager and counselor for people with Alzheimer’s disease. Email:

Using Social Media Insights to Build Innovative Solutions After we find an unexpected barrier to adherence, our next step is to develop innovative solutions to help patients, care partners and HCPs overcome that barrier. The goal is to fill the educational need related to adherence and drive positive treatment outcomes through tactics and strategies that: • Speak with appropriate language and tone that align with

Journal For Patient Compliance Strategies to enhance Health Outcomes 39


Case Study: Using Relationship Marketing to Drive Patient Adherence in a Chronic Disease State It has been stated in the pharmaceutical industry that the next big “blockbuster” might be patient adherence in a chronic condition. The problem is how does the industry accomplish that effectively and efficiently. How can it work? What is the process? What will the results be? If pharmaceutical companies can drive adherence and improve patient outcomes, it will likely help reduce costs throughout the healthcare system and help create a winwin-win scenario among consumers, professionals and payers. To answer the questions above, let’s look at a case study that accomplishes improved adherence and helps creates the win-win-win scenario between the three key stakeholders. Case Study Type 2 diabetes meets the criteria, since nearly 26 million people in the US have diabetes, and approximately 90% of them have type 2. Each patient has different behavioural motivators and informational needs that must be addressed when trying to move them along the continuum to ongoing adherence. The company wants to motivate prospects to discuss the product with their doctors and ask for it. However, the overarching objective is to support patients on therapy, to reinforce lifestyle modifications, maintain adherence and achieve successful outcomes. The company needs to implement a relationship marketing (RM) programme with prospective patients and current patients. In order to create an RM programme, insights must be gained from research; behavioural modeling and segmentation need to be utilised to architect a programme that meets the needs of the patients. The programme itself includes multiple communication channels to drive awareness of the disease and medication, timed communications to correspond with physician visits or the critical adherence drop-off points, information-rich resource centres, and surveys at key points to continually learn more about the patients. Furthermore, each communication is aligned with the programme’s mission: small, positive steps, taken consistently, yield health rewards. For prospects, one small step might be asking their doctor about the drug. For patients already on product, that small step might be a refill reminder. The company had an increase in usage of over 50%, while patients were engaging with the communications at rates well above the industry averages. The survey feedback has been highly favourable, indicating that the programme 40 Journal For Patient Compliance Strategies to enhance Health Outcomes

is helping to address patient needs. Patients participating in the programme are converting to treatment at a higher rate than people who are not in the programme, and even more importantly, patients participating in the adherence programme are staying on therapy longer. Conclusion The process is in place to drive the win-win-win scenario, and the basic tools are well researched. It’s a matter of using the process in the right situations, customising the content to the issues surrounding the disease state, and meeting the needs of all the stakeholders to drive successful patient compliance through an RM programme. Kevin Dunn, Vice President of Global Brand Strategy The Agency Inside Harte-Hanks. With more than 20 years’ experience in healthcare marketing, Kevin develops strategic plans for patient acquisition and adherence programs, and integrated HCP direct marketing campaigns. Kevin has worked at BristolMyers Squibb, Vox Medica and Zimmer in a variety of marketing roles, and holds an MBA from Kent State University. Email: Volume 1 - Issue 2


Fundamental Progress in Investigating Drug Resistance with Electronic Multidrug Compliance Monitoring (e-MCM) Background and Purpose Current definitions of drug resistance are shaped by the pharmacotherapeutic fields they occurred in. They usually mention various contributing factors and refer either to the clinical or the biomarker level. Particular attention has been attracted by antiplatelet resistance, a phenomenon with clinical, cellular and pharmacogenetical contributors. However, the impact of every single factor to antiplatelet resistance in outpatients under prescribed antiplatelet therapy has not been comprehensively evaluated so far, neither has the temporal pattern of drug intake been studied as a possible contributor. Methods We propose generally applicable definitions of drug resistance, therapy failure and a classification of contributing factors to drug resistance. We introduce a study design with the use of blisterpacks in a target population (i.e. patients with a prescription of antiplatelet drugs), filled with the entire oral medication regimen, and equipped with electronic multidrug compliance monitoring (e-MCM) allowing thus to evaluate in a stepwise way the impact of the contributing factors (e.g. potential drug-drug interactions, genetic polymorphism) on biomarker outcome (i.e. in vitro platelet aggregation), with proven intake of the polytherapy. Discussion and Conclusion Drug resistance should be judged with the knowledge of the contributing factors and in the context of a patient’s polytherapy under daily life conditions. The use of electronic multidrug compliance monitoring (e-MCM) allows the ruling out of non-compliance and the evaluation of the impact of potential drug-drug interactions on biomarker outcome. Pharmacogenetic testing may thus be restricted to those patients with a persistent lack of response, and the impact of the genotype may be interpreted within patients’ specific clinical context. An evidence-based optimisation of the therapy in case of insufficient biomarker response may thus be given, and the intervention can be stratified according to the identified contributing factors. The debate may then be opened on the clinical benefit and the cost-effectiveness of practices currently used to overcome insufficient effectiveness solely based on biomarker findings. Keywords Compliance, drug resistance, electronic multidrug compliance monitoring, pharmacological biomarker. 42 Journal For Patient Compliance Strategies to enhance Health Outcomes

Background The term “drug resistance” has emerged from antibiotic and anticancer therapy and has been discussed in many fields of pharmacotherapy, such as antihypertensive drugs1, antiepileptics2,3, antidepressants4, lipid modifying therapy5 and antiplatelet medication6-8. “Drug resistance” was introduced as a Medical Subject Heading (MeSH) in 1972 and refers to a “diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug”. This circumscription provides a short and global definition of the phenomenon, but does not specify the clinical context under which resistance is observed. Furthermore, the definition omits to mention if the effectiveness is measured on a clinical level (e.g. mortality) or on the surrogate marker level. The term “drug resistance” has further been shaped by various authors in the context of their specific field of interest. The different proposed definitions have some basic features in common, like the clinical relevance of drug resistance, its multifactorial aspect, and its detection through pharmacological biomarkers1-8, but no generally accepted concept of drug resistance has emerged. Antiplatelet Drug Therapy for the Investigation of Drug Resistance Dual antiplatelet therapy with aspirin and clopidogrel is a wellestablished regimen in the prevention of stent thrombosis9, whereas aspirin has proved its efficacy in the primary and secondary prevention of cardiovascular and cerebrovascular events10. Up to 20% of patients experience recurrent cardiovascular events despite dual antiplatelet therapy after percutaneous coronary intervention11. These incidence rates have raised the question of antiplatelet drug resistance, which is characterised by persistent in vitro platelet aggregation. The term “antiplatelet resistance” describes “a phenomenon of measureable, persistent platelet activation that occurs in patients with prescribed therapeutic doses of aspirin”12. This definition is restricted to a biochemical phenomenon and includes any factor liable to compromise the biomarker outcome, including clinical factors that reduce drug exposure like non-compliance or poor absorption. Clopidogrel resistance received special attention and was differently named “nonresponsiveness”13 or “variability in platelet response”14. The phenomenon has been associated with CYP2C19 loss-of-function genotype15 and with drugdrug interactions affecting CYP2C19 and CYP3A4 metabolic capacity16-18. Further factors with possible influence on platelet Volume 1 - Issue 2


activity were described, like tobacco smoking19, diabetes mellitus20 and systemic inflammation with increased platelet turnover21. None of these factors emerged as the most likely cause for the unmet clinical outcome, but their effects on in vitro platelet aggregation are evident. Non-compliance must be generally suspected when patients under antiplatelet therapy do not display the expected in vitro platelet inhibition. Non-compliance has been described as a contributor of outstanding impact in aspirin therapy22, with a prevalence of 22% in a cohort with manifest coronary artery disease and stroke23. However, when aggregation is inhibited, this means that an appropriate amount of the prescribed drug has been taken to produce the pharmacological effect, not that the prescribed regimen has been adhered to24. The contribution of non-compliant behaviour to antiplatelet resistance in outpatients under prescribed antiplatelet therapy has not been evaluated so far. Definition of and Contributing Factors to Drug Resistance “The absence of the expected biomarker response under (adequately) prescribed therapy (in correctly diagnosed patients)” may represent the cornerstone of a general definition of drug resistance. Consequently, we support that an unfavourable clinical outcome should be addressed as “treatment failure”25 while “drug resistance” should be reserved for therapies whose efficacy can be evaluated with pharmacological biomarkers. When a patient fails to respond adequately to a prescribed treatment, either on a clinical or on a biomarker level, the physician must distinguish among different causes of variability (pharmacological, behavioural, biological). Often, a combination of factors has produced the suboptimal results. Given the above definition of drug resistance, the contributing factors can be classified into clinical, genetic and cellular factors (Table 1), as already proposed for antiplatelet resistance26. Each single factor may negatively influence the biomarker response, and the ensuing impact depends on the taken drug. In summary, we promote the comprehensive assessment of drug resistance with the evaluation of all contributing factors. To this purpose, we propose a study design with the implementation of a new compliance monitoring technology, using the field of antiplatelet resistance as a model. Aims of the Study The aims of the study of which the design is presented in this article are to identify resistance to antiplatelet therapy

in outpatients with a prescription of antiplatelet agents, and to assess all factors that compromise the biomarker response, i.e. the platelet aggregation. Table 1: Contributing factors to drug resistance, with specific examples for antiplatelet drug resistance Factors contributing to drug resistance Factors contributing to antiplatelet drug resistance (aspirin and/or clopidogrel)25, 26 Clinical factors Failure to prescribe; Underdosing Prescription Mostly delayed or omitted doses Patient non-compliance Poor absorbance Interaction with ibuprofene (aspirin); Drug-drug interactions Interaction with PPIs and statins (clopidogrel) Tobacco smoking; Elevated body mass index Lifestyle factors Diabetes mellitus; Comorbidity Acute coronary syndrome; Genetic factors Systemic inflammation Pharmacokinetic Polymorphisms of MDR1 and CYP isoforms Pharmacodynamic Polymorphisms of P2Y12 and GPIIb/IIIa Cellular factors Cell turnover Increased platelet turnover Adaptive cellular mechanisms Increased ADP exposure Up-/down-regulation of cell Up-regulation of ADP-mediated pathways metabolism

Methods Blisterpack and Compliance Measurement Technology We chose a commercially available weekly blisterpack with 7x4 compartments (Pharmis GmbH, Beinwil a.S., Switzerland), filled with the entire oral medication regimen of the patient (Rx and OTC drugs). The back of the blisterpack is covered with a clear, self-adhering polymer foil (provided by ECCT B.V. Eindhoven, NL) with loops of conductive wires and connected to electronic components (Fig. 1). The attached microchip measures the electrical resistance, and records the time of its changes when a loop is broken, i.e. when a cavity is emptied. The data is transferred with a wireless communication device (near field communication) to a web-based database. This electronic multidrug compliance monitoring (e-MCM) system enables the monitoring of the entire pharmacotherapy, and thus assessment of compliance behaviour and drug-drug interactions. Recruitment and Inclusion Criteria Patients are recruited at their local general practitioners (GP) surgeries during a routine consultation. Inclusion criteria are the prescription for aspirin and/or clopidogrel for the prevention of primary or secondary atherothrombotic events (cardiovascular, stent thrombosis or cerebrovascular event), Journal For Patient Compliance Strategies to enhance Health Outcomes 43

Therapeutic or for the treatment of peripheral arterial occlusive disease (PAOD), and the patient’s agreement to get a weekly blisterpack with electronics (e-MCM) prefilled with all orally administered drugs and to leave all extra drugs at the study centre. Exclusion criteria are acute cardiac symptoms, residence in a care home or receiving home care, and lack of discernment to manage one’s own pharmacotherapy. The use of a pill organiser is not an exclusion criterion.

Figure 1

Biomarkers for Antiplatelet Therapy Historically, platelet aggregation in platelet-rich plasma was the method of choice to assess in vitro platelet activity27. In recent years, new assays have become commercially available. Raising evidence supports the introduction of multiple electrode aggregometry (MEA, Dynabyte, Munich, Germany) for the measurement of platelet aggregation and the prediction of the clinical outcome28. In the described study design, MEA is applied to measure in vitro platelet aggregation. The MEA instrument allows two ways to express the AUC: as arbitrary aggregation units (AU · min) or as units (U), whereas 10 AU · min correspond to 1 U. The cutoff value was set at 54 U29. Study Plan and Stepwise Assessment of Contributing Factors At visit 1, demographic data including smoking status, educational level and social background is collected; baseline laboratory data including platelet aggregation is measured, and the individualised blisterpack for one week is delivered. Patients are informed that their drug intake will be electronically monitored, and advised to take their drugs as they were instructed in usual care. Patients’ extra drugs are stored at the study centre during participation, thus rendering parallel drug consumption impossible. At visit 2, one week later, in vitro platelet aggregation is measured and serves to dichotomise the study cohort into subjects with a) sufficient and b) insufficient platelet inhibition. The latter group will get another week of compliance-monitored therapy, with an additional direct observation (DOT, directly observed therapy) of the doses containing the antiplatelet drug on five of seven days. The assessment of drug-drug interactions and pharmacogenetic polymorphisms is performed in all patients. Sample Size Estimation The incidence of antiplatelet resistance in patients with a prescription for aspirin and/or clopidogrel varies widely (8 - 45%)12. For circumstances as defined in our study, an incidence of 20-30% seems reasonable. The presence of main contributing factors in the general population is assumed to 44 Journal For Patient Compliance Strategies to enhance Health Outcomes

be 15% for the loss-of-function genotype (g), 60% for drugdrug interactions (d), and 20% for comorbidities (c). Thus, the codes of the different patient groups and the rates of non-responders would be g0d0c0 (2%), g0d0c1 (60%), g0d1c0 (15%), g0d1c1 (65%), g1d0c0 (55%), g1d0c1 (75%), g1d1c0 (75%), g1d1c1 (90%), with 1 if the factor is present, and 0 if the factor is absent. The primary analysis should demonstrate that the main contributing factors have the expected influence on non-response. A Monte Carlo simulation with adjusted sampling for the estimated overall incidence of non-response resulted in a required total of 493 evaluable patients to achieve a power of 80% as for the primary analysis. Expected Results Baseline platelet aggregation at visit 1 mirrors the effectiveness of a patient’s polytherapy, i.e. drug efficacy under daily life conditions. We expect the values after one week to show an improved platelet inhibition, independently of the baseline value (and very likely because of the Hawthorne effect), and to draw conclusions on the optimal temporal pattern of drug intake on biomarker outcome with antiplatelet drugs. With proven compliance by means of e-MCM, we will be able to quantify the clinical, genetic and cellular factors other than non-compliance in patients with insufficient platelet inhibition under aspirin and/or clopidogrel. With the tracking of the entire pharmacotherapy, we will be able to evaluate the impact of drug-drug interaction on the biomarker response, and to make recommendations for action when platelet inhibition is insufficient. We expect differences between both groups (aspirin and clopidogrel) in frequency rates, with a greater importance of pharmacogenetic polymorphisms and drug-drug interactions under clopidogrel therapy. Noncompliance is assumed to have a similar impact on in vitro platelet inhibition for both antiplatelet drugs. Volume 1 - Issue 2

Therapeutic Discussion and Conclusion The use of electronic multidrug compliance monitoring (e-MCM) for the assessment of drug resistance allows us to rule out non-compliance and to evaluate the impact of potential drug-drug interactions on biomarker outcome. Pharmacogenetic testing may be restricted to those patients with a persistent lack of response. An evidencebased optimisation of the therapy in case of insufficient biomarker response is thus given, and the intervention can be stratified according to the identified contributing factors. The efficacy of the intervention can then be estimated with the biomarker outcome. In essence, the switch to another drug can be proposed only in case of proven inefficacy (genetic polymorphism, comorbidity, inevitable interaction). Our stepwise approach to identify and assess drug resistance in individual patients is applicable to many therapeutic settings, like treatment of dyslipidemia, hypertension, osteoporosis, and congestive heart failure. To our knowledge, prospective compliance monitoring in patients with antiplatelet drug resistance has not been evaluated so far; neither has the applicability of in vitro platelet monitoring with multiple electrode aggregation (MEA) in a primary care setting. Insufficiently lowered platelet aggregation with MEA is associated with an unfavourable clinical outcome and thus underlines the relevance of the finding. Stratified interventions may optimise safety and effectiveness of drug therapies under daily life conditions, and back up the utility of diagnostic strategies addressing drug resistance. Further studies are needed to evaluate the clinical benefit and cost-effectiveness of identifying and treating drug resistance in different population groups. Summary Points • We support a new definition of drug resistance and propose its attribution to an inadequate biomarker response to prescribed drugs. • Drug resistance is a phenomenon with multiple contributing factors on the clinical, genetic and cellular level. • Antiplatelet drug resistance can serve as a model for drug resistance. • The assessment of contributing factors must involve electronic multidrug compliance monitoring (e-MCM) to rule out non-compliance and to measure exposure to drugdrug interactions. • More studies are needed to evaluate the clinical benefit and cost-effectiveness of identifying and treating drug resistance in different population groups. References 1. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008;51:1403-19. 2. S isodiya SM, Marini C. Genetics of antiepileptic drug resistance. Current Opinion in Neurology 2009;22:150-6. 3. Mann MW, Pons G. La pharmacorésistance des épilepsies partielles : épidémiologie, mécanismes, pharmacogénétique, 46 Journal For Patient Compliance Strategies to enhance Health Outcomes

perspectives thérapeutiques. Neurochirurgie 2008;54:25964. 4. Fava M. Diagnosis and definition of treatment-resistant depression. Biological Psychiatry 2003;53:649-59. 5. Catapano AL. Perspectives on low-density lipoprotein cholesterol goal achievement. Curr Med Res Opin 2009;25:431-47. 6. Burns TL, Mooss AN, Hilleman DE. Antiplatelet drug resistance: not ready for prime time. Pharmacotherapy 2005;25:1621-8. 7. Oqueli E, Hiscock M, Dick R. Clopidogrel Resistance. Heart, Lung and Circulation 2007;16:S17-S28. 8. Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E. The genetics of antiplatelet drug resistance. Clinical Genetics 2009;75:1-18. 9. Steinhubl SR, Berger PB, Mann JT, Fry ET, DeLago A, Wilmer C, Topol EJ. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:2411-20. 10. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:7186. 11. Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, Bassi AK, Tantry US. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POSTSTENTING Study. J Am Coll Cardiol 2005;46:1820-6. 12. Sanderson S, Emery J, Baglin T, Kinmonth AL. Narrative review: aspirin resistance and its clinical implications. Ann Intern Med 2005;142:370-80. 13. Gladding P, Webster M, Ormiston J, Olsen S, White H. Antiplatelet drug nonresponsiveness. American Heart Journal 2008;155:591-9. 14. Jennings LK. Variability in platelet response to the antiplatelet agents aspirin and clopidogrel: mechanisms, measurement, and clinical relevance. Crit Pathw Cardiol 2009;8:20-8. 15. Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009;302:849-57. 16. Sibbing D, Morath T, Stegherr J, Braun S, Vogt W, Hadamitzky M, Schomig A, Kastrati A, von Beckerath N. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009;101:714-9. 17. Schroeder WS, Ghobrial L, Gandhi PJ. Possible mechanisms of drug-induced aspirin and clopidogrel resistance. J Thromb Thrombolysis 2006;22:139-50. 18. Lau WC, Gurbel PA. Antiplatelet drug resistance and drugdrug interactions: Role of cytochrome P450 3A4. Pharm Res 2006;23:2691-708. 19. Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol 2009;53:1273-8. 20. Angiolillo DJ, Suryadevara S. Aspirin and clopidogrel: efficacy and resistance in diabetes mellitus. Best Practice & Research Clinical Endocrinology & Metabolism 2009;23:375-88. 21. Guthikonda S, Lev E, Patel R, DeLao T, Bergeron A, Dong J, Kleiman N. Reticulated platelets and uninhibited COX-1 and Volume 1 - Issue 2

Therapeutic COX-2 decrease the antiplatelet effects of aspirin. Journal of Thrombosis and Haemostasis 2007;5:490-6. 22. Cuisset T, Frere C, Quilici J, Gaborit B, Bali L, Poyet R, Faille D, Morange PE, Alessi M-C, Bonnet J-L. Aspirin noncompliance is the major cause of “aspirin resistance” in patients undergoing coronary stenting. American Heart Journal 2009;157:889-93. 23. Serebruany V, Cherala G, Williams C, Surigin S, Booze C, Kuliczkowski W, Atar D. Association of platelet responsiveness with clopidogrel metabolism: Role of compliance in the assessment of “resistance”. American Heart Journal 2009;158:925-32. 24. P  ullar T, Feely MP. Reporting compliance in clinical trials. The Lancet 1990;336:1252-3. 25. F erreiro JL, Angiolillo DJ. Clopidogrel response variability: current status and future directions. Thromb Haemost 2009;102:7-14. 26. A  ngiolillo DJ. Variability in responsiveness to oral antiplatelet therapy. The American Journal of Cardiology 2009;103:27A34A. 27. B  orn GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962;194:927-9. 28. S ibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009;53:849-56. 29. Siller-Matula JM, Christ G, Lang IM, Delle-Karth G, Huber K, Jilma B. Multiple electrode aggregometry predicts stent thrombosis better than the vasodilator-stimulated phosphoprotein phosphorylation assay. Journal of Thrombosis and Haemostasis 2009;8:351-9. Conflicts of Interest: None declared. Acknowledgements: The authors thank Thomas Fabbro, Clinical Trial Unit, University Hospital Basel for his statistical advice and for the sample size estimation. Michel Romanens studied medicine in and specialised in internal medicine and cardiology. He works in his cardiology practice and as a consultant at the cantonal hospital in Olten, Switzerland. He is also founder of the Vascular Risk Foundation VARIFO and scientific coordinator of the national AGLA Taskforce Atherosclerosis Imaging. Email:

Dimitrios A. Tsakiris studied medicine in Thessaloniki, Greece. After residencies in internal medicine and hematology at the University Hospital in Basel, Switzerland, he worked as research associate at the Mount Sinai School of Medicine, New York, NY, USA. Since 2009, he is head of Hemostasis Lab, Laboratory Medicine, University Hospital and since 2010 appointed professor at the University of Basel. Email: Kurt E. Hersberger studied pharmacy in Basel and Zurich and received his PhD at the Swiss Federal Institute of Technology Zurich in 1992. Besides his part-time work in his own community pharmacy, 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 Department 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: Philipp Walter studied pharmacy at the University of Basel and further specialised in laboratory medicine. Parallel to his work as a clinical laboratory scientist he started his PhD thesis in 2008 at the Pharmaceutical Care Research Group, University of Basel, Switzerland. His topic on drug resistance connects pharmacy and laboratory medicine. Email:

Willem Kort holds university degrees in medicine and medical informatics. He has been involved in e-health care communications over the last 40 years. Since 1997 he is working on the commercial application of electronic compliance measurement technologies. He developed and patented technologies for the objective measurement of compliance. Email:

Journal For Patient Compliance Strategies to enhance Health Outcomes 47

Modern Technology

Technology is Good for Your (and Pharma’s) Health In the run-up to eyeforpharma’s flagship aatient adherence event: 8th Annual Patient Adherence Communication and Engagement (PACE USA), and Patients Week 2011, Andrew Tolve reports on how pharma can leverage technology to build brand loyalty among physicians and patients The face of healthcare today is a physician in a white lab coat with a stethoscope draped around his or her neck; the face of healthcare tomorrow is the mobile device in that physician’s pocket. As the internet becomes an ever-richer resource of medical information, and as mobile devices provide evergreater access, technology and health are bound to become inextricable. Apps and web-based solutions already make administering healthcare faster and more effective for physicians and engaging with personal health easier and more enjoyable for patients. “There’s clearly a revolution going on,” says Anne Wojcicki, cofounder of 23andMe. “We’re witnessing an extreme amount of interest in web-based technologies that aim to engage people in healthcare and, in the process, transform the idea of what technology and the internet can be.” Pharma has done a fair job so far of entertaining devices like the iPad for sales forces and of embracing online endeavours for marketing and patient outreach. Moving forward, those companies that piece together a nuanced understanding of how technology can be leveraged to reach physicians and patients and to create better brand loyalty will enjoy a competitive advantage. The Fitness Frontier Conventional wisdom says that technology discourages healthy behaviour. Your mind may get a good workout playing Angry Birds or perusing the web on your iPad, but your body does not. New solutions, however, prove that mainstream technologies can actually be powerful enablers of fitness and health. Look no further than the Nintendo Wii, a video game console that requires its players to be as active in their living rooms as the digital figures fighting enemies or swiping forehands on the screen. “If you look at the way Nintendo has gone about it, it’s brilliant,” says Stacey Chang, strategic lead for consumer health and medical products in IDEO’s health and wellness practice. “Wii is a lot of fun. It’s a cool, innovative technology, and as a side benefit you’re getting a lot better blood pressure.” Likewise, a raft of new apps and web-based solutions show that laptops, smartphones, and tablets can be managers and motivators of health. Lose It!, for example, makes it easy for people to calculate calories and nutritional value of meals. CardioTrainer provides a virtual training partner for personalised instruction and motivation in the gym. Keas offers step-by-step care plans that engage individuals with 48 Journal For Patient Compliance Strategies to enhance Health Outcomes

their own medical data and place them on a path toward positive health outcomes. Many of these so-called Health 2.0 solutions include a social element, with online communities encouraging people toward their goals. On, for instance, people can motivate friends by posting fitness challenges on their Twitter or Facebook walls. With Zamzee, teenagers can track their movements with “activity meters” that automatically upload their data to an online community, where they can earn points, interact with friends, and buy products from participating vendors. “So many health problems are avoidable and so many others at least can be alleviated through prevention,” says Esther Dyson, an angel investor in numerous Health 2.0 startups. “But people need the spark. They need the impetus. That’s what technology and social media can provide.” Meet the Cybernetic Physician Assistant Back in January, IBM pitted its supercomputer Watson against two of the best trivia players in the world on the game show Jeopardy. Watson won. The company followed the virtuoso performance by announcing that Watson’s smarts would soon be parlayed into “cybernetic assistants” that could retrieve information for physicians, even potentially from mobile devices. More and more technology is helping to improve the efficiency and effectiveness of physicians’ jobs. Consider the iPad, which healthcare professionals have adopted faster than any other market segment. Already physicians are using iPads in hospital settings to explain diseases to patients and to access data and records. In the US, the government has authorised up to $30 billion in reimbursements for healthcare IT systems to expedite adoption of electronic health records, further increasing the iPad’s popularity in healthcare settings. Likewise, the Scottish government has endorsed the iPhone 4 and iPod Touch as the best fit for the National Health Service, which is working on an iPhone app for access to its patient administration system. In turn, numerous tech companies have unveiled solutions that turn these tablets into sleek medical devices for physicians. The ECG app, for instance, lets physicians measure a heartbeat by simply pressing an iPhone or iPad against a patient’s chest. iAnatomy enables physicians to view cross sections of the body with real CT scans, including images of cadavers. Then there’s 3D Teeth for dentists, Eponyms for med students, and Medscape for all of the above. (Medscape is the all-purpose reference guide for clinical questions, latest procedures, and breaking medical news.) “The iPad has the potential to become intrinsic within healthcare,” forecasts David Hunt, digital director of Creative Lynx. “If that happens, iPads may be qualified as medical devices.” And tablets and smartphones are just the beginning. In the past few months scientists and engineers have unveiled Volume 1 - Issue 2

Modern Technology

“intubation robots” to automate anesthesiology and handheld sensors that can instantly detect viruses like H1N1, HIV, and Hepatitis B and C. “Imagine if you had something as cheap and as easy to use as a pregnancy test, but that could quickly diagnose HIV and TB,” says Benjamin Ross, a UC Berkeley graduate student who works on the SIMBAS Blood Analysis Biochip. “That would be a real game-changer. It could save millions of lives.” The Empowered Patient Perhaps the most eager consumers of healthy-tech solutions are patients. After all, chronic conditions can be tiresome to cope with day after day. Web-based solutions can make it easier and more fun, from sending reminders about dosages to storing data in virtual vaults that can illuminate a patient’s unique condition to a physician. The Apple App Store teems with apps targeting patients with chronic diseases. On the diabetes front, there’s Your Diabetes Guardian, Kenkou, and, for patients and caregivers in developing countries with remote access, the Dulce Wireless Tijuana Project. And that’s just a few of the many. For hemophiliacs, there’s Hemolog and HeliTrax, both of which allow hemophiliacs to manage their infusions and open up a world of personal data for doctors. “There’s so much information we can gather and infer from a log, but there’s no clear, concise way to look at it and consume it quickly,” says Michael Schultz, a hemophiliac and the founder of Hemolog. Hemolog makes it a breeze for hemophiliacs to log infusions on an iPhone or iPad, he says, and “there’s no work that has to be done by the hematologist. It’s like a cheat sheet to a quiz.” The past few years have also witnessed the rise of apps and websites that help patients be proactive about diseases, with the goal of stopping them before they ever start. 23andMe, for example, provides patients with an easy way to test their genetic predisposition to diseases and then engage in online communities and research to help find solutions to those diseases. “Our focus is giving the individual a voice in healthcare, in their own healthcare and with the research world,” says Wojcicki. “That’s the next big movement in healthcare, partnering with people as consumers instead of treating them as a patient or a human subject.” Pharma’s Tech Forecast Pharma can capitalise on the convergence of technology and health on a number of fronts. For starters, it can integrate new solutions into company departments, from sales forces to marketing teams and R&D wings. Second, it can design apps that make life easier for physicians and patients, thereby creating goodwill and brand loyalty. For physicians, Novartis already offers the GIST Calculator, Roche the Nursing ACE, and Johnson & Johnson the Psoriasis App. For patients, Merck offers iChemoDiary,

which helps patients record treatments, meds, and symptoms during chemotherapy. Sanofi’s GoMeals, meanwhile, helps diabetics access nutritional information of everyday foods and track the values of food intake. But the virtual shelves of apps stores have plenty of room to accommodate more solutions, and those that get in early have the potential to shape a clinical application or patient care for years to come. Third, pharma can look to create valuable partnerships with social communities. In an era when people congregate online around every conceivable subject, from disease to fitness, pharma companies have the opportunity to sponsor forums or listen in on the conversation. Those that do can improve their image and help the advancement of medicine. UCB epitomises this approach with its endorsement of PatientsLikeMe, where it has helped foster an online, open epilepsy community that captures real-world experiences of people living with epilepsy in the US. “What we’re seeing on our site every day is that patients are interested in learning more about their disease,” says Ben Heywood, president and co-founder of PatientsLikeMe. “By joining forces with industry leaders like UCB, we can turn up the volume of the patient voice in companies who are committed to hearing it and working toward better treatments and better care.” information on Patients’ Week and to sign up for a free webinar on Monday 19th September, go to patient-week/ For everything patient-related, join the sector’s flagship event: Patient Adherence, Communication and Engagement (PACE) USA on October 24-25 in Philadelphia. Want to know more? Contact To read our Patients’ Week stories from 2010, visit www. Andrew Tolve is an eyeforpharma staff writer. He writes frequently about the intersection of technology and Pharma, as well as about patients and creating customer value. Email:

Journal For Patient Compliance Strategies to enhance Health Outcomes 49

Modern Technology

Welcome to the Mobile Health Jungle For nearly a decade analysts have predicted mobile technologies would reshape the healthcare industry. During this period of analysis and debate, the safest place for a healthcare executive was as a spectator from a very safe distance. No healthcare organisation has yet conquered the mobile jungle. Adventures have been limited to a few exploratory pilots to test SMS messaging for compliance, some diabetes apps, and creative digital marketing scouting campaigns. However, the days of safely sitting on the sidelines are over. Seemingly overnight, the sticky tentacles of mobile technologies have wound themselves throughout the healthcare ecosystem. Empowered patients, healthcare reform, and a focus on health outcomes have opened the door to new players willing to risk much. The rapid and widespread adoption of smartphones is shaping a new generation of customer relationships that reduce healthcare costs and improve outcomes. Industry analysts predict the greatest potential for transformation is in the area of mobile health. PriceWaterhouseCoopers’ Health Research Institute estimates the annual consumer market for remote/mobile monitoring devices and services to be a $7.7 billion to $43 billion market. Industry analysts predict using mobile solutions to improve compliance is one of the fastest and most effective places to begin. But getting started is not that easy. Like it or not, pharma marketers, payers, clinical research organisations, pharmacy benefit management companies and patients have been dropped into a mobile jungle, with little navigational aid. Charting Unfamiliar Territory This article will help healthcare companies navigate through the mobile jungle, avoid unforeseen pitfalls, and return triumphant with a compliance solution that works for patients. Keep reading to discover: • The diversity of mobile compliance • Pitfalls and how to avoid them • The challenge of new mHealth species • The importance of alliances for survival • The treasure of improved compliance • Top 10 mobile survival websites Diversity of Compliance Features As you scour your survival kit in the mobile health jungle, remember to be resourceful. Improving compliance requires flexibility and an open mind. Flexibility is important because no two patients are the 50 Journal For Patient Compliance Strategies to enhance Health Outcomes

same. To maximise compliance you’ll need to offer a variety of compliance tools. For some patients, especially those that are over the age of 65, have multiple chronic diseases, are tech-averse, or are in a healthcare institution, smart pill bottles and automatic dispensers may be a better solution than smartphones. Mobile compliance solutions reach their full potential when used by patients who have chronic diseases, take multiple medications, use smartphones, and believe that changing their behaviour will improve their health. Many caregivers may seek these solutions out as well, to make it easier to care for a loved one. If mobile compliance solutions are right for your audience, the next step is to decide what compliance tools to offer. Providing simple text reminders to take pills is the easiest point to start; and they don’t require a smartphone. You can set up a simple system to send SMS reminders to any type of cell phone. You can find a number of pill reminder apps in the Apple app store. Although these SMS reminders may increase compliance, they only work with certain types of patients. Adding other types of compliance features into your mix can boost returns even more. Tracking compliance and providing patients with feedback on their rate of compliance can be highly motivating. For others, ongoing educational messages help to change behaviours. Allowing patients to set goals, like losing weight, exercising more, or lowering blood sugar levels, can help patients become more compliant with recommendations. Seeing their data charted over time can also be a big motivator in changing behaviours because it allows patients to recognise patterns. For example, it may be easier for patients to understand the connection between their high blood glucose, nasty mood, and skipped medication, when seeing their stats illustrated in a graph. Reports can also be powerful motivators for patients if a medical professional asks to see how their health is during scheduled visits. Other patients respond to financial incentives, such as rewards for reaching goals. Lastly, many patients change behaviour for the reward of social approval in communities. You’ll find a diversity of mobile health solutions to fit the wide variety of patients. The challenge for you is to select the right ones. Ideally, you’ll adopt a platform that is flexible enough to support a variety of compliance scenarios. It’s exhausting for patients to manage a scattered set of tools, and you’ll find the greatest return on your investment from an integrated mobile health solution. Volume 1 - Issue 2

Modern Technology Pitfalls of Mobile Health and How to Avoid Them Navigating through the mobile health jungle is not easy. Pitfalls are everywhere, but here are the top three to look out for: Pitfall #1: Missing the Big eHealth Picture What does this mean in regards to mobile health? This means not to focus on a small mobile application; think about an eHealth platform. Why? A single iPhone app only satisfies a niche audience. In fact more than 80 per cent of the iPhone applications released are never downloaded more than 10,000 times. Less than five per cent of all iPhone applications are used after the first six months of being downloaded. Patients want their information centralised and crave functionality. Data locked in a variety of apps and devices has limited value. An eHealth platform that consolidates patient information provides a 360-degree insight into a patient’s health. The mobile component of an eHealth platform is what drives patient engagement. Most patients are not motivated enough to log into a desktop application. Yet when information is continually pushed to them on their mobile phones, they can easily: update their status, input data, and receive tweets, alerts and reminders any time, anywhere. Mobiles build the connections that unlock the potential of eHealth. Pitfall #2: Forgetting About the Patient No matter how beautiful, technical, or medically sophisticated your application is, if patients don’t use it, your investment is wasted. Ask yourself: “Will this mobile solution actually solve a problem our patients have? Is it easy to use from the signup stage to cancellation? Is it flexible and accessible? Can they take it with them if they leave? Is it private and secure?” Whether you build, buy or rent via a Software as a Service (SaaS) model, your mobile health solution must solve the patient’s needs. Solve the patient’s problem first and you will reach your own goals of selling more medications, reducing waste or improving outcomes. Pitfall #3 - Neglecting Customer Support No matter how simple a service is, at some point users have questions. If your audience is a bit older and less tech-savvy, they may have many questions. And, they all have different expectations for customer support interactions. So, here are some things to think about: • Will you offer phone support? In-house or outsourced? • Are you going to have online documentation? Is an online support community available? • Have you considered secured account sharing for tricky support questions? 52 Journal For Patient Compliance Strategies to enhance Health Outcomes

The type of support you offer is critical. It reflects the credibility of the brand you’ve worked so hard to build. Keep Your Eyes Peeled for New Species Although you may feel left behind if you haven’t launched your iPhone app yet, staying on the sidelines may have saved you resources. The mobile technology market is highly fluid, with new players, platforms, operating systems and hardware spotted daily. While the iPhone has received most of the press, according to Chitika research in July 2011, Android took the lead. Now, the BlackBerry is an endangered species. Android may be king of the jungle today, but it’s wise to keep watch for new developments and mobile platform trends on the horizon. There is a full pipeline of new smartphones, tablets, and devices. The future of mobile health is yet to be invented. Given the fact that the mobile platform market is a moving target, you may want to outsource the risk of product development. You don’t want to spend your entire budget on one platform, to discover that as soon as you launch your customers have moved on to the next big thing. Using a company that offers mobile health solutions as an SaaS model removes most of the risk. It becomes their responsibility to stay current, to optimise the latest features, and to support your users, no matter what platform they are on. Building New Alliances for Survival You wouldn’t charter through unfamiliar territory alone, would you? So why try and tackle a mobile health solution without support? Mobile health applications (and the eHealth or customer service platform they connect to) are increasingly complex. Creating a mobile solution that manages your patient relationships to improve compliance is not the same thing as building a website, an iPhone app, a web tool, or an interactive video campaign. It’s not as simple as putting a social media strategy in place, or setting up a tweet channel to blast out health messages. The partners you have today may not be the right ones to lead you into the future of mobile health. The most important step to ensure your survival in the mobile jungle is to make sure you have a team of experts that can guide you successfully. Here are a few of the characteristics to look for as you put your team together. Marketing and Support – Building a solution is the first step, and it’s not easy. A harder task often is getting the attention, engagement, and retention of users. Getting your product into the hands of your patients is a conversation that should happen before you even start developing. The right marketing Volume 1 - Issue 2

Modern Technology partners can come up with ideas to increase adoption that can be embedded in your product. They are responsible for continually educating patients about the ongoing value. Engage them early and they will have more ownership towards successful adoption. Software Developers – When it comes to mobile health solutions, the first response is to hire a mobile expert, or mobile engineer. But it’s not that easy. There is no “magic” in the mobile title. And the most experienced iPhone developer is not going to be able to deliver a solution that supports your patient communications over the long term. The requirement is for experienced software developers. When it comes to mobile health, the phone is primarily a communications device, which enables interactive patient relationships. It is the next evolution of customer relationship management technology which has been around for decades. The ideal tech partner is someone who understands the full potential of mobile technology today, and keeps a watchful eye on the future. They should be experienced in applying technology to improve customer relationships, and knowledgeable about the transitioning healthcare environment. User Advocate – You need someone on your team that is an unwavering advocate for your customer. Their job is to ensure the solution you are building meets the needs of the patient, and actually gets used. The patient’s perspective should influence your decision from product name, to platform support, to feature set, and patient support. HIPAA, Legal, and other Regulatory Restrictions – The best regulatory experts likely come from within your organisation. No one knows better than you the complexities of healthcare regulations in your field. However, your other partners must fully support your requirements, and look for innovative ways to strike a balance between regulation and usability. Carriers – If you are using SMS to communicate with your patients, you’ll need a relationship with an SMS messaging provider. This relationship may be handled through your marketing or technology partner. The bottom line: mobile health success is a team effort. Plan to form some non-traditional alliances to achieve success. Is the Treasure Real? Risking the mobile health jungle is only worth it if your company is rewarded for the effort. Below are three studies that demonstrate improvements in medication adherence with the help of mobile health. Keep in mind that these studies are based around simple text messaging methods. They don’t include the power of rich push messaging, compliance feedback, education, and goal reporting. The full potential of mobile health on compliance is yet to be realised. 1. In October 2009, Ulla Strandbygaard, Simon Francis Thomseln and Vibeke Backer, from the Department of Respiratory Medicine, conducted a study on asthma patients and their adherence to their medications with text message reminders. The study, “A Daily SMS Reminder Increases

Adherence to Asthma Treatment: A Three-Month Follow-up Study” discovered SMS reminders improved compliance by at least 11%.

2. Also in 2009, the Archives of Dermatology published research that illustrated successful use of mHealth to improve adherence. The study, ‘Text-message Reminders to Improve Sunscreen Use’, revealed a 16% increase in sunscreen adherence with SMS reminders.

3. In April 2011, the School of International and Public Affairs, Columbia University, discovered a dramatic 50% increase in medication adherence with the use of SMS reminders. This study was analysed in Kenya and conducted over 48 weeks. “Mobile Phone Technologies Improve Adherence to Antiretroviral Treatment in a Resource-Limited Setting: A Randomized Controlled Trial of Text Message Reminders” proves to be the most promising research supporting the use of mobile health with a 50% increase in adherence with SMS reminders also.

Become King of the Jungle The rapid and widespread adoption of smartphones is shaping a new generation of customer relationships that will reduce healthcare costs and improve outcomes. How it will all play out remains to be seen; but the change is unstoppable. Healthcare executive can stay safe and fall behind, or be brave and venture ahead into the mobile jungle. Think big and move beyond your comfort zone by partnering with non-traditional players. They have the vision and technology experience to lead you on a great adventure. Always put patients first to build entirely new patient relationships that not only improve health outcomes, but place you at the top of the food chain. Top 10 Mobile Survival Websites Overwhelmed? Fear no more. Pack your survival kit with these online resources. 1. MobiHealth News - By far the most popular mHealth news resource in the industry, MobiHealthNews offers a combination of breaking news, exclusive interviews, and live Journal For Patient Compliance Strategies to enhance Health Outcomes 53

Modern Technology event coverage and industry commentary every day. Read the blog or follow MobiHealth News here: http://twitter. com/mobilehealth 2. Journal of Patient Compliance (JPC) - JPC is a peerreviewed journal for pharmaceutical companies, physicians, pharmacies, healthcare workers and insurance providers. It examines how patient compliance can be enhanced and serves as a platform for all stakeholders in healthcare to communicate, negotiate, learn and share methods and strategies to help patients adhere to their medication regime. 3. Mobile Health System - Mobile Health System is a valuable resource of white papers, media articles, and peer-reviewed literature with research on mobile and wireless healthcare (mHealth). Instead of searching for all the latest mHealth reports and presentations, David O’Reilly does it for you on this site. 4. Innovation in Medication Adherence - This LinkedIn group serves as an open discussion forum for sharing experiences, knowledge, insight, and questions related to medication adherence. 5. Patient Adherence Solutions - This LinkedIn group has more than 500+ members and is open to anyone interested in patient medication adherence. Members are strongly encouraged to submit patient adherence, compliance, and persistence articles.

Pediatrics was conducted to improve immunosuppressant adherence for pediatric patients with orthotropic liver transplants by using text messaging. Researchers observed significant improvement in medication adherence and a reduction in rejection episodes with SMS reminders for pediatric recipients of liver transplants. Pamela Swingley Enterprise software marketing executive, Pamela Swingley, has spent more than two decades helping businesses of all types adopt technologies that improve their performance. A bit more geek than she’d admit to, Pam’s contributed to the success of several tech companies, including ADP, Siebel Systems, and OnLink Technologies. Today, as the CEO of Mobile PRM, Pam’s passion is to transform patient relationships through mobile services built on a patientcentric eHealth platform that delivers improved outcomes at a lower cost. Mobile PRM’s suite of patient relationship management services help to improve medication adherence, provide treatment feedback, reduce patient acquisition costs, disseminate health information, and facilitate market research. Most importantly, Mobile PRM helps to keep people healthier. You can try the company’s eHealth solutions at www., where it’s fast and free to get started. Or, visit to learn how Mobile PRM is transforming patient relationships across the healthcare ecosystem. Email:

6. Follow Mobile PRM on Twitter - The experts that are transforming patient relationship management through mobile communications deliver fresh mHealth news daily on Twitter. Don’t miss their free eBook, “How to Profit From the mHealth Revolution.” 7. Follow Mobile Health Watch News – Mobile Health Watch brings you the latest news and resources dedicated to point of care and mobile health. 8. “The Power of Mobile – Pew Internet Research 2010” Susannah Fox rocked the healthcare industry with the release of this report where she declared the “Online Access Revolution” completely over. This thorough report offers a plethora of evidence on why our healthcare industry must embrace mobile. 9. “Development and Validation of Motivational Messages to Improve Prescription Medication Adherence for Patients with Chronic Health Problems” - The objective of this 2011 report was to improve on previous medication compliance strategies, with SMS communication. Although more research is warranted to test the use of these motivational messages for medication adherence, this report provides valuable insight into what factors affect patient behaviour. 10. “Improved Adherence and Outcomes for Pediatric Liver Transplant Recipients by Using Text Messaging” – This 2009 study by the Official Journal of the American Academy of 54 Journal For Patient Compliance Strategies to enhance Health Outcomes

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Drug Delivery, Drug Packaging, Labelling & Dispensing

What Other Factors can Complement Packaging Design to Drive Greater Compliance? In July the UK’s NHS Information Centre revealed that the number of prescriptions dispensed outside hospitals increased by almost 70% between 2000 and 2010. In 2010, nearly 927 million items were dispensed — up 4.6% on 2009 and representing an average of 17.8 items per head of the UK population. The total net cost of the ingredients was £8.8 billion. The figures received widespread publicity, as one would expect. Yet with the inclusion of one additional statistic — that around 20% of prescriptions dispensed are never cashed — the public interest might have been even greater. It might have been greater still with the addition of the World Health Organization’s estimate that around 50% of patients are non-adherent to medicines, and the fact that non-adherence costs Germany around 15 billion Euros, while non-compliance in the United States results in $100 billion a year in avoidable hospitalisations and $177 billion in total direct and indirect costs. Readers of the Journal of Patient Compliance are, by definition, familiar with these big numbers, but to someone like myself, who is less immersed day-to-day in combating noncompliance, they are quite shocking. Of course, many factors influence a patient’s ability or willingness to adhere to medication, and the industry now recognises there is an urgent need for improvement. Recent evidence into patient non-compliance is now starting to focus more heavily on their cognitive behaviour, which sees two distinct drivers; unintentional, whereby patients just don’t really want to take their medication, to the more dominant driver and intentional, which is founded on a patient’s beliefs and motivations. These may be religious in origin, passed down from parents or across by peers, or acquired from the media and the internet. With so much information available to patients coming from so many directions, even before being prescribed medication, they are likely to have already formed their own opinions driving their behaviour towards compliance. As healthcare packaging solutions providers, Brecon Pharmaceuticals continually review market requirements and have constantly applied our expertise in helping counter the more practical problems patients face, such as forgetting to take medicines when they should, or finding it difficult to open containers or understand instructions — increasingly common problems as populations age and demographics alter due to immigration. Much of the design and development work undertaken by our specialist pharmaceutical packaging division touches on these aspects of compliance, and as a result, we are able to offer a wide range of innovative compliant-focused packaging solutions, such as the IntuiDose and Burgopak products. However, in order to affect a more positive change towards greater patient compliance, now is the time for all stakeholders to work more closely together to deliver a more unified and 56 Journal For Patient Compliance Strategies to enhance Health Outcomes

watertight approach. Greater patient/clinician interaction would help educate both parties and understand the drivers to compliance. This, coupled with more widespread access to drug information online, and personalised communication to patients addressing their individual concerns, down to the design, detail and delivery of the package itself, should all work towards the objective of increasing patient compliance. Generics Add a Whole New Dimension All these influences are hard enough to combat without the addition of a whole new dimension in the form of generic Volume 1 - Issue 2

Drug Delivery, Drug Packaging, Labelling & Dispensing

substitution of branded medicines. In the drive to control public heath budgets, generics offer an inexpensive alternative to branded medicines, saving patients and governments money — the UK figures published in July showed that 67% of all prescription items were dispensed as generic medicines, yet represented just under 30% of the total cost. However, evidence is emerging that generics are undermining efforts to increase compliance, and thus increasing costs. A body of evidence is building in Norway, where pharmacies were permitted to switch to generic drug equivalents in 2001. Ten years on, investigation into generic drug use has identified erroneous use of medication as a result of confusion over the variety of products available from pharmacies. For example, in 2010, 10% of a sample reported using two equivalent generic drugs at the same time, and a 2009 study found 5% of a hypertensive patient population reported using two comparable generic drugs concurrently. Although researchers have been unable to show unambiguously that generic substitution has led to an increase in adverse drug reactions (ADRs), since Norway did not encourage ADR reporting until January 2005, it appears likely that introducing the generic option created potential for confusion in patients. A number of factors contribute to this potential. The 2010 study, by Helle Håkonsen and Else-Lydia Toverud, looked into the impact of generic substitution on drug adherence in Pakistani immigrants living in Oslo. Its overall conclusion was that ‘generic substitution may have a negative effect on drug adherence… because of concerns and misconceptions, including confusion with regard to counterfeit drugs. Problems result primarily from inadequate information caused by language barriers but also from culturally conditioned views on encounters with the healthcare system.’ These issues translated into significant non-compliance, with 31% deliberately abstaining from taking their medicines now and again. Speaking as a packaging specialist, however, the most interesting findings in the study related to the role of packaging and branding in encouraging — or discouraging — compliance, as described by Håkonsen and Toverud: Of those who had had their drug(s) substituted in the pharmacy, 26% found it more demanding to keep track of their medication after the switch since they no longer knew their medication by name or appearance. It became difficult to recognise the drugs and know which drugs the new ones were replacing or for which purpose they were to be used. This was an extra challenge for those who were not literate or had poor eyesight. Fifty percent had noticed that the non-branded product had a different shape, size, or colour compared with the brand-name product they had received previously. Some commented on the convenience of a blister package over a box container since they were easier to carry with them and also more hygienic to use.

Is it fanciful to suggest that simply by paying more attention to the packaging of generic medicines, the pharmaceutical industry can strike a major blow in the cause of increased patient compliance? Personally, I believe the answer is that all stakeholders have a part to play to address a patient’s intentional drivers, including the clinicians and the drug manufacturers, as well as the packaging solutions providers. Branding and packaging certainly influence the choices we make in almost every area of our lives today, so by ensuring the medication is packaged alongside meaningful information, instruction, support and advice, why should it not affect decisions on something as important as our health? The answers to these and other questions may not be long in coming. Again, I turn to the example of Norway, where a team at the Centre for the Study of Human Cognition at the University of Oslo is collaborating with the Norwegian Medicines Agency in a project to assess whether the regulation of the design of pharmaceutical packaging can increase medication adherence and decrease errors. One component of the study is a cognitive test to measure the participant’s ability to discriminate between similar and dissimilar products. Using both generic and branded drugs, the experiment varies the packaging to determine what is most effective. The ultimate objective of the study, with which we at Brecon are cooperating wholeheartedly, is to provide scientific support for implementing new design ideas and stimulating a campaign for change in the packaging of pharmaceuticals across Europe. It is a bold but admirable ambition, and I for one will watch its progress with interest and excitement. Wouldn’t it be ironic if one of the best ways of increasing patient compliance had been staring us in the face all the time? Steve Kemp has over 15 years’ experience of pharmaceutical packaging. He is Business Development Director at Brecon Pharmaceuticals, a post he has held since joining the company in 2001. Prior to joining Brecon, he was Commercial Services Director at PCI/Unipack, subsequently Cardinal Health and now Catalent. Steve is Vice-Chairman of HCPC Europe, a commitment that recognises his personal conviction that patient compliance is one of the key issues facing the pharmaceutical sector - improved compliance results in better outcomes for the patient and the pharma industry alike. He believes that pack design and format can play a crucial role in prompting patients’ adherence to their medication. Brecon Pharmaceuticals values HCPC Europe as a forum to meet with like-minded representatives of other aspects of the packaging supply chain to exchange ideas to further the cause of patient compliance. Email: Journal For Patient Compliance Strategies to enhance Health Outcomes 57

Case Study

A Hypertension Patient Support Programme in the Philippines to Improve Adherence and Outcomes Hypertension is a chronic, progressive cardiovascular disorder affecting 11.5 million Filipinos, according to recent data released by the Philippine Society of Hypertension (PSH).1 Despite this extensive prevalence, up to 25% of those affected are unaware of their condition.2,3 Statistics show that approximately 31% of patients with hypertension remain untreated, yet even in those who are treated, only 45% have it controlled.4 This means that blood pressure is not adequately controlled in the majority of adult patients with hypertension. A recent meta-analysis of 61 prospective studies, accounting for over one million adults, demonstrated that, for each 20 mmHg increment in systolic blood pressure or 10 mmHg in diastolic blood pressure, there was a twofold increase in mortality secondary to ischemic heart disease, stroke or other vascular causes.5 Further analysis of 14 antihypertensive drug clinical trials demonstrated that the degree of reduction in hypertension directly correlates with decreased morbidity and mortality from cardiovascular disease, particularly with regard to systolic blood pressure reduction.6 Given the magnitude of this problem, there is a clear need to treat hypertension and associated comorbidities more aggressively with the aim of reaching target blood pressure goals as quickly as possible in the hopes of reducing target organ damage. Furthermore, adherence to antihypertensive mono-therapy regimens has been shown to be poor in both prospective and retrospective studies, and steadily decreases over time, even in populations with access to healthcare.7-9 Adherence is negatively affected by numerous factors, including difficulties in managing treatment regimens that include multiple medications or multiple doses, cost and accessibility issues and socio-demographic factors as well. This specific hypertension programme is a patient support programme introduced in the Philippines for hypertension patients, and the objective of the programme is to improve adherence and compliance of the patients there by improving long-term outcomes. Methodology Any patient can enter into this programme when he/she goes to a designated chain of pharmacy to purchase the medicine. A patient fills in the hypertension programme enrolment card with his/her information, and the patient is then enrolled into this programme. At the time of purchase of medication, the patient swipes the card and this data is captured electronically. In the backend database, all the cards filled in by the patients are digitalized, and this is a master database with patient details. Every time the patient purchases medication, the card is swiped in the designated pharmacy and data is captured electronically. This purchase data is mapped with patient data wherein patient details (mobile phone number) and card numbers are matched. In short, apart from convenience in 58 Journal For Patient Compliance Strategies to enhance Health Outcomes

purchasing medication and getting discounts on purchases, this programme’s main objective is to improve medication adherence. The drive, which will motivate and keep patients informed about the programme, was essential to make sure that patients adhere to, and regularly obtain, the medication. Randomisation The mode of intervention selected is regular SMS alerts on the mobile phone of the registered patient. These mobile alerts are in the form of refill reminders and motivational/educational Volume 1 - Issue 2

Case Study

Outcomes In total, 3238 patients in the intervention group purchased the medicine, while 3203 patients in the control group purchased the medicine. The total number of tablets purchased was 179,137 and 167,667 in the intervention and control groups, respectively. Average purchase was found to be higher in the intervention group by approx 3%. Conclusion The above results suggest that intervention in the form of simple SMS reminders and health tips resulted in a 3% increase in the average purchase among patients. This 3% directly adds to the bottom line of pharmaceutical companies with very low investment in a patient adherence programme. Simple measures like mobile SMS can be used in a costeffective way to improve medication adherence in diseases like hypertension.

SMSs. The refill reminders are sent based on the purchase data. All the interventions were in the form of mobile alerts and we have divided patients into two groups: 1) Control group: Patients who do not receive mobile alerts. 2) Intervention group: Patients who receive mobile alerts. Only patients enrolled in the intervention group will receive SMS alerts, while patients enrolled in the control group will not receive any SMS alert.

References: 1. w Accessed July 25, 2011. 2. A  merican Heart Association. Statistical Fact Sheet Disease/Risk Factors. 2009 Update. High Blood Pressure — Statistics. heart/1236204702332HBP.pdf. Accessed May 5, 2009. 3. Ostchega Y., Yoon S.S., Hughes J. et al. (2008). Hypertension awareness, treatment, and control -- continued disparities in adults: United States, 2005-2006. NCHS Data Brief. Hyattsville, Maryland: National Center for Health Statistics. 4. Cutler J.A., Sorlie P.D., Wolz M. et al. (2008). Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 19992004. Hypertension. 52(5):818-827. 5. L ewington S., Clarke R., Qizilbash N. et al. (2002). Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 360:1903–1913. 6. Staessen J.A., Wang J.G., Thijs L. (2003). Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens. 21:1055– 1076. 7. Payne K.A., Esmonde-White S. (2000). Observational studies of antihypertensive medication use and compliance: is drug choice a factor in treatment adherence? Curr Hypertens Rep. 2:515-524. 8. B  ramley T.J., Gerbino P.P., Nightengale B.S. et al. (2006). Relationship of blood pressure control to adherence with antihypertensive mono-therapy in 13 managed care organizations. J Manag Care Pharm. 12:239-245. 9. D  iTusa L., Luzier A.B., Jarosz D.E. et al. (2001). Treatment of hypertension in a managed care setting. Am J Manag Care. 7:520-524. Journal For Patient Compliance Strategies to enhance Health Outcomes 59


Emine Teyze and The Devil’s Machine This is not a story. This actual event happened in Datça, Turkey. Upon reading it, a lovely smile may come to your face. My brother’s wife related this incident to me the day after it happened. It would give me great pleasure to share it with you… The word “Teyze,” -meaning aunt- is used after the names of elder ladies in Turkey. Like “Emine teyze,” Fatma teyze” etc. So here, I’ll call the main character of this event “Emine Teyze.” That means “aunt Emine.” Emine Teyze has been living alone in a house up at the slope of lskele district of Datça for fifteen years. She doesn’t consider herself really living alone, as her son and his family live above her on the second floor. She takes care of herself, keeps her house very tidy, and her garden properly tended. She is seventy eight but appears to be younger than her age. During the past year, she has been diagnosed with high blood pressure and takes a daily pill to keep her blood pressure normal.

Emine Teyze slowly walked back up the steep slope to her house feeling discouraged to return home empty handed. On her way home she stopped at her neighbor’s home to see “Fatma Teyze.” Fatma Teyze, age 96, lives alone in a single room. She still cooks, clean and visits with her sons. Emine Teyze quickly relayed what had happened at the pharmacy. After hearing the story, Fatma Teyze said, “One time, I heard something about those machines. They know everything and they never tell a lie. If you have six more

A few years ago The Social Insurance Office started a system to prevent the wastefullness of medications. Under the new system when a prescription is written indicating one pill per day for a month, thirty pills are indicated on the prescription and entered into a computer system used by the pharmacies. A patient is not able to get more pills until the thirty day period ends. If a patient goes to a doctor on the 25th day of his first prescription order, the doctor will gladly renew the prescription; however it cannot yet be filled by the pharmacist until all the pills are finished on the 30th day. So on the 25th day, the pharmacist will check his computer and tell the customer to come back five days later, after the first prescription has ended. Our Emine Teyze being a tidy and well organized woman wanted to renew her prescription earlier, until she was confronted by that Satan Machine! Computer! While still having six pills left from her first prescription, she went down to the Hospital, saw her doctor and received a prescription renewal for the next thirty pills. With her prescription in hand, she walked cheerfully to the pharmacist. Upon handing the renewal prescription to the pharmacist, he checked it with the computer, turned to the Emine Teyze and said: “You have six more pills left; I cannot give you another month’s supply until you finish them. You must return in six days.” Emine Teyze’s face reddened. She extended her open hands toward the computer and said: “Look, my son, I don’t have any pills with me.” The pharmacist replied: “Okay, you may not have them on you, but the computer says you have six more pills. You have to go and check out your house because the computer doesn’t lie.”

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pills in your house, the machine knows it. Now, you must use your head. Tomorrow morning collect all the pills that you have and bring them to me, then you go to the pharmacy. I will keep them here. When you haven’t any pill in your house, the machine will verify this and say that you do not have any pills in your house. Okay?”

with her neighbor’s advice. Next day early in the morning she awakened, had her breakfast and after consuming her daily pill, she looked in the pill box. There were only five pills in it. By nine o’clock she was out of her house to go to pharmacy. On her way she stopped at Fatma Teyze’s home, and after saying her “Good Morning” she gave her the pill box.

Emine Teyze found this to be sound advice, and decided to do so next day. Having had her Turkish coffee with Fatma Teyze she left for her home. She slept very well that night

She slowly walked down to the same pharmacy and waited her turn. When her turn arrived, she walked up to the pharmacist assistant who was sitting in front of that “Satan machine!” Being there early in the morning, the pharmacist himself hadn’t arrived yet, but one of the girls who worked at the pharmacy was taking care of the customers. She took the Emine Teyze’s prescription, entered it in the computer and a little later replied: “Teyze! You still have five unused pills.” After hearing what the pharmacist’s assistant had said, Emine Teyze murmured to herself: “This devil also counts the pills I consume daily.” Looking directly into the girl’s eyes she said aloud this time: “Your machine is not telling the truth today, it is telling lie. There aren’t any pills on me and there aren’t any pills in my house today, because I took all the pills to my neighbor’s house. Yesterday, your machine was telling the truth, but today it is telling a lie.” The pharmacist tried to explain the matter, but Emine Teyze didn’t want to listen. So what could she do? She had to come back five days later. Before walking out of the pharmacy, she glared at the “liar computer” with anger. On her way home she talked to so many locals that half of the local population of Datça heard the story on the same day. I think I was a little late to hear it, because I didn’t hear it until the third day! Now you are the latest ones hearing this. Because I am telling to you now… MediciGlobal’s Nick Halkitis is pleased to bring another one of Nihat Akkaraca’s anecdotal tales; Emine Teyze and the Devil’s Machine. Before joining MediciGlobal, and applying his vast eMarketing skills to patient recruitment for clinical trials, Nick published the well recognised English speaking newspaper and website, called Symi Visitor in Symi Island, Greece, located just 3km from the coastline of Datca Turkey. Nick and Nihat worked collaboratively to create Peace Day, bringing together residents from Symi Island, Greece and Datca, Turkey to celebrate the joy of peaceful neighbours. Every year, for over a decade the celebrations have ensued, even since the passing of Nihat in 2009. A patient-centric advocate in the world of social media and eMarketing.

Journal For Patient Compliance Strategies to enhance Health Outcomes 61



Strategies to enhance Health Outcomes

New Catalent/SDI Study Shows Adherence Packaging Solutions Drive Substantial Gains in Patient Persistency Catalent Pharma Solutions, a leading provider of drug delivery technologies and packaging solutions, announced results of an independent study in which unit-dose patient adherence packaging was associated with a 17-point increase in patient persistency to a drug over 12 months, as compared to conventional 30-count bottle packaging.   The study utilized patient data from SDI, a leading provider of anonymous patient-based prescription data. SDI’s prescription coverage represents claims data from over 50% of the retail pharmacies in the United States. The claims from these pharmacies account for one half of dispensed claims across all pay types, including Cash, Commercial 3rd party, Medicare Part D, and Medicaid. The adherence study looked at patient persistency rates over a 12-month period by analyzing a cohort of ~200,000 qualified patients who filled their prescriptions in either a traditional bottle or a patient adherence package. Persistency rates were defined as the percentage of patients who remained compliant or restarted therapy over the 12-month tracking cycle.  “We believe that every element of dose form and package design can be selected to improve patient treatments.  Previous studies have identified packaging as one of many means to increase patient adherence, but none have focused on the impact of packaging alone,” stated Cornell Stamoran, Vice President of Strategy and Corporate Development at Catalent Pharma Solutions.  “For the first time, we have quantified the real-world patient adherence benefit that advanced drug packaging can provide.”  Unlike the conventional 30-count bottle, which is commonly used throughout North America, adherence packaging is designed with a focus on unit dosing, reminder prompting, printed instructions, timedating and other features that enable delivery of the right dose at the right time. Adherence packaging safety is enhanced through child-resistance features, and adult-friendly attributes make the package easier for patients to open.  “At Catalent, we do not believe in the concept of ‘one size fits all’ for patient adherence solutions” Mr. Stamoran commented.   By focusing efforts on a better understanding of the patient experience coupled with expertise in drug development, Catalent can look at multiple different ways to better the patient experience.  This is evident in different packaging designs or by enhancing the delivery format of the drug with an orally disintegrating tablet, such as Catalent’s Zydis® fast dissolve technology.   Ultimately, improving the patient’s experience and engagement will improve the patient’s adherence.  Through Catalent’s expertise from dose to delivery, the company can provide a tailored solution to enhance each patient’s experience. The new study results suggest that appropriately tailored packaging can provide customers with cost-effective solutions that positively impact patient adherence and treatment outcomes. Source: Chris Halling – Catalent

62 Journal For Patient Compliance Strategies to enhance Health Outcomes

JPC News

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. Community pharmacists interested in assisting (by advertising the research on A4 poster and displaying business cards on the pharmacy counter) should register their interest at http://abc., or contact: Comfort Mshelia on 01782 734794. Source: Jaypreet Dhillon, JCS Staff Reporter Joint Pharmacy And Pharma Initiative Improves Patient Adherence Rates By 20% Independent community pharmacy virtual chain Numark has worked in partnership with Pfizer -manufacturer of the smoking cessation medication ChampixTM (varenicline tartrate) - and Pfizer Healthy Partnerships, to support patients through a successful quit attempt, by delivering a patient adherence programme in the pharmacy environment. There are about 10 million adults who smoke cigarettes in Great Britain which is about a sixth of the total UK population2. 22% of adult men and 21% of adult women are smokers, but as many as two thirds of these want to quit2. This initiative is an example of what can be achieved for better patient outcomes in their quit attempt, through effective joint working. The results of this first pilot show that the interventions by community pharmacy increased adherence to Champix by 20% over the first four weeks, and showed over 50% increase in the number of prescriptions dispensed1. In addition, patients valued access to this service within a pharmacy environment: - 84% of patients rated the support programme as valuable or very valuable1 - 100% of patients rated the pharmacist’s knowledge as excellent1 - 83% would recommend the patient support programme to a friend1 When a patient presents to the pharmacy with a prescription, Volume 1 - Issue 2

the pharmacist provides face-to-face counselling on the medication. Over the course of the treatment period, the pharmacist provides regular face-to-face and telephone education. They discuss the ongoing treatment, behavioural changes and patient expectations in order to increase the probability of a successful quit attempt. Numark member, Shamir Patel of North Meols Pharmacies Ltd who was involved in the pilot says “I found this service an excellent way to engage with patients, support them with their treatment and build their loyalty to my pharmacy. The service was very easy to deliver, the data capture was done through the PMR (Patient Medication Record) system which for me working in a busy pharmacy was very important” Speaking at Numark’s international conference in Delhi, Mimi Lau, director of professional and training services, said: “We are all aware that inappropriately used medicines cost a significant proportion of the NHS budget through increased GP consultations, hospital readmissions and medicines’ wastage. It is also recognised that pharmacists could be used more effectively to improve patient adherence that will capitalise on the many benefits community pharmacists have in reaching patients.” “Crucially, the support programme is designed to not just measure adherence to medication, but also how this impacts on the health outcome for the patient, reasons for a patient discontinuing treatment and the associated NHS spend.” Jason Perfitt, Head of Customer and Channel Marketing from Pfizer UK adds: “The impact that this support programme has made to patients intending to quit, and the value that they have placed on the service provided by their pharmacist, clearly shows the need for smoking cessation support programmes in the pharmacy environment.” Source: Jaypreet Dhillon, JCS Staff Reporter 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. Haskard-Zolnierek 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. “When regimens are more complex and intrusive patients are

more prone to forget what they are supposed to do and are less likely to be able to carry out the directives that they do recall. Patients carry out prescribed regimens less effectively when they view their health problem as less severe,” the authors wrote in their paper, “Improving Patient Adherence: A Three-factor Model to Guide Practice.” Nonadherence often is unrecognized by patients and their clinicians, according to DiMatteo, the study’s lead author. “Patients often misunderstand the value of following medical recommendations accurately and physicians often overestimate patient adherence or cannot determine which patients are having adherence difficulties.” The model identifies three categories to guide providers and patients toward adherence: Information, Motivation and Strategy. • Information -- Many patients are incapable of understanding the health information they receive. Recommendation for clinicians: Communicate information effectively to patients. Build trust and encourage patients to participate in decision-making and to be partners in their own health care. Ask patients to share why and how they will carry out their treatment recommendations. Listen to patients’ concerns and give them full attention. • Motivation -- Patients only follow treatments they believe in. Motivating patients to follow treatment recommendations is important. Recommendation: Help patients to believe in the efficacy of the treatment. Elicit, listen to and discuss any negative attitudes toward treatment. Determine the role of the patient’s social system in supporting or contradicting elements of the regimen. Help the patient commit to adherence and to believe that they are capable of doing it. Be aware of and sensitive to patient’s cultural beliefs and practices, and view treatment through a cultural lens to make sure that recommendations do not conflict with cultural norms. • Strategy -- Concrete barriers represent a common set of obstacles to adherence, such as the cost of medications, unreliable transportation to make appointments, mental health issues and complex treatment regimens. Patients need a workable strategy to follow treatment recommendations. Recommendation: Help overcome practical barriers that make it difficult for patients to effectively carry out a course of action. Identify individuals who can provide concrete assistance. Identify resources to provide financial aid or discounts. Provide written instructions/reminders. Sign a behavioral contract. Offer links to support groups. Provide electronic reminders or follow-up phone calls. The IMS Model emphasizes the importance of patientpractitioner relationships for effectively informing, motivating and strategizing with patients. It also is a useful tool for targeting patient needs, focusing on elements that are essential to achieving individual patient adherence ,and ultimately optimizing health outcomes, the researchers wrote. “Nonadherence is a complex problem and addressing it requires the efforts of both patients and clinicians, as well as all members of the health care team and the individuals who are part of patients’ everyday lives,” they said. Source: Jaypreet Dhillon, JCS Staff Reporter Journal For Patient Compliance Strategies to enhance Health Outcomes 63



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