PCDD – A Roadmap

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Patient-Centered Drug DevelopmentA ROADMAP FOR PHARMACEUTICAL LEADERS

Oral Therapies in the Oncology MarketplaceGrowth Potential, Challenges and Trade-offsPatient-Centered Drug DevelopmentA ROADMAP FOR PHARMACEUTICAL LEADERS

Contents

Foreword from Andreas Koester 3

Foreword from Paulo Moreira 4

Introduction 5

Definition and measurement 6

What patients really want 8

Trial design 12

Systematic engagement of 14patient advocates

Patient-centered systems and 15trial technology

Better site management, 16clearer patient focus

The future of trial communication: 17Online, social, mobile?

Mobile trials and direct-to-patient 19(DTP) solutions

The FDA and Patient centricity: 21What are regulators doing?

Expectations and outlook 24

Conclusion 25

DISCLAIMER

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Contributors to this paper

Marc Boutin, EVP and COO, National Health Council

Bonnie Brescia, Founding Principal, BBK Worldwide

Elise Felicione, Director, Clinical Trial Innovation, Janssen

Zach Hallinan, Director, Patient Communication and Engagement, CISCRP

Andreas Koester, VP, Clinical Trial Innovation, Janssen

Greg Koski, President and Co-Founder, Alliance for Clinical Research Excellence and Safety (ACRES)

Rhonda Kost, Clinical Research Officer, The Rockefeller University Center for Clinical and Translational Science

Paulo Moreira, VP, Head of Global Clinical Operations – External Innovation, EMD Serono

Susan Sheridan, Director, Patient Engagement at the Patient-Centered Outcomes Research Institute (PCORI)

Jack Whelan, Cancer Survivor, Warrior and Patient Leader

Javier Zambrano, Director, Biogen Idec.

Joel Beetsch, VP, Patient Advocacy, Celgene

Jennifer Byrne, Chief Executive Officer, PMG

Chris Frega, Sr. Director and Head of Global Feasibility and Patient Recruitment, Quintiles

Jeremy Gilbert, VP, Product and Strategy, PatientsLikeMe

Sharon Hanlon, Director, Clinical Trial Partnerships, Bristol-Myers Squibb

Michael Jones, Sr. Director, Clinical Operations, Eli Lilly & Co

Richard Klein, Head, FDA Patient Liaison Program, Office of Health and Constituent Affairs

Paul Kluetz, Acting Deputy Office Director of the Office of Hematology and Oncology Products, FDA

Tom Krohn, Chief Development Officer, TrialReach, former Lead, Eli Lilly’s Clinical Open Innovation Team

Theresa Mullin, Director of the Office of Strategic Programs in the Center for Drug Evaluation and Research, FDA

James O’Leary, Chief Innovation Officer, Genetic Alliance

Jeanne Regnante, Head, CMO Strategy Office, Chief of Staff to the CMO, Merck

Tomasz Sablinski, Founder and CEO, Transparency Life Sciences

Roslyn Schneider, Global Patient Affairs Lead, Pfizer Sciences

Tom Sellers, Sr. Director, Patient Advocacy and Corporate Philanthropy, Takeda

Veronica Todaro, VP, National Programs, Parkinson’s Disease Foundation (PDF)

David Verbraska, VP, Worldwide Public Affairs and Policy, Pfizer

Glen de Vries, President, Medidata

Bernard Vrijens, Chief Science Officer, MWV Healthcare

David Vulcano, AVP & Responsible Executive for Clinical Research, Hospital Corporation of America

Jeff Williams, SVP Operations, Apple

Lode Dewulf, Chief Patient Officer, UCB

3www.eyeforpharma.com/clinical CONTENTS / PRINT

Foreword from our Conference Chairmen

Patient centricityNot a new concept, but an increasingly important one

Dear Colleagues,

From talking to you at conferences like eyeforpharma’s Patient-Centered Clinical Trials, I get reminded once in a while why many of us joined the life sciences field: following a deep running passion to improve and save patients’ lives. But step into any pharma or biotech company’s office and you can experience what happens to good intentions once they have to compete with the demands of tight timelines, budget pressures, and regulatory requirements. It’s easy to forget who we aspire to be working for.

But there is an obstacle to patient mindedness more insidious than just time pressure: it’s the notion that we – due to education and experience – know what patients want and need.

But when we look around us, we can see every day that this paternalistic model is falling apart. Thanks to technology and social media, patients often know as much (or more!) about their disease than their doctor.

A decade ago, it was moribund HIV patients who made their voices heard and created the impetus for pharma and regulators alike to heighten their attention towards patients’ needs. Maybe we can learn from the HIV/AIDS example and from the successful approach Genzyme and others have taken in rare diseases, when we try to find and define a new balance between scientific rigor and patient burden, between risk and benefit, between the need for confidentiality and the mandate to inform.

So, maybe the challenge ahead is not so much about reinventing new approaches, but rather harnessing the technology that is now at our disposal to incorporate what served us and our patients well in life-threatening diseases into every step of the drug development process for any and all diseases. I’m convinced if we do this consciously, forcefully, and jointly, we may look back in just a few years on 2014 and ask ourselves why it wasn’t always second nature for us to check with the very patients afflicted by the disease we are trying to cure to understand what’s important to them rather than just assuming that we know.

So let’s brainstorm together and share ideas and best practices so that we can truly deliver “the right thing to do” for our patients throughout the drug development process. And while we are at it, for those who still need a little convincing that all the investment in time and resources is necessary and worthwhile, let’s create the foundation for a business case on how engaging patients in clinical research can be a cure for many of the problems (expensive amendments, poor recruitment, high attrition) that ail the clinical research enterprise today.

Andreas KoesterVice President, Clinical Trial Innovation & External AlliancesJanssen/Johnson & Johnsoneyeforpharma PCCT Conference Chairman 2014

4www.eyeforpharma.com/clinical CONTENTS / PRINT

Patient centricityA comprehensive, holistic endeavor

Dear Colleagues,

We are living in times of unprecedented innovation in the pharmaceutical industry. In the recent past, there has been an awakening to the important role that patients can play in helping biotechnology and pharmaceutical companies develop new medicines.

Given the advent of and exponential growth of the internet, the amounts of medical information available is astronomical. Patient are more educated and better informed than they have ever been. This knowledge has given way to patients that are engaged and more vested than ever in their treatment options. The role of patient advocacy groups is also expanding in this area.

We are looking forward to acquire invaluable insights on how some collaborative models between pharmaceutical companies and patient advocacy groups are having a very positive impact in the industry.

Patient centricity in clinical trials has been interpreted and implemented in many ways. However, patient centricity cannot be viewed simply as isolated activities that aim directly at the patient. It is a much more comprehensive endeavor. Successful implementation must rely on a holistic approach that touches all of those with a vested interest in the clinical research and development enterprise.

We propose to shine a light on these complex interactions and demystify how, sponsors, patients, clinicians, patient advocacy groups, regulators, innovation and technology can come together to deliver new medicines faster to patients without compromising the scientific merit of the clinical trial.

Paulo MoreiraVice President, Head of Global Clinical Operations – External InnovationEMD Seronoeyeforpharma PCCT Conference Chairman 2015

Foreword from our Conference Chairmen

5

Introduction


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Patient centricity has become a key priority for leaders in clinical trials – but few in the industry know how to go about achieving it. Key questions remain unsatisfyingly unanswered. For example, how should we even define patient centricity? How is it measured? Where has it been successful so far? What are the challenges in coming years? Drawing on in-depth interviews with clinical leaders who participated in eyeforpharma’s Patient-Centered Clinical Trials program, this paper provides answers to these and other crucial questions, looks at solutions for change and examines those companies which are putting in place structures to make patient centricity an organizational reality.

Putting patients at the center of the trial has the potential to make the development process more effective – which makes it attractive – but it also requires a paradigm shift – which makes it difficult. Changing the role of the patient from subject to participant needs a new culture, mind-set, framework and language. While some observers use the term “baby steps” to describe where the industry presently stands on patient-centered drug development, the case studies and examples in this paper indicate that more sophisticated, long-term strategies are now being designed.

“Product development with the help of end users is common in industries such as the automobile or food industry – it is only relatively new to pharma.”

Paulo Moreira Vice President – GCO Head of External Innovation, EMD Serono

Ignoring the patient means that critical insights are missed by all stakeholders. “Historically, patients have not played a significant role in determining the research questions or the outcomes that really matter to patients,” says Susan Sheridan, Director of Patient Engagement at the Patient-Centered Outcomes Research Institute (PCORI). “I think it has been assumed that this is only researchers’ territory and that it is too complex.”A recent poll by PatientsLikeMe among 70 clinical operations leaders at the Avoca Quality Consortium, points to the dominant thinking: Patients are viewed as having too little ‘expertise and capabilities’ to be able to really contribute.

A rethink is now a matter of urgency for everyone involved. “Today, trials are complex, where millions of dollars rest on patients’ reactions to a trial protocol and how quickly they can link to the trial and potentially enroll,” says Jeremy Gilbert, VP, Product and Strategy, PatientsLikeMe. “Despite that, clinical teams spend months trying to ‘think like a patient’ in making protocol trade-offs but they rarely actually ask the patient or study the patient’s own perspective.” These approaches typically focus on medical outcomes, which don’t capture the journey the patient takes en route – involving aspirations for their personal life, treatment and recovery.

R&D costs have “spiralled out of control”,says Michael Jones, Senior Director, Clinical Operations, Eli Lilly & Co.

“Focus on the patients can help us to focus on the questions that matter most. We can streamline the research by focusing on the patient,” he suggests.

There are some interesting current examples of a practical move towards patient-centered drug development, such as Janssen’s MyCentralCare (read more in our section on patient-centered systems below). But Elise Felicione, Director, Clinical Trial Innovation at Janssen R&D, warns that there is no quick fix: “Don’t think that it will be three months from talking about this to patients actually using your portal.”

“Patient centricity is not doing the same non-patient-centric things but with the addition of a graphic from management, containing a bunch of call-out boxes, emanating from a diagram of a patient in the middle.”

David Vulcano AVP & Responsible Executive for Clinical Research, Hospital Corporation of America

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Definition and measurement

All stakeholders – including patients, HCPs, pharma, regulators, HTAs, payers, and politicians – accept that more patient involvement in drug development is needed although there is no widely accepted standard for what constitutes patient centricity. While our interviews revealed various definitions of the term, there are clear areas of consensus.

It may initially be helpful to define what patient centricity is not. According to David Vulcano, AVP & Responsible Executive for Clinical Research, Hospital Corporation of America, the main reason why patients are often ignored in drug development is “because we’re trying to do everything the same for all the other stakeholders and then add patient centricity in to the mix”. He goes on:

“I see a lot of these slides from multitudes of sponsoring companies and CROs but not a lot of action here with the exception of trying to be more creative in recruitment and retention and calling that ‘patient-centric’.” Vulcano’s point is clear: Anyone who thinks that simply talking about patient centricity is enough needs to think again.

So what is it? “In its purest form, patient centricity is the creation of a direct link between the goals of clinical trials and the needs of patients on an individual and global scale,” says James C. O’Leary, Chief Innovation Officer at Genetic Alliance. “It is not simply designing trials to meet the needs of participants, but rather creating systems and tools that allow participants to inform and influence the trials themselves.” Jeremy Gilbert, VP, Product and Strategy at PatientsLikeMe, has a similar definition:

“Measuring what matters to the patient in the trial itself, and designing the trial as much as possible to accommodate the impact on the patient’s life.” Roslyn F. Schneider, Global Patient Affairs Lead at Pfizer, thinks it is helpful to concentrate on three main areas:

• Meaningful involvement, including more direct patient input at key points such as trial protocols

• Patients receiving data where they need it, in a manner they can easily interpret to actually improve their health

• Utilizing technology to bring patients closer to what the industry is doing.

Rhonda Kost, Clinical Research Officer, The Rockefeller University Center for Clinical and Translational Science adds that patients’ priorities such as convenience, expense, pain, risk, and benefit must be taken into account, while Bonnie Brescia, Founding Principal at BBK Worldwide, sums it up as “making sure you’ve included the voice and values of the participant”.

CORE GOALS OF PATIENT CENTRICITY IN DRUG DEVELOPMENT

• Meaningful inclusion of patients, in particular for trial protocol design

• Linking needs of patients with goals of clinical trials

• Considering patients’ experience of their disease throughout the program

• Taking patient priorities such as convenience, pain, expense and benefit into account

• Measuring what matters to the patient

• Giving patients appropriate, timely and user-friendly information

• Using technology to include patients more

• Including voice and values of patients

It is one thing to agree on the tenets of patient centricity in clinical trials, but it is another thing entirely to measure the concept.“ A barrier to metrics at the moment is that most people don’t know what we’re trying to measure,” explains Schneider. “To show it is meaningful, and to test different models, we need to be able to measure it. Patient satisfaction alone is important but is not the only answer.”

Soft measures of patient centricity such as the level of trust that a patient has in a trial or a company are easy to pinpoint, says Tomasz Sablinski, Founder and CEO of Transparency Life Sciences. “Once the trial has started we can measure how many are adherent to the trial protocol,” he adds. “Just the willingness to participate is an important measure, and how many are willing to inform their fellow patients about a trial.”

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Definition and measurement

EMD Serono is establishing patient advisory boards to include the ‘patient voice’ while most sponsors use some form of patient survey to capture perceptions of informed consent procedures, trust, feeling of partnership, unexpected pain, convenience, feeling of respect, sense of being listened to, and overall experience. Michael Jones, Senior Director of Clinical Operations at Eli Lilly & Co, has used such feedback mechanisms to identify opportunities to improve. Eli Lilly sought answers to the common questions: “Are we able to shorten recruitment cycles? Can we better retain patients?”

But since clinical leaders have only recently started to fully embrace a patient-centered approach, more structured metrics simply do not yet exist – something particularly true of return on investment (ROI) measurements. “It is difficult to quantify because each protocol is unique,” says Paulo Moreira, VP and Global Clinical Operations Head of External Innovation at EMD Serono. “You would need to focus on historical accrual rates, number of patients per site per month, etc. Then, calculate how much faster it was done under the new model of patient centricity and assign a price to it.”

Brescia of BBK believes that the question – “what’s the ROI on being patient-centric?” – is the wrong one to ask anyway.

“I’m concerned about linking the two together – patient centricity is either a moral imperative or it isn’t,” she states. But even if cost saving is not the primary issue, proper management of patient centricity in clinical trials still depends on valid and reliable measurement – indicators such as recruitment and retention could fulfill this role.

“In some companies, to get a protocol approved internally, teams must demonstrate what steps they have taken in

protocol design to incorporate the patient voice – and then show what aspects of the design have been influenced by their efforts,” Brescia continues. “If you’re talking about measuring the ROI of a strategic means to accelerate drug development, then that’s the patient recruitment discipline. Recruitment and retention can and should be measured against ROI; they are two key drivers of research success and an indication that you have done a good job of partnering with patients. Patient centricity is demonstrated by your actions and your ability to improve relations with individuals.”

“Patient centricity is demonstrated by your actions and your ability to improve relations with individuals.”

Bonnie Brescia Founding Principal BBK Worldwide

Looking to the future, companies should be able to document the impact of patient centricity in areas like study design, outreach materials and site performance against historical trends or a benchmark. This needs to happen, says Vulcano, because pharma has at some point to prove patient centricity’s value to the healthcare ecosystem.

“If value can’t be proven, then it is just the latest buzzword in a competitive public relations stalemate,” he concludes.

“I say ‘stalemate’ as I have never seen a company out there (and don’t expect to see one) saying they don’t put the patient first.”

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What patients really want

The most important question is, of course, understanding what patients actually expect to get out of their participation in clinical research – and the Patient-Centered Outcomes Research Institute (PCORI) is pulling together a database which will help pharma understand just this.

“Patients and researchers are helping us to build this Engagement rubric almost like Wikipedia,” says Susan Sheridan, PCORI’s Director of Patient Engagement. “It’s a framework for innovation and a sort of crowdsourcing of engagement activities by the patient and researcher community in our funded portfolio. We plan to evolve this framework continually, based on examples from the field in the future.”

“Patients are eager to hear about research opportunities, but they do not want to be infantilized or subordinated. They want to be afforded the respect to make their own research participation decision.”

Rhonda Kost Clinical Research Officer, Rockefeller University Center for Clinical and Translational Science

One of the principles in the PCORI rubric focuses on disruption to patients’ lives. “We want the research and the research setting itself to be patient-friendly,” Sheridan goes on. “For instance, with the community of those with physical disabilities, research should be located next to appropriate transport facilities, be accessible or use technology to reduce travel requirements. For a trial involving Latina women it should all be translated into Spanish. I think patients will be more demanding about trials being disruptive to enhance recruitment.”

Part of the problem has been that moves to improve recruitment for clinical trials have long been limited to urging doctors to pitch research studies to their patients and to refer patients to the studies – and this approach has not worked, says Rhonda Kost of Rockefeller University.

“Only patients, and participants, can tell us what draws them to, or repels them from research participation,” she says,

suggesting that the first step in the development of that partnership is to ask the patient or participant what they value about the research experience. “Patients are eager to hear about research opportunities, but they do not want to be infantilized or subordinated,” Kost insists. “They want to be afforded the respect to make their own research participation decision, starting from how they hear about research.”

MOTIVATIONS BEHIND CLINICAL RESEARCH PARTICIPATION

Individual patients have various motivations for getting involved, and understanding these will bring pharma closer to achieving the optimization of trial processes, budgets, and timelines. At the core, patients want improved treatment prospects – but it is also very important to bear in mind less tangible feelings. They can include hope (for their future and that of their families), altruism (patients want to help fellow sufferers) and practical considerations (such as trial duration and convenience, site accessibility, and transportation needs) which may not be top of the list of concerns for sponsors but are vital for patients. The invasiveness or pain of a treatment in the trial, as well as nature of the disease also have significant implications for the success of the process.

Do trial participants find the interaction with trial investigators burdensome? PMG Research, a site management organization, recently facilitated a patient panel for one of its key pharma partners.“You might find this surprising,” says Jennifer Byrne, PMG’s Chief Executive Officer. “When asked about initiatives and technology that might lessen the burden of coming on site, overwhelmingly, the clinical trial participants expressed that they value the direct contact with physicians and study staff and see this as one of the greatest benefits of trial participation.”

Chris Frega, Senior Director and Head of Global Feasibility and Patient Recruitment, Quintiles, also reports that gradual progress is being made.“We are increasingly able to incorporate the patient voice,” he argues. “We have seen some great results through additional input into protocol

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development, understanding if patients will actually accept the design and what their specific motivations may be, and balancing the views of other experts like investigators, KOLs, sponsors.”

As part of the Patient-Focused Medicines Development (PFMD), a new initiative to find common ground between all stakeholders, Roslyn F. Schneider, Global Patient Affairs Lead at Pfizer, is one of those pharma industry stakeholders currently developing what patient-centric models should look like. Schneider advocates for a collaborative approach as companies test their models.

“Patients can tell us about their experiences – they are the experts,” she says. “But they may need a certain amount of training – for example, on CT protocols – to know what we’re talking about when it comes to feasibility, and agreements to protect IP and confidentiality in the context of drug development.”

The priority over the next couple of years must be to develop the framework that identifies where patients can be plugged into the process in a meaningful way, to ensure that they are not merely token participants. “We also need to ensure that this extends to a diverse patient population, including those from under-served communities, and those from different ethnic and racial backgrounds,” PCORI’s Sheridan adds.

“And we need to measure and evaluate how patients are making a difference in research. PCORI has created the WE-ENACT tool to evaluate the engagement in our projects.”

In resource-constrained times, pharma has to figure out how to become truly patient-centric in a way that is completely compliant and efficient, thinks Schneider. But while Pfizer believes it will ultimately produce more revenue as well as better health, the process of getting to that point cannot reduce access or slow down the timeline. “That would be unacceptable,” she insists.

CASE STUDY: PFMD WORKING GROUP

Patient-Focused Medicines Development(PFMD): a cross-industry initiative

Getting better patient engagement across the pharma continuum is the raison d’etre of a new working group called Patient-Focused Medicines Development (PFMD), a partnership between pharma and patients seeking to share ideas and best practice.

It brings together stakeholders across the space via workshops and meetings in a bid to establish a

“master framework”, setting out how systematic patient involvement covering the entire medicines lifecycle would work. The group’s vision is that medicines will “deliver more relevant and impactful patient outcomes by addressing unmet patient needs, and medicine development is faster, more efficient and more productive”. Currently involving four patient representatives (two EU and two US), five sponsor companies and one independent expert, the informal group focuses on North America and Europe but insists it has “global intent” and is open to more members.

PFMD membership

James Anderson GSK

Angelika Joos Merck/MSD

Marc Boutin US National Health Council

Peter Verdru UCB

Lode Dewulf UCB

Jeanne Regnante Merck/MSD

Jan Geissler EUPATI

Roslyn Schneider Pfizer

Anton Hoos M4P (Medicines4Patients) Consulting

Murray Stewart GSK

Diana Hughes Pfizer

Veronica Todaro US Patient Leadership Council

Graeme Johnston UK RA Patient

Gervais Tougas Novartis

“It is a think-tank of like-minded individuals from across the biopharma eco-system,” explains Jeanne Regnante, Head of CMO Strategy Office, Chief of Staff to the CMO at Merck.

“We got together to understand the landscape, problems, best practice, and to chart a course for the future.” >

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The idea grew out of a CMO roundtable but, crucially, there was early agreement that discussion should not take place about patient centricity unless patients themselves were in the room. “You all start to have opinions about how to do this,” Regnante goes on. “It’s important to share perspectives and opinions – we’ll be better together.” The ultimate aim is helping to create, via a more efficient development process, medicines which work better for patients.

“You need to bring multiple stakeholders together and have a conversation around patient engagement,” agrees fellow PFMD member Marc M. Boutin, Executive Vice President and Chief Operating Officer, National Health Council. “How else do we get to a place where it works for everyone? Collaboration is focused on interdependence, trying to understand how we’re all successful in achieving our aims.”

To make all this work, PFMD will have to formalize a consistent approach to patient centricity and help shape the environment externally so this approach in turn becomes the norm. The challenge will be distilling the range of perspectives from individual patients, patient advocate groups, pharma companies – and different departments within them – as well as regulators. “Perspectives may be different,” he continues. “Shared definition becomes a starting point.”

Schneider acknowledges that the informal partnership has to come up with substantial ideas. “We need to work together across industry groups and patient groups to develop a framework to include what’s being done already and give structure that we could all build on,” she says. “We can’t expect others to embrace and implement it if we wouldn’t commit to that.”

The need to tackle this issue is apparent because corporate boilerplate statements are given little credence by the public – and perhaps even from within their own organizations. A recent eyeforpharma survey asked industry executives globally who was spearheading the concept of patient centricity in their company. 20% said it came from the board, others said it came from the CMO – but 17% admitted that no one leads the initiative. “One of the barriers is that companies think there’s a law against doing it,” says Regnante. “But we can do it through patient organizations and academia. So the challenge is cultural, but also finding sponsorship within a company is critically important to achieve innovation. Cultural change can happen but you need champions inside.”

One of the biggest challenges around clinical trials is that they have been designed by researchers mostly removed from medical management who are using them as an opportunity to get every possible bit of information Boutin suggests. While that is understandable, it makes things arduous for the patient, does nothing for retention and means there is work to be done in weeding out the protocols that are not useful at all. “We’re constantly having to calibrate what we do,” he says. “You’ve got to be vigilant to get the right balance.”

Issues that are being considered within PFMD at present include what approaches have been most influential in transforming the ways trials are designed and various different examples of involving target groups in this activity. “Getting patient input should be done in a variety of ways – we should start now and not wait for

‘perfect’,” insists Regnante. “We are focusing on sharing best practice and there’s probably ten ways of doing it. The field is wide open.” >

CASE STUDY: PFMD WORKING GROUP continued…

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Exchanges must be bi-directional, so any microsite designed to help patients and caregivers must be user-friendly. “The industry of yesteryear might have asked physicians what they thought or used our own subject matter expertise,” she goes on. “But we’re really thinking about all different aspects of how we engage with stakeholders. This is all about patients who are suffering every day and want solutions to help them and their families. If they were to say that their engagement has been valuable then we will have succeeded.”

While the importance of face-to-face interaction is understood, technology is still likely to be a driver for patient-centricy, and Schneider expects these issues to be addressed by PFMD more as the group develops a framework. “Technology will be critically important depending on the type of methodology,” Boutin says.

“But the methods will have to be aligned to the questions and responses that you want to receive.”

As things open up, Regnante believes social media may be useful some way down the line, for example, but says there needs to be more one-on-one interaction in these

early stages. “We need to do a better job of garnering trust,” she says. “We need to start the relationship – I think we’ll get there in terms of social media but this is a new relationship and it’s better to talk face-to-face initially.”

PFMD’s members believe trial design is beginning to change for the better and the emphasis is shifting from scientific decisions being made about patients towards issues of judgment about clinical effectiveness with patients’ input. “This will lead to much higher value products coming out of the pipeline if we do this right,” Boutin enthuses.

“You look at how patient engagement is transforming biopharma, this momentum is becoming embedded and will spread into delivery models, quality measures, and reimbursement activities to create new health models. And I think this will come together in a really nice eco-system in the next 7-10 years.”

Yet despite all the optimism, no-one in PFMD is under any illusion about the amount of work to be done. “Resistance to any change is endemic,” he says. “In all of society”.

CASE STUDY: PFMD WORKING GROUP continued…

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Patient-centered trials will require new processes to involve patients in formulating research questions, study design, trial conduct and disseminating study results, changes that will we need to be managed in tandem with clinical needs.“Trials are becoming increasingly complex,” cautions Chris Frega of Quintiles. “However, as an industry we need to strive to better balance the complexity and scientific/data needs with the ability to actually conduct studies and enroll patients in them in the least invasive way possible.”

Trials also have to measure outcomes that patients care about, says Tomasz Sablinski, Founder and CEO of Transparency Life Sciences, and they should do it in a way that is least intrusive to patients’ daily lives. “If you can accomplish both of those things it’s going to be a quantum leap compared with where we are today,” he suggests.

“We’ve designed seven or eight different protocols: four are recruiting or are about to recruit patients. We’ve made several changes to clinical study protocols, several suggested by patients. Our trial in multiple sclerosis is based on patients’ feedback – as a result we incorporated several new tele-monitoring devices into the trial.” But combining these priorities doesn’t need to require increased complexity; in contrast it could lead to simplification, says Paulo Moreira of EMD Serono. “A comprehensive model of patient centricity will lead to reduced timelines and costs associated with developing a new drug,” he says.

Pharma companies will also need to be increasingly flexible in their study plans, and open to perpetual change.

“They could pick two or three ideas such as including patients in protocol planning and design, implementing study visit run-throughs, and sharing study results with patients,” says Bonnie Brescia of BBK Worldwide.

Part of the problem, some experts think, has been that what is required from studies has also shifted away from patient needs. Rhonda Kost, Clinical Research Officer at the Rockefeller University Center for Clinical and Translational Science, has been

frustrated at the “steady increase” in regulatory and educational requirements for investigators. Heavy on theoretical input for human protections, without any outcome measures from the true user of those human subject protections – the participant. “How could we know if consent was truly informed if we didn’t ask the participant how their experience compared with what they had been prepared for?” she asks.

The issue of consent is at the heart of making it easier for patients to become involved in trials in the first place. At eyeforpharma’s 2014 Patient-Centered Trials Conference, Tom Krohn, then Business Lead of Eli Lilly’s Clinical Open Innovation Team outlined a new approach. According to Krohn, the main problem has been that the industry makes only incremental improvements in this area. “We build on the same paradigm over and over,” he says. “We haven’t thought about the paradigm differently in the consent process.”

Trial design

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Trial design

Krohn suggests de-coupling “informed” and “consent” to create a new frame of reference for working with patients. The consent process flows out of the clinical study design protocol, where at present the patient is typically out on the margins. “They have a real challenge at finding and understanding what we’re doing,” says Krohn. “We’ve made it difficult for them, partly because it’s a closed model and also because of how we engage them.” Krohn suggests making clinical trial information easy to access online, in the same way that flight or hotel information has evolved. You would show patients the entire schedule – for example, is it one lumbar puncture or three, does a patient have to bring their mom because they’re going to be knocked out – in advance of a site visit, rather than the patient having to make a 200-mile trip to get the document “because we’ve coupled ‘informed’ to ‘consent’. If pharma does not answer these practical questions upfront, then patients will not understand studies any better. Krohn notes that “Patients’ questions and language are very different to ours,” and pharma must make the effort communicate to patient’s priorities, not their own.

Following on from that, the industry needs to think about how it can change these points of consent into points of engagement, says James O’Leary, Chief Innovation Officer at Genetic Alliance. There are 7,000 diseases and an infinite number of research questions that could be used to engage patients – but pharma has too narrow a perspective here.

“We view things differently to real people,” he continues. “They say: ‘What do I need for me and my family?’ One of the major missed opportunities in clinical trials is our inability or unwillingness to allow individuals to use their data effectively, both in enrolling in trials and using the data generated to improve their health and contribute to research.”

In a project called PEER (Platform for Engaging Everyone Responsibly), Genetic Alliance has partnered with Private Access, a firm which specializes in participant-centric access controls and privacy management systems. “Using a technology called Privacy Layer, this partnership places a user-controlled key in-between individuals’ data and potential users of that data,” O’Leary explains. “By giving participants the ability to activate and share their data, personalized connections are made and research is accelerated.” This means PEER is essentially a registry system that looks at things in a different way, putting control in the hands of people who can set their own data sharing and privacy settings. Conversion rates have been promising in people who click through in this community, O’Leary says. “This is something people want,” he concludes. “They are interested in engaging with it.”

Ensuring that patients adhere to their treatments must also be built in to trial design – otherwise the consequences can be catastrophic. Bernard Vrijens, Chief Science Officer, MWV Healthcare and Adjunct Professor of Biostatistics at the University of Liège warns that poor adherence can lead to “underestimated efficacy of new drugs to the point of trial failure, underestimated incidence of adverse effects, distorted pharma co-economic analyses, and/or overestimated dosing requirements for marketed pharmaceutical.” Vrijen and his team have documented the prevalence of major shortfalls in drug exposure during clinical trials, something industry must change.“This situation is no longer sustainable under the current overall financial pressures on healthcare,” he says.

He suggests electronic compilation of drug dosing history data is required, and is convinced that smart packages – which automatically record every time a patient takes a dose out of the pack – must soon play a central role in trials.

“They provide the means to manage patient adherence and also enable analyses stratified by reliable measurements of drug exposure,” Vrijens says. The smart packs record the time of each package-opening – and are simpler, cheaper and less intrusive than smart pills.

This innovation has demonstrated success too: Vrijens has been closely involved in the development programs for new all-oral HCV treatments and says that electronic measurement of patient adherence to those treatments has led to a 97% cure rate – “a level of success that can only be achieved with almost perfect adherence”.

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Systematic engagement of patient advocates

The preceding discussion has underlined the importance of involving the patient, however patient groups have long complained that their voices are not heard enough throughout the clinical trial process. “Many patient groups have voiced that they are often only approached post-research to help disseminate research findings, but patients are now calling for greater involvement throughout the process not just after research is complete,” says Susan Sheridan, Director, Patient Engagement, Patient-Centered Outcomes Research Institute (PCORI). “Patient advocates really have a role reshaping the research to reflect what’s really important to these groups.”

Joel Beetsch, Vice President of Patient Advocacy, Celgene argues that pharma is perfectly capable of getting patients into two-way communication, fostering successful partnerships from research design and protocol development onwards. Beetsch states, “Patients and patient advocates can get involved as part of patient-reported outcome development and selection, and they can be involved in trial results interpretation across all phases of a trial,” he says.

Pharma’s benefits should be clear: involving patients in the design and conduct of research means the research can be more patient-centered, useful, and relevant. It will also establish trust and a sense of legitimacy in the findings and make more likely the successful use and uptake of research results by the patient community. PCORI has attempted to achieve this through its Patient-Centered Clinical Research Network Program, a large, representative, national network with a focus on conducting comparative effectiveness research (CER).

As the opportunities for patient advocacy groups are changing, their role and structure is adapting too. Early patient advocacy groups worked to protect patients from over-reach by drug developers, says Bonnie Brescia, Founding Principal, BBK Worldwide. “What’s happening now

is that these groups are being supplemented by more disease-specific organizations looking to have their own voices heard,” she goes on. “There are a number of organizations looking to develop expertise within patient communities, giving patients a stronger training and background on things like ‘what is drug research?’, an understanding of the differences between Phase II and Phase III and so on. Patient advocacy in clinical research is becoming a specific sub-specialty within these groups.”

“There are several ideal roles for patient advocates. Legislative advocates are perhaps the most effective voice to help educate lawmakers about the need to update out-of-date regulations.”

Jack Whelan Cancer survivor, warrior and patient leader

These changes in the role of advocacy are also reflective of the fact that patients themselves do not come ‘one size fits all’. “There are several ideal roles for patient advocates because there are several types of patient advocates,” says patient leader Jack Whelan. “Legislative advocates are perhaps the most effective voice to help educate lawmakers about the need to update out-of-date regulations.” They can also influence government on funding to support clinical research, he adds, while research advocates – patients who work on behalf of biopharma firms, for instance – also help educate physicians about what treatment options are available in trials. “These physicians are the first contact for most patients,” says Whelan. “Very few participate in research because they are not asked about it.”

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CASE STUDY: ELI LILLY’S COLAB

Eli Lilly & Co’s CoLAB initiative is a study design platform and process which Lilly hopes will make its programs more patient centric, says Tom Krohn, when speaking as Business Lead of Lilly Clinical Open Innovation Team.

“CoLAB is a dress rehearsal of a study,” he explains. “What would it be like to execute it? There isn’t a site I have visited that didn’t say ‘I wish we can be more involved in study design’. If we did that right, we have less rework, fewer amendments, and the patients’ experience would be better.” Through CoLAB, the company has in effect made trials part of a digital design process, allowing investigators to do scenario analysis – from a patient burden, cost and time perspective, for example. “One of the things we’re trying to do in complexity management is to make it real-time, fast, easy,” says Krohn.

Lilly takes a draft study design from its digital canvas and puts it into an internal collaboration platform such as SharePoint in order to open it up to various stakeholders such as study teams and sites. These come together in virtual ‘jam’ sessions. “It’s about enabling people to have a different type of conversation,” he says. The idea is to begin discussions about the protocol, such as whether the schedule of events works or if there are eligibility issues in a specific country, with the CoLAB initiative bringing study coordinators, investigators, patients and clinical staff into the process. Scientific perspectives are clearly important, but then so are operational ones. “It’s not that the sites can’t follow protocols,” says Krohn. “It’s just that we make them too complicated.” The purpose of CoLAB is to iron out the kinks, avoiding late amendments, allowing teams to flag up concerns about dosing or screening and so on, and challenging assumptions. Scenario analyses just take minutes, with CoLAB enabling teams to physically simulate the space so that it will be possible to see what it is going to be like when you enter the clinic.

Lilly measures whether participants found it useful to be involved in CoLAB and seeks to establish if sites gain the ability to execute studies better and improve engagement levels. “We find many things that we assumed were fine but were not,” Krohn says. “You end up with a bunch of protocol improvements and adjustments.” The results have been impressive: Lilly has made 189 protocol changes via simulation prior to eight studies – all because it put “the right people in the room”.



Patient-centered systems and trial technology

Not every patient group is representative of all patients’ needs and desires – however not all pharma companies are at present set up in a way which makes engagement with individual patients a viable alternative. One industry initiative that is making patient-centered trial management more of a reality is Eli Lilly & Co’s CoLAB.

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Better site management, clearer patient focus

Talking about the patient focus, a large part of the success depends on the trial sites themselves. Strategic partnerships can enhance operational oversight, drive efficiencies and speed up the resolution of issues between sponsors and sites. “We need to help sites engage effectively with potential subjects, supporting sites with methods, tools and materials for easily uncovering and answering patient resistance to enrollment,” says Greg Koski, President and Co-Founder, Alliance for Clinical Research Excellence and Safety (ACRES). “This, combined with integrating electronic health records and trials databases, more effectively applying geographic information systems and creating a global network of sites of excellence, will result in a much more effective approach to patient recruitment, retention and overall conduct of clinical trials.”

However, moves towards greater patient centricity are likely to see traditional roles changing. Will there be a role for clinical trial sites in an era of ‘direct-to-patient’ efforts?

“There are going to be some forms of research that lend themselves to direct-to-patient,” explains Michael Jones, Senior Director, Clinical Operations, Eli Lilly & Co. “Other types of studies will continue to require participation of a healthcare practitioner. We are not setting out to expressly disintermediate the trial sites. Our aim is to relieve the burden. I see that there will be a spectrum of opportunities to remove that burden and increase convenience for the patient and the site.”

In order to do so Sharon Hanlon, Director of Clinical Trial Partnerships at Bristol-Myers Squibb, says it is important to identify steps to establish a reliable, collaborative system of sharing metrics. These would monitor start-up and enrollment activities as well as site-patient relationships, tapping into the potential of patient advocacy involvement to support and enhance site relationship management.

“The sites are our key collaborators,” she says of her work developing the relationship between BMS and its sites.

The company wanted to ensure it had adequate criteria to evaluate unique skills and talents that sites have, as well as to identify future partners. The ability to sit down with site representatives and talk about issues such as electronic medical records, resources, and changes in development plans is key – but the most important thing is to have core sets of metrics on performance and quality that can be used.

BMS set up research advisory councils, bringing sites together to look at what they are doing and how they could better help patients. These councils found that sponsors tended to want to improve the start-up experience and increase access while sites wanted awareness of what is coming – something better collaboration would help with.

“They see our book of work from the time that it’s internally approved,” says Hanlon. This gives them the opportunity to input into the design of study, with teleconferences set up with KOLs at sites on issues of recruitment and so on.

She adds that having a single point of contact has made a significant difference to the relationship, allowing her to partner with sites more effectively on improvement. One site which had an average 18-month start-up time has now trimmed its processes with BMS’s help and is down to an average three-month lead time. “They’ve been the best recruiter in some of our studies,” says Hanlon.

The message is clear: with effective management, sites can improve their performance. Hanlon and the sites put together five different criteria and success factors to be judged by qualitative and quantitative measures:

• Strategic alignment• Operational excellence• Resources• Information technology• Process compatibility

Increased transparency and frequency of communication between site and sponsor can help identify potential new areas of collaboration based on joint interest and capability, as well as the implementation of process improvements based on performance measures and qualitative feedback.

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Better site management, clearer patient focus

“It has been a huge learning experience, listening to the sites,” she goes on. And it has led to real changes: following input from various teams, BMS has been able to alter its SOPs to increase the number of satellite sites it could use, an example of the sorts of broader benefits that the collaboration has brought, outside of simply leveraging synergies in the trial process.

The collaboration has also been leveraged to build connections with site-specific advocacy organizations, health equity/

disparity groups and to gain the patient perspective. There has also been increased awareness of processes with the opportunity to standardize – creating standard pre-filled documents, for instance – and a positive trend toward meaningful improvements in key study milestones. “Since the partnership, one institution has tripled number of activated studies,” Hanlon points out. “The access to health equity, minority populations associated with some of these sites have really been a meaningful difference and have really helped us in the long run.”

“We need to start the relationship with patients. We’ll get there in terms of social media but this is a new relationship and it’s crucial to talk face-to-face initially.”

Jeanne Regnante Head of CMO Strategy Office, Chief of Staff to the CMO, Merck

For pharma, building a network with influencers using online channels is one thing, but getting insights back from patients via social media is quite another. Companies worry this could lead to patients sharing symptoms or speculating over the treatment assignment and are concerned about unsolicited safety reporting and privacy violations.

But engaging patients in non-traditional ways is important as they increasingly use the internet to communicate and to become better informed. Susan Sheridan, Director, Patient Engagement, Patient-Centered Outcomes Research Institute (PCORI), says patient recruiting via social media and patient groups crafting their own privacy and data-sharing agreements are both already happening.

“A really simple but important initiative is where a patient group has rewritten a consent form in collaboration with a patient group in the UK to make it understandable and patient friendly, and is now recruiting via Facebook in both countries,” Sheridan explains. “There are also examples of patient groups suggesting the use of cell phone technology to report patient reported outcomes and for research interventions; there are many examples of patients changing or being the source of the research questions, such as a research question that was identified by an adolescent with diabetes. We’re seeing some interesting shifts: for instance, in one research program patients shortened a survey tool developed by a research team; it originally included 22 items and took 45 minutes to complete but with patient intervention the tool now has 15 items and takes 20-25 minutes.”

“The risk of sharing is sharing – but the benefit of sharing is sharing too!”

Roslyn F. Schneider Global Patient Affairs Lead Pfizer

Use of social media throws up real regulatory problems for pharma – but there also ingrained cultural barriers to overcome.

The future of trial communication:Online, social, mobile?

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CASE STUDY: JANSSEN’S MYCENTRALCARE

“The point is: let’s start talking about it, because it’s going to happen whether we want it to or not.”

Elise Felicione Director, Clinical Trial Innovation Janssen R&D

Janssen’s MyCentralCare is a secure, private online resource to support patients in a Janssen study on obesity in the US. The idea behind the portal is to help patients easily find information, and it includes FAQs and a study schedule. It explains to a patient what visits have been completed, what is upcoming, study procedures and requirements (for example, do they need to fast in advance), a link to Google maps so they can plan directions and the opportunity to sign up to visit reminders via text or email. It means that patients can go online rather than calling the site and Janssen hopes that it will improve understanding of process in general – allowing patients to bring up the site on a tablet, for instance, when discussing their treatment with family or carers.

Elise Felicione, Director, Clinical Trial Innovation, Janssen R&D, oversaw the project and states that the objective was to put the patient first at the beginning of the design procedures. Felicione says, “We brainstormed what we could do to make our studies more patient centric.” In 2013, the company actually piloted the new scheme as part of a short clinical trial. There were pros and cons: as Janssen developed this internally it was cheap to run and they had complete control over the system – but the burden of ownership meant that further implementations had to be

resourced by the company alone. Most Institutional Review Boards (IRB) approved it without making any changes, which was positive and showed the value of good preparation – but the project was dependent on the trial timelines. These were delayed, which meant the pilot itself also fell behind schedule, by a total of nine months.

The company learned above all that patient-facing innovation takes time, with adequate build-in required for stakeholder review and approval. Janssen still plans to make this a global tool, perhaps with a multi-language, multi-country website with a web or mobile app. Including dynamic content means on-going approvals are required but this also creates the possibility to expand the scope post-trial, through sharing a study results summary and invitations to join an alumni community. Felicione believes that this feature brings pharma to the next logical step for patient centricity: to facilitate patient-to-patient communication – something she argues can no longer be ignored (see Social media below).

“The first step is to start the conversation,” Felicione suggests. “If we’re not talking about it, we’re sticking our heads in the sand.” This could be disastrous, since patients are communicating anyway, leaving the conditions

“ripe for a perfect storm”. Patients have no malicious intent, she says, they just want their study to succeed.

Pharma should consider educational content about the dangers of sharing too much or too broadly, patient-authored articles, ‘letters to the editor’ or hosting a closed and moderated patient discussion forum on Facebook. The chances are there will be at least one patient who will tweet or blog about their involvement, so pharma might be better off embracing this, saying that if patients have something to share then why not pass it on to the sponsor or to the IRB for review before posting it on the site. “The point is: let’s start talking about it because it’s going to happen whether we want it to or not,” Felicione concludes.



“The key is to put some organization around something that is meant to be disorganized,” says Roslyn F. Schneider, Global Patient Affairs Lead at Pfizer. “The risk of sharing is sharing – but the benefit of sharing is sharing too! The reluctance from pharma is not because pharma doesn’t think it’s a good thing to do– but we’re still a science-based industry and we have to ensure that our engagement is scientific and has a methodology to it.”

Whatever the barriers, Chris Frega of Quintiles thinks that technologies to share what is happening and keep patients engaged in a trial have a place. “These can be social media, online communities and some that are more study specific,” he suggests. “By building communities of patients who are engaged in their own treatments, they can more easily be informed of their options should studies be initiated.”

The future of trial communication: online, social, mobile?

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Mobile trials and direct-to-patient solutions

The extraordinary potential of mobile health has only recently begun to be exploited by clinical trial sponsors. Traditional methods of executing clinical trials could be thrown out with the proverbial bathwater if the pharmaceutical industry can get to trips with the myriad of possibilities that utilise mobile technology.

Sensor technology has exploded in recent years, and the options provided, in the form of wearables, smartphones and remote devices, coupled with powerful apps and pervasive wireless access, means that direct-to-patient (DTP) solutions are already available.

Yet challenges obviously exist in terms of integrating these solutions into the current clinical trial set-up. Instrumenting patients with wearable technology has the power to transform clinical trials, but pitfalls exist in terms of potential errors. These include:

• Device failure• User error• Privacy/security• Data integration• Regulatory compliance• Site preparedness• Introduction of bias• Poor quality data

Scaling represents another challenge. For example, a recent mHealth initiative generated 18 million data points per patient per day. Managing data volumes on this scale brings its own set of difficulties.

The ubiquitous providers of mobile technology, Apple, have now made a new foray into health. They recently unveiled a new API called Research Kit, built as an open source framework and designed to help medical researchers collect data from research subjects. The new framework was co-developed by Apple and a group of renowned academic institutions including Stanford University, Massachusetts General Hospital, Dana Farber Cancer Institute, and the University of Oxford.

Essentially Research Kit provides researchers with a platform that they can use to build a data collection app and tap into Apple’s 700 million customer base. The API provides developers with a wealth of data points that they can then utilize to collect data in support of the study being conducted. Apple users will retain complete control over what data is shared, and what data will be kept private. Researchers can tap into the accelerometer, microphone, gyroscope and GPS sensors in the iPhone in order to collect a plethora of data. Five health systems have now developed apps in support of ongoing research efforts using the Research Kit framework and many more are sure to follow.

In retrospect, this seems a no-brainer. Apple’s apps “already help millions of customers track and improve their health,” said Jeff Williams, Apple’s senior vice president of operations, in a statement.

“With hundreds of millions of iPhones in use around the world, we saw an opportunity for Apple to have an even greater impact by empowering people to participate in and contribute to medical research.”

Jeff Williams SVP Operations Apple

2020

CASE STUDY: MEDIDATA AND GSK

Many mobile health innovation projects are already underway, however, Medidata, a provider of cloud-based solutions for clinical research in life sciences, recently announced the completion of a method development project conducted in partnership with GlaxoSmithKline plc (GSK) to evaluate the impact of unifying mHealth devices with cloud-based technologies in a clinical trial setting. The joint initiative assessed the capabilities of mHealth tools and evaluated how they could be used to enable a new model for clinical trial conduct that aligns site and patient needs with faster study execution and reduced costs.

Medidata and GSK provided program participants with two wearable devices – Vital Connect’s HealthPatch® MD and ActiGraph’s wGT3X-BT Monitor – which continuously measured vital signs, electrocardiogram (ECG) data and activity levels. Participants used Medidata Patient Cloud®, a mobile app for patient-reported outcomes offered as part of Medidata’s industry-leading technology platform. The participants carried smartphones that captured data from the mHealth devices, pulled this data into the Medidata Clinical Cloud® and then mapped it to the clinical record. Participants continued with their usual daily routine and only checked in with the performance lab at the project’s beginning and end.

“The effort indicated that mobile devices can support the long-term goal of lessening the burden on patients participating in studies by streamlining routine procedures, eliminating unnecessary ones and reducing visits to clinical trial sites,” said a statement from Medidata.

“We gathered data on an unprecedented scale—collecting more than 18 million data points on activity and vital signs per participant per day. This is an extraordinary level of in-life, real-time patient instrumentation for clinical trials, which will create new disciplines and new opportunities for life science companies,” said Glen de Vries, Medidata’s president.

Another project has seen Medidata strike a deal with Garmin to offer its clients the use of vívofit activity trackers in clinical trials. The choice of vívofit gives an indication of the characteristics clinical trial sponsors may prioritize as wearables start to take off in research.

This particular fitness wearable device has a remarkable one-year battery life and water resistance –features that mean a participant can wear it 24/7 for the duration of most studies. >




The Clinical Trials Transformation Initiative (CTTI) is the public-private partnership working to identify and promote practices with the aim of improving the quality and efficiency of clinical trials.

The CTTI states that currently available remote technologies, including, for example, mobile health delivery systems, telemedicine, and remote sensor devices, may increase the efficiency of clinical trials. The Initiative has now established a working group to look at “Using Mobile Technologies and Other Off-Site Methodologies to Facilitate Clinical Trials”.

They say that an increase in the use of mobile/remote technologies in clinical trials, could potentially lead to expanded improved patient experience, continuous high quality data acquisition, reduced costs, increased efficiency, and fewer losses to follow up.

“Mobile technologies hold the prospect of reducing or eliminating visits of trial participants to study sites and may result in more efficient and reliable data collection. The program aims to determine how mobile technologies can be used to improve clinical trials in areas of remote monitoring/engagement and new novel data collections methods to enhance knowledge of disease trajectory and treatment efficacy”

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Clinical trial sponsors have struggled for years with trial participants forgetting to complete patient-reported outcome (PRO) forms until the day of their site visit. This latest collaboration could fulfill the dream of continuous data collection is unappetizing for sponsors. The device tracks distance walked, steps taken, hours slept and calories burnt, is controlled by one button and shows fitness data on an LCD screen. In Medidata trials, all the data will be uploaded to its cloud-storage system, on which data crunchers can integrate the wearables’ feed with traditional sources of clinical research information.

Regulation is another issue of contention, but providers of mHealth solutions have been working closely with the FDA etc in order to ensure that data is FDA compatible.

The Agency recently issued guidance to provide clarity and predictability for manufacturers of mobile medical apps, and said “the Agency will continue to evaluate the potential impact these technologies might have on improving health care, reducing potential medical mistakes, and protecting patients.”




Along with understanding key unmet needs from the patient perspective, and integrating their voice into the development of new drugs, there is a need for pharma to work closer with regulatory agencies. “We’re all engaging with FDA and EMA,” says Marc M. Boutin, Executive Vice President and Chief Operating Officer, National Health Council. “It’s hard for FDA to be integrated into these efforts but they’re extremely interested in this – there is a great deal of work going on there in how they can facilitate patient engagement within companies.”

Patient groups are driving regulatory decision-making and science in directions that are more patient-focused,” says Tom Sellers, Senior Director, Patient Advocacy and Corporate Philanthropy, Takeda Oncology. “For example, we’re doing a patient preference study in multiple myeloma and have used our multiple myeloma ambassadors to focus group and develop it, and we are using the International Myeloma Foundation to field the survey,” he goes on. “This means we are leveraging the voice of the patient and when the survey is complete it will

reflect a range of views from patients, KOLs from academia and our company. That will be a much more powerful and robust result when you go to the FDA or a payer than a simple survey would be.”

The Holy Grail for pharma is having patients involved early on to help accelerate the regulatory process. “Such regulatory requirements will dictate the extent of patient centricity in a study,” comments Javier Zambrano, Director, Medical US Avonex/Plegridy, Biogen Idec.

Regulators must do more to involve patients, demands patient leader Jack Whelan. “Until educated, engaged patients are compensated for their time and effort participating as a thoughtful information resource, developers will continue to struggle to find reliable patient voices,” he says. “This is a regulatory issue. Except for their personal experiences as a patient, most patients are no more credible than ‘the man in the street’ until they become seriously involved in the management of their particular disease and engaged in the subject of drug development.”

The FDA and patient centricity:What are regulators doing?

CASE STUDY: MEDIDATA AND GSK continued…

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Efforts to more effectively incorporate the patients perspectives throughout the drug development pathway are growing, and the regulators are not only aware of this, but have made active progress in formalising this new approach to patient participation in clinical trials. The US FDA has made significant moves to give patients a more active role in medical product development and regulation, with the FDA Safety and Innovation Act enshrining this commitment to provide patients with an active role in the drug development process into legislation.

The FDA’s five-year project Patient Focused Drug Development (PFDD) was launched in 2012 and reflects a larger movement to ensure that patients’ perspectives are meaningfully integrated into the drug development process, as well as regulatory decision-making. According to the Administration, the patient perspective will provide “context in which regulatory decision-making is made, specifically the analysis of the severity of the condition treatment and the current state of the treatment armamentarium for a given disease”.

“We want to learn about the clinical context of each disease from the patients’ point of view and experiences,” said Theresa Mullin, Ph.D., director of the Office of Strategic Programs in the FDA’s Center for Drug Evaluation and Research (CDER).

The Administration worked to identify some 200 patient representatives based on their experience, FDA training, and clearance on conflicts of interest. By the end of 2017, 20 public meetings will have taken place, each targeting a specific disease, where patients are asked to assess their available treatment options and the therapeutic benefits that matter most to them.

Richard Klein, head of FDA’s patient liaison program in the Office of Health and Constituent Affairs, said at a recent conference on PFDD that qualified patient representatives not only have experience with a disease or condition, but are active in patient advocacy organizations, knowledgeable about treatment options, and able to grasp basic scientific principles.

These patient representatives are now engaging in consultations with FDA review divisions and in additional meetings with sponsors.

Over time, this increased attention to patient perspectives will “change the way clinical trials are designed and carried out,” Klein has observed. He has also said that patient input at pre-IND meetings can help design informed consent to encourage enrollment. He added, however, that the trickiest issue for including patients in sponsor meetings is screening for conflicts of interest.

Public participation has been strong, and the resulting reports are helpful in developing disease-specific guidance and new outcomes measurement tools. Patient groups have been enthusiastic and pro-active, and are now organizing additional external meetings to continue their discussions.

“We are gratified by the enthusiastic response within the patient community to PFDD, and we look forward to continued success with these meetings and the long-term benefit they can offer for drug development in important therapeutic areas,” Mullin has said.

She added that the “Voice of the Patient” reports published after each meeting “serve an important function in communicating to both the FDA review staff and the regulated industry what improvements patients would most like to see in their daily lives”. The FDA hopes that these reports will strengthen the structured framework for benefit-risk assessment in the new drug process required by FDASIA.

The FDA’s PFDD initiative has also inspired many companies within the pharmaceutical industry to re-think their original approach to patient engagement activities.

The FDA and patient centricity: What are regulators doing?

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The FDA and patient centricity: What are regulators doing?

“In the past, the industry’s approach to patient engagement was primarily anecdotal and ad hoc, with a project here and there,” said David Verbraska, VP, worldwide public affairs and policy at Pfizer, agreed. “By being patient-centric and adding transparency and interaction all along the R&D and market life cycle, patients help us achieve the best public health outcomes and avoid the worst-case scenario,” he said – this worst case scenario being a drug receiving approval from the FDA that does not in fact meet patients’ needs.

Mullin recently proposed important next steps as patient-centered drug development continues to grow and become embedded in clinical trial protocol. She said the goal should be to 1) advance the science of patient input and 2) provide FDA guidance to patient advocates and drug developers.

Mullin has also commented that companies “could play an important role in collaborating with patient groups and researchers in follow-up work to develop clinical outcome assessment tools or patient-reported outcome measures for clinical trials that will better capture the patients’ perspectives.”

Paul Kluetz, Acting Deputy Office Director of the FDA Office of Hematology and Oncology Products, has previously clarified that the Agency’s Patient-Reported Outcome (PRO) guidance outlined in 2009 was very necessary, as many innovators had been trying to develop instruments in the absence of FDA recommendations of a systematic approach.

As the FDA pursues an approach that is more flexible and conducive to innovation, it is important that the Agency continue to make progress to provide timely and robust feedback to those seeking to develop and use clinical outcome assessments, and continue to consider ways to improve communication to stakeholders of complex regulatory decisions.

In line with the FDA’s patient-centered activities, the regulators are now reaching out to the public to ask what more they can do to improve their efforts. Last year the FDA released a new Federal Register posting indicating that it will establish a federal docket to allow members of the public – and in particular patients and patient groups – to weigh in on “FDA activities performed under the FDASIA Patient Participation in Medical Product Discussions”.

The intent is to gather input from stakeholders on “strategies to obtain the views of patients during the medical product development process and ways to consider patients’ perspectives during regulatory discussions”, according to the FDA. It is also seeking feedback from patients about sponsor meetings.

The FDA has said that the hope is that the long-term impact of the PFDD program will be a “better, more informed understanding of how the entire drug development community might find ways to develop new treatments for diseases”.

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Expectations and outlook

Looking ahead at what can be done, Joel Beetsch, Vice President of Patient Advocacy at Celgene thinks the industry should focus on three key priorities for the Patient-Centered Clinical Trial:

• Starting with patient-friendly and patient-focused endpoints.

• Further identification of patient-reported outcomes and quality-of-life metrics.

• Major emphasis on data sharing throughout the overall trial process.

He explains that the last point “can shorten the process – and saves money – and helps us avoid having to collect unnecessary data from patients.” Beetch points to the PhRMA and EFPIA principles on sharing data around clinical trials which were instituted on January 1, 2014, and another data sharing project, the Project Data Sphere initiative. “It enables us to share, integrate, and analyze our collective historical cancer research data in a single location, so researchers can share the control arm of Phase III clinical trials,” he explains.

Electronic health records have the potential to be a tremendous tool in bringing the right trial to the right patient, suggests Jennifer Byrne, PMG’s Chief Executive Officer. “Patients can be significantly empowered in decision-making regarding their health by having more information as to what clinical trials might be available to them as a care option for their condition or disease,” she says. “In addition, wearable devices will provide real-time surveillance to health care providers and stand to further promote patient safety, compliance, and data integrity.”

The migration to a personal health record will certainly lead to more engaged patients and thus more engaged trial participants, thinks David Vulcano, AVP & Responsible Executive for Clinical Research, Hospital Corporation of America. “Integrating electronic health records with other healthcare information systems can be used to facilitate communication and build relationships with patients,” agrees Greg Koski of ACRES.

The development and implementation of standards and APIs to enable wide-scale integration of information platforms, especially with regard to drug safety, clinical trial and health information will empower patients and improve the clinical trials process, he continues. Koski cites the example of a project on which ACRES is collaborating with the Swiss Institute of Technology that enables patients to

‘deposit’ their electronic health records into a secure repository and retain control over who has access to them and how they will be used. While the future is notoriously hard to predict, one thing is certain: patients’ health information is personal and private, which means patients will increasingly control access.

“Our customer is the patient. If you’re serving the patient, the business will succeed.”

Tom Sellers Senior Director, Patient Advocacy and Corporate Philanthropy, Takeda Oncology

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Conclusion

As the roadmap in this paper exemplifies, patient centricity is here to stay. Pharma now needs to translate the ideas into actions, elevating it from the buzzword bubble to working organizational reality. It is fair to say that the impact of existing patient engagement activities is rarely being measured by the industry and more metrics are required to reinforce the case for doing so. We need a master framework.

Internally, patient centricity must be deeply engrained in a company’s values and performance management systems. Pharma can innovate and readjust organizational structures and drive cross-functional partnerships to win over patients, contain budgets, and manage studies more effectively. However, there is resistance to change legacy systems and a degree of fear about engaging with the patient (for reasons including compliance and lack of control over outcomes).

“You have to start in multiple places and bring teams together”, explains Roslyn F. Schneider of Pfizer. “For example, later in development, market research, patient adherence and customer engagement related to many of our already-marketed products. Many people in teams earlier in development may not have been exposed to this thinking and approach.”

There is more work to be done throughout the industry but a few companies have already shown that change can be achieved and, through their examples, it is possible to begin plotting a roadmap for the future. As with anything, change requires the commitment of leadership, after which the rest often follows. eyeforpharma’s most recent industry survey shows that senior management and board level buy-in is vital for companies which are serious about furthering patient-centred drug development (n=165). In pharma companies where no one spearheads patient centricity, only 21% of respondents consider it a top priority. Similarly, where it isn’t considered a top priority, only one in five respondents recognize senior leadership efforts. But where corporate management spearheads patient centricity, 76% confirm that is has been the top priority for their organization in 2015.

How can they start the process? “Transparency and education are the critical first steps to empowering patients, and new technologies that help the research community more readily share information and engage with patients

and the public may prove to be of great value,” says Zach Hallinan, Director of Patient Communication and Engagement Programs at CISCRP. “However, our focus should rarely be on the technology itself. Most important is creating opportunities for patients and research professionals to interact and learn from one another in meaningful ways, and the most innovative approaches will be those that put human connections first.”

If companies are wondering internally what they can “get out” of patient centricity, they are surely thinking about it in the wrong way.

“That’s what distinguishes a patient-centric company from a traditional one,” suggests Tom Sellers, Senior Director, Patient Advocacy and Corporate Philanthropy at Takeda Oncology. “A patient-centric company is not starting with that question per se. If you’re truly putting patients first then you don’t have to convince the company that there’s a financial benefit. In most other businesses, if you’re satisfying the customers’ needs then you’re going to do well. Our customer is the patient. And if you’re serving the patient then the business will succeed.”

38%of clinical trials professionals are planning to leverage e-clinical technologies and mHealth applications in the near future

57%of respondents think that

Adaptive Trial Design will have a huge impact on reducing

clinical trial costs

WHAT THE FUTURE HOLDS:

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Documents

PCDD – A Roadmap