data & technology

PRT ARTICLE

50 THE PHARMA REVIEW ■ NOVEMBER - DECEMBER 2015

Data & Technology in Clinical Trials 2015An Industry View Point: The Future of Leveraging Data and Technology in Clinical Trials.

eyeforpharma’s State of the Industry Survey investigated how the pharmaceutical industry are leveraging, or plan to leverage, data and technology in European clinical trials."An Industry View Point: The Future of Leveraging Data & Technology in Clinical Trials" looks at the Survey findings in detail, with commentary from industry experts Joseph Kim (Eli Lilly) and Jeffrey Kasher (DrugDev) on how best to leverage the latest technologies and data innovations and prioritize patient need.

The SurveyThe survey comprised eight questions covering methods currently employed in clinical trials, methods to be implemented, the impact of data collection and analysis methods, current challenges, and patient-centricity.Respondents were industry professionals from the areas of research (22.47%), general management (21.35%), operations (20.22%), development (17.98%), data (10.11%), design (5.62%), and outsourcing (2.25%).

Clinical Trial Methods – Risk-Based Strategies Growing In PopularityCurrently, small patient studies are being deployed or piloted by 65.17% of respondents, while risk-based strategies (49.44%)

Figure 1: Clinical function of respondents

and adaptive trials (48.31%) aren’t far behind. Dropping down the scale in popularity are applied real-world data in trial design (33.71%) and data modeling and simulation (28.09%).Of the clinical trial methods planned for deployment by companies within the next two years, risk-based strategies moved up to first place (58.43%), closely followed by adaptive trials (52.81%). Small patient studies dropped from first to third place at 43.82%.The picture changed when respondents were asked which methods would have the most impact in five years’ time. Remaining at the top of the list of priorities were adaptive trials and risk-based strategies. However, small patient studies moved to the bottom of the list, even below applied real-world data and data modelling and simulation. In other words, the most frequently deployed methodology currently – small patient studies - is believed to offer the least effectiveness in the next 5 years. Still, pharma are set to address this by focusing on riskbased and adaptive strategies over the next 2 years, with one respondent, noting, “The biggest area of investment would be to fully implement risk-based monitoring principles and remote monitoring.”This move towards risk-based monitoring (RBM) is supported by other research within the field1:

Joseph Kim, Jeffrey Kasher & Nassim Azzi*

*Global Project Director, eyeforpharma, Email: [email protected] (Author for Correspondence)

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51THE PHARMA REVIEW ■ NOVEMBER - DECEMBER 2015

Figure 2: Trial methods planned within the next 2 years

Figure 3: RBM utilization, MCC survey 2013

Figure 4: Key reasons for adopting RBM, MCC survey 2013

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The necessity to move towards RBM is also supported by Joseph Kim, Senior Advisor in Clinical Innovation, Eli Lilly: “Currently, we typically send a human being out to a site and they look at the data, compare it the source and try to find errors and omissions in data. But it’s expensive to clean data in this way. Not to mention, even the smartest human isn’t going to be able to catch patient or sitewide trends that could pop up. With central monitoring and more powerful statistical models and algorithms - not to analyze the data but to analyze the data quality – you can start to ascertain with greater certainty that: a) there's no foul play; b) people are well trained and the data is coming in as it should; and, c) patients are also doing things correctly.” These key reasons for adopting RBM are supported by other research within the field (Figure 4).By using RBM, you can identify the necessary data to answer the specific questions in your trials, while bypassing unnecessary data. Jeffrey Kasher, Chairman of the DrugDev Advisory Board, says, "I was fortunate to be sponsor of the TransCelerate working team that developed and published the RBM guidance. I believe implementation is going well, especially when you consider how large of a change it represents.”He adds, “Initially, there was confusion between sponsors/CROs and sites as to exactly what RBM was and was not. There has been a lot of dialogue which has brought people to a common understanding. The large remaining opportunity is for sponsors to identify and address risk factors in protocols while in the stage of protocol design. Modifying trial design or ensuring safeguards are put in place for the highest risk data elements will yield better, higher quality, trials."

Future Investments – Data Leads The WayFindings from the survey indicate that future investments in the next 2 years will be largely directed towards data, with order of potential investment then being: research, development, operations, design, and general management. A total of 85.39% of respondents agreed that improving the collection, analysis and management of data would have the biggest impact on how future clinical trials will be conducted.

Qualitative responses demonstrated some clear strategies for how pharma could better invest in data in the future, including utilizing real-world and big data, as well as remaining focused on patient-centricity.

Real-World DataSurvey respondents felt that, “Data needs to be as close to real-world as possible,” and that the collection of real-time data is one of the biggest opportunities for better use of clinical data in the near future. Real-world data provides faster data generation, demonstrates value to patients quickly, and increases patient recruitment. It was noted that, “Collecting real-time data relevant to people has to be an improvement on scales based on population norms.” Indeed, it was expressed that communication in real-time could facilitate finding urgent answers to unmet needs.

Big DataA significant number of respondents believed that big data is where the opportunities are for future clinical trials. Big data facilitates the challenge of finding innovative therapies, by identifying sub-groups of patients to target the right therapy to the right patient. It also allows for the integration of patients and patient associations into clinical research to help define the right biomarkers. “As R&D becomes more expensive and there are less new innovative molecules in development, the new way to do R&D will be looking into big data and getting the most out of it to develop new drugs and/or target specific needs and populations,” offered one respondent.It appears from responses that one way of achieving better utilization of big data is through “data mining and meta-analyses” and “data sharing between companies for the common good.” It was pointed out that, “Everyone has these information-rich datasets that could be used for other trials.” Data sharing isn’t just about sharing positive results, however, the need to include failed studies within any data sharing initiatives was emphasized.

Patient-CentricityRunning more patient-focused trials was currently the biggest focus for 66.29% of respondents. Patient-centricity was referred

Figure 5: Consensus that the collection, analysis and management of data will have the biggest impact on how future trials are conducted

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to in a variety of ways, including the need for “personalized data,” “specialized medicine,” and the recommendation to “use data from reimbursement and individualized treatment.” The need to embrace patient reported outcome measures PROMs was also highlighted in efforts to achieve “data collection directly from the patient” and “improve patient-reported outcome quality and collection.” It was believed that one way forward was the “integration of PROMs data into clinical trials.”"Participants aren’t an amalgamation of what you read in scientific papers. They aren’t a faceless person. They are your wife or brother. If your loved ones are about to enroll in a clinical trial, what would you want for them to make it patient-friendly?"Joseph Kim, Senior Advisor in Clinical Innovation, Eli LillyIt was highlighted within the survey that, “The priority is patient-centric trials,” and that, “Evidence collected in clinical trials has to go down to the individual patient. Personalized medicine may further evolve as evidence/data grows. This may mean better efficiency in treatments, cost-effectiveness, and possibly a reduction in adverse events.”Patient-centricity remains somewhat of a buzzword, so how can pharma move it from being a buzzword to an actual way of working? According to Kim, it isn’t brain science – “Put yourself in the role of the patient. What would you want as a patient?” He adds, “Participants aren’t an amalgamation of what you read in scientific papers. They aren’t a faceless person. They are your wife or brother. If your loved ones are about to enroll in a clinical trial, what would you want for them to make it patient-friendly?”Patient-centricity in trials holds many benefits, not least of which includes enhanced recruitment and retention. It can often unearth areas of unmet patient need. The National Cancer Research Institute Clinical Study Group has patient representatives to help inform discussions on trial design at their meetings. Another

example of the effectiveness of patient involvement discovering unmet needs was brought forth by Julie Flygare of Project Sleep. By getting together with other narcolepsy patients, a new symptom was identified as a new, potential clinical endpoint to pursue – ‘brain fog’ – which wasn’t on anyone’s radar. Flygare did this without a Pharma partnership, “But imagine the value of being able to purposely harness patients insights so they can help come up with the new endpoints and unmet needs,” says Kim.

Current Challenges – it’s not All About BudgetBudgetary pressures are by far the biggest challenge, according to survey findings, followed by identifying and maintaining patients, managing timelines, integrating new technologies into the trials process, finding and implementing new systems and software, developing trials that answer initial questions, reducing silos between different functions/departments, establishing and maintaining relationships with CROs, and CRO selection.Kasher observes, “The top 3 challenges in the survey build on and compound each other. Project teams are under pressure to get a new trial started (timeline), which results in limited time for real-world data feasibility analysis, patient input, and site input.” According to him, this means that trials get started and due to design flaws, it is hard to recruit and/or retain patients in the trial. This leads to additional sites being added and prolonged timelines. He advises,"Slow down prior to starting the trial; it will result in completion of the trial on time, on budget, and with quality."Jeffrey Kasher, Chairman of the DrugDev Advisory BoardKim also offers some advice: “Budgeting is a multi-variable discipline. Ultimately, the speed of clinical trials is the most important metric to improve. Patient enrollment is the leading cause of delays in drug development. People choose not to participate. They're not inspired to participate. The health care system isn’t incentivized to make that happen. So, if we can accelerate the call to action from patients that is probably the best way to reduce budgets and the costs of developing drugs.”We provide some strategies for overcoming the challenges of patient recruitment and retention, and managing timelines, all of which can have a direct impact on cost-effectiveness. At the core of these strategies is the leveraging of technology.Kim points to the Internet as one key way to enhance enrollment in clinical trials. However, he also cautions that the real question isn’t about how to leverage technology, but, “How do we leverage the Internet as it applies to the real brick and mortar world, so that more patients can actually participate? And what does that mean for study design?”

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Figure 6: Challenges to respondents’ current role, ranked according to biggest impact

Mobile TechnologyRespondents indicate that “mobile technology” might offer such convenience, as well as, “Integration of new technologies and implementing new systems to manage data.” Kim agrees that, “If we want to increase the ability of more patients to participate, we need to think about more creative ways to let them participate. Just like online banking has changed the way banking is, can we virtualize some part of the clinical trial or activate retail health care providers in conjunction with the investigator, so that patients can participate in a way that's really convenient for them?”Wearable technology is another way of enhancing data capture, data quality and facilitate data sharing to cut costs and drive efficiency. According to Kim, wearables promise the ability to provide better objective data than, for example, questionnaires. Giving an example of how depression is frequently measured via questionnaires and structured interviews, Kim asks, “Could an activity monitor be a better indicator of whether a patient’s depression is improving? One could argue yes, since wearables can measure real-world data such as physical activity, which might not just be a good indicator of improvement for depression, but for pain.” However, he does highlight that just assuming wearables are better than questionnaires isn’t enough. “You’ve still got to do the validation studies to prove it,” he says.

AppsAccording to Kim, Apple’s ResearchKit is a milestone in clinical research. He says, “One of the most valuable companies in the world has taken a first step in trying to create a platform where anybody with a smart phone can start to participate in research.

One of the first bright spots was the Stanford MyHeart health study, which enrolled 10,000 patients in one day. To do that in a day is unheard of.” He adds, “It’s only a matter of time before smart phones are the dominant channel to the Internet, which also means access to health information and participation in health care.” Kim and others believe this could be as soon as two to three years’ time.

Social MediaSocial media is another key player in leveraging technology to improve patient retention. Kim says, “Social media can be powerful in terms of accelerating health related information and empowering patients.” Despite this, the top companies on social media for 2014 don’t include any pharma companies. Exceptions to this are Novartis; they recently leveraged the power of Twitter (@NovartisCancrUS) to keep their 10,000+ followers engaged and motivated during cancer trials in the US. In this campaign, Tweets comprise promotions of cancer trials, with most tweets achieving engagement with patients, healthcare providers, or organizations. Appeals to retweet information on trials are also made, meaning that their reach is much wider than their followers alone. Also, hashtags are used to target tweets to certain cancer types (i.e. #breastcancer). Patient engagement is also enhanced by tweets about trials being linked to relevant information sources, where patients and professionals can investigate further and make informed decisions. One of the information sources some tweets link to is the Novartis Clinical Trials website, which offers more global support and helps visitors find clinical trials anywhere in the world.

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Case StudyCuring Through ConnectionAnother example of the power of social media is that of e-patient Dave de Bronkart, who was diagnosed with Stage IV, Grade 4 renal cell carcinoma in 2007. His median survival time at diagnosis was predicted to be 24 weeks, and his doctor prescribed him to visit an online social media forum to learn more about the disease from other patients. He discovered a therapy not widely used but that had good efficacy with some people. After removal of the tumor and a Biologic Therapy program, he was able to take part in a clinical trial for High Dosage Interleukin-2; he was cancer-free 6-months after diagnosis. “That only happened with social media,” says Kim. “Social media isn't the power of liking and sharing. The idea is that you're connecting information and aggregating it. We're all getting wiser due to this wisdom of crowds that can only be attained when you connect a bunch of people together in a fast and furious way.”

The State of The Industryeyeforpharma’s State of the Industry Survey, combined with case studies and expert insights from Kim and Kasher, highlight

About The AuthorsNassim Azzi is a Global Project Director at eyeforpharma and heads up the Clinical Trials Initiative USA. As a part of the initiative, he has been bringing together and working closely with clinical thought leaders and game changers from the Pharmaceutical Industry and other key stakeholders to help implement meaningful transformations to the clinical trial enterprise. He holds an MBA from the Johns Hopkins Carey Business School and has lived and worked on three continents and is fluent in three languages.Joseph Kim serves as a Senior Advisor in Clinical Development Innovation at Eli

Lilly, focusing on developing and implementing innovative patient engagement solutions. He has spent over 15 years in the pharmaceutical industry utilizing a unique approach that integrates his experiences working for sponsors such as Shire and Merck, CROs, and technology vendors. He has a robust combination of experience that includes early and late phase clinical research, and a well-known history of innovation in the clinical research industry, recognized as one of “Top 100 individuals on the 2015 MedicineMakers Power List, and “20 Innovators Changing the Face of the Clinical Trials Industry” by CenterWatch in 2013. Follow him on Twitter: @JoPeKim

Jeffrey Kasher, Ph.D., became Chairman of the DrugDev Advisory Board this year, joining a distinguished team of current and former clinical research executives from many of the leading pharmaceutical companies in the world. Dr. Kasher is passionate about improving outcomes, bringing patient and research sites into the development process, and dramatically decreasing the time to market for promising drug candidates. He is known as a pharmaceutical development change catalyst who brings to the role 28 years of leadership experience at Eli Lilly, where most recently he managed a portfolio of innovative clinical development approaches to achieve

50% cost and time reductions to be realized over a five-year period beginning in 2017. In addition to his role at DrugDev, Dr. Kasher is President of Patients Can’t Wait, was a founding member of the TransCelerate Biopharma Operations Committee and the Avoca Quality Consortium, sits on the DPharm Europe steering committee and faculty, and is a member of Linking Leaders. In 2013, CenterWatch named Dr. Kasher one of the “20 Innovators Changing the Face of the Clinical Trials Industry.” Follow DrugDev on Twitter: @DrugDev

the need for pharma to better leverage data and technology to improve the quality of clinical trials. This can be achieved through more careful consideration of trial design at the outset, more effective data collection methods during trials, and greater transparency with outcomes. One of the key ways to achieve this is by embedding patient centricity throughout all stages of the clinical trial process. As Kasher points out, “Patients are the ones who invest themselves in clinical trials (their bodies, their lives) and therefore they should have input into the design of the trial, receive support during the trial, and receive their results (written so they can be understood) upon completion of the trial.”The challenge, then, is how to enhance patient-centricity? The Internet, mobile technology, and social media may be the answer. Overall, pharma needs to harness the power of data, maximize technology, and design around the patient.

Sources:1. Taking the Risk: An Examination of Current Organizational Approaches

and e-Data Sources Driving Risk-Based Monitoring Programs. Risk Based Monitoring Full Report, 2014. Metrics Champion Consortium. 2014.

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