In 2010, a little-known research institute, the Patient Centered Outcomes Research Institute (PCORI), began funding hundreds of clinical studies with the aim of increasing the value of medical innovation. These studies included patients and family members in every step of the research process. This approach, called patient-centered outcomes research, has become a novel tool for conducting health care investigations; but, it raises ethical issues, which have largely been pushed to the background.
Anyone working in medical research over the past 10 years can testify that engaging patients and incorporating their perspectives has become popular across the medical research industry. Patient-centered care is mentioned more than 40 times in the Affordable Care Act, which served to establish PCORI, the pioneer and leading source of funding for this type of research.
In traditional clinical research, investigators conceive of and implement research, while those who volunteer to be "subjects" have little or no say in the process. In patient-centered outcomes research, patients are active participants throughout the entire life cycle of research projects, from coming up with ideas for research, to designing and overseeing studies and disseminating the results. This approach has since been echoed in initiatives by the FDA, the Institute of Medicine, and the 21st Century Cures Act to give patients a voice in the design and conduct of clinical trials.
As researchers, we were drawn to the challenge of finding answers to the many ethical questions that arise when patients take active roles in medical research—when they step beyond the role of “subject” to work alongside researchers, acting as co-investigators, recruiters, or advisors.
This new level of patient involvement can create massive complications for the oversight bodies (HRPPs, IRBs, etc.) charged with overseeing research. And, because having patients in non-traditional roles is still new, IRBs have not yet fostered a framework to deal with the accompanying challenges.
We wanted to find out: What is the appropriate level of ethical and scientific training for patients in these non-traditional roles? Should it be the same as for researchers? How should IRBs provide effective oversight of these patients without imposing unnecessary protections that could stifle patient engagement? How can patients be involved when they are being paid by pharmaceutical companies with a stake in the research and there are conflicts of interest?
Surveying the Field
To do this, we conducted a multi-year research project funded by PCORI that brought together social scientists and experts in human subjects protections and oversight to explore the ethical issues raised by patient-centered outcomes research. We hoped that the results would help IRBs, the bodies responsible for overseeing clinical research, navigate the complex ethical issues that patient involvement in research can raise.
We conducted a series of interviews and focus groups with more than 100 researchers, patients, patient advocates, and IRB members, and also completed the first-ever national survey of IRB chairs.
One-quarter of survey respondents said that their IRBs view patients in non-traditional roles as research subjects, even if they are not formally enrolled as subjects in the study; 37 percent said that their IRB requires informed consent from patients in non-traditional roles , meaning they must acknowledge that they understand they may be at risk from an unproven therapy or treatment—just as they would a regular, traditional research subject. But requiring this of patients in research roles, when other researchers on the team are not required to give informed consent, could be seen as overbearing, paternalistic, and a threat to patient engagement.
Our work also suggested uncertainty about how IRBs and research teams should handle research in which patients want to simultaneously occupy multiple roles in the same study, such as team member and subject, or switch between roles—a situation not uncommon in patient-centered outcomes research.
Survey respondents expressed concerns over emerging evidence of widespread industry funding of patient advocacy groups, and we investigated whether specific rules and regulations are necessary to mitigate potential conflicts of interest in situations where a patient is funded by a corporation.
To address the many ethical issues that survey respondents pinpointed, we then held multiple rounds of discussions with a 17-member panel that included patients and patient advocates, principal investigators of patient-centered outcomes research, IRB chairs, experts in bioethics and law, and policymakers.
The panel ultimately reached consensus on 21 recommendations for addressing challenges for the oversight of patient-centered outcomes research, which were published October 16, 2018 in Annals of Internal Medicine.
There was strong agreement that IRBs and other oversight organizations should resist the tendency to hold patients to a higher standard than others involved in research just because they are patients, such as the need to give informed consent.
The panel endorsed formally classifying three distinct roles that patients might occupy in patient-centered outcomes research—study personnel, advisor, and research subject—and laid out criteria for determining each of these roles.
The panel also called for patients in non-traditional roles to receive standard ethics training (such as the Collaborative Institutional Training Initiative program) at a minimum, and suggested that PCORI consider developing modules to provide further ethics training tailored for patients and the challenges they may encounter.
The panel also called for more guidance from PCORI, or another high-level policy body, on how IRB’s might identify potential patients to get involved in research in non-traditional roles, including the importance of achieving a diverse mix of patient partners.
For patient-centered research to flourish, IRBs and other oversight bodies must be confident reviewing it and analyzing the ethical challenges it raises.
As medical research continues to evolve in innovative ways, now is the time to lay some ground rules about including non-traditional staff on research teams, and how a variety of backgrounds and situations can compound IRBs’ responsibility to oversee ethical research across the country.
Without an actionable framework for how IRBs can incorporate non-traditional teams into the research process, patients will undoubtedly face ethically dubious situations, corporations could elbow their way deeper into the research space, and the regulations that guide IRBs now will be further out of date than they are now.
Luke Gelinas, PhD, chairs the Advarra institutional review board and was a senior researcher on the Patient-Centered Outcomes Research Oversight Study at the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.
Joel S. Weissman, PhD, is deputy director and chief scientific officer of the Center for Surgery and Public Health at Brigham and Women's Hospital in Boston, and professor of surgery in Health Policy at Harvard Medical School. He conducts health services research in the areas of surgery, advance care planning, patient engagement in care and research, payment reform, and disparities/vulnerable populations.
I. Glenn Cohen, PhD, is the professor of law and faculty director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics, Harvard Law School, Boston. His research is focused on big data, health information technologies, mobile health, reproduction/reproductive technology, research ethics, rationing in law and medicine, health policy, FDA law, and translational medicine, among other areas.
The Center for Surgery and Public Health (CSPH) at Brigham and Women’s Hospital was established in 2005 as a joint program of Harvard Medical School and the Harvard T. H. Chan School of Public Health. Its mission is to advance the science of surgical care delivery by studying effectiveness, quality, equity, and value at the population level, and developing surgeon-scientists committed to excellence in these areas. CSPH works with a diverse set of collaborators, including academic institutions, non-profit and for-profit organizations nationally and internationally, in order to eliminate disparities and foster patient-centered care through policy and practice.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. The Brigham’s medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH’s online newsroom.
The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School was founded in 2005 through a generous gift from Joseph H. Flom and the Carroll and Milton Petrie Foundation. The Center’s founding mission was to promote interdisciplinary analysis and legal scholarship in these fields. Today, the Center has grown into a leading research program dedicated to the unbiased legal and ethical analysis of pressing questions facing health policymakers, medical professionals, patients, families, and others who influence and are influenced by health care and the health care system. To achieve this goal, the Center fosters a community of leading intellectuals, practitioners, and policymakers from a variety of backgrounds at all stages in their careers, across Harvard University and across the world.
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