In a recent PCT Grand Rounds, Drs. Naggie, Hernandez, and Perakslis of Duke University discussed the impacts of the COVID-19 outbreak on the conduct of clinical trials. The panel described the status of COVID-19, its impact on trials currently begin conducted, some key questions to consider, and potential solutions and approaches. A brief Q&A followed the presentation.
View the video and download the slides from the webinar.
Another research model is to implement direct-to-participant trials that are streamlined, personalized, and potentially safer.
Discussion Themes
Do you anticipate that statisticians will need to account for period effect in later analysis of data (pre/post COVID-19)?
Are there lessons learned from the last epidemics, for example H1N1 or Ebola? How can we deal with global pandemics in the future?
What about clinical trials in the elderly population, given that they are the most vulnerable to the coronavirus and may not be as good with technology as younger participants?
Would it be possible to set up a multisite telehealth-based outbreak learning health unit?
Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the UG3 PRISM NIH Collaboratory Trials. These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.
Six NIH Collaboratory Trials—ACP PEACE, EMBED, GGC4H, HiLo, Nudge, and PRIM-ER—have recently transitioned from the planning to implementation phase of their embedded pragmatic clinical trial (ePCT). During the transition, study teams reviewed and updated their ethics and regulatory meeting minutes from discussions with the Ethics and Regulatory Core. The minutes describe ethics and regulatory issues the trials have encountered, along with approaches the trials are using for informed consent, HIPAA, and monitoring and oversight:
Ethics and regulatory issues can pose challenges to embedded pragmatic trials because of the unique nature of clinical research conducted in the setting of routine clinical care. The Ethics and Regulatory Core provides assistance to study teams as they navigate the ethics and regulatory landscape of ePCTs.
Findings from a new article suggest that the majority of patients do not feel a personal responsibility to participate in clinical research. In the article, Kevin Weinfurt, Li Lin, and Jeremy Sugarman report the results of a national survey of nearly 3000 people regarding their attitudes towards research responsibilities as well as their trust in doctors, healthcare systems, and medical research. Ethical frameworks for learning health systems have suggested that patients have a responsibility to contribute to learning activities, including research. The findings from this survey suggest that most patients in the U.S. do not currently endorse such a responsibility.
“These data provide a useful snapshot of the public’s views toward the obligation to participate in research. It is unclear how, if at all, these views will shift with increased efforts to create mature learning health systems. And if such views do not shift, it is uncertain what that would mean for the success of learning health systems.” —Kevin Weinfurt, PhD
Read the full article: Public Views Regarding the Responsibility of Patients, Clinicians, and Institutions to Participate in Research in the U.S.
Robert J. Mentz, MD, FACC, FAHA, FHFSA
Associate Professor
Director, Duke Cooperative Cardiovascular Society
Associate Program Director, Duke Cardiovascular Disease Fellowship
Duke University Medical Center and Duke Clinical Research Institute
Topic
Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System
Keywords
International Council for Harmonization (ICH); Good clinical practice (GCP); Learning health system; Pragmatic clinical trials; Institutional review board (IRB); Research oversight; Regulatory issues; Quality by design (QbD)
Key Points
Good clinical practice (GCP) guidance details the responsibilities, procedures, and recording that are necessary for appropriate trial conduct; for example, conducting the trial in accordance with an IRB-approved protocol with appropriate adverse event monitoring and reporting.
There is an urgent need to streamline randomized trials. Key obstacles are lack of transparency, lack of representativeness, and lack of evidence of competence.
In the United States, clinical investigators must abide by guidance from FDA, HHS, and ICH-GCP. Yet it is hard for investigators to keep track and to know how GCP applies to their study.
GCP as an overall construct is useful, but it does not deal well with issues particular to pragmatic trials or trials outside the FDA-regulated world.
Discussion Themes
With embedded pragmatic trials, informed consent is more nuanced. New considerations and approaches for consent have arisen since ICH GCP first came into effect.
Establishing quality by design will take time, effort, and educating IRBs to understand how QbD can be used to avoid errors in a trial and collect data that is fit-for-purpose.
It’s crucial that trials address an important question, answer that question reliably, and keep participants safe.
A panel funded by the Patient-Centered Outcomes Research Institute (PCORI) recently published recommendations for the oversight of patients who participate in research roles other than as “research subject.” Patients and caregivers participate in many roles, such as co-investigators, study personnel, and advisors in research studies, and this creates novel ethical and regulatory challenges. The panel provides a taxonomy for these roles and recommendations for appropriate oversight. The group also provides recommendations about identifying and engaging a diverse mix of patients and developing mechanisms to protect against possible conflicts of interest. Finally, given the ubiquity of mobile health and other emerging technologies for use by patients, the recommendations provide guidance about the inclusion of these technologies in patient-centered outcomes research, with specific attention to education, best practices, and appropriate privacy protections.
In an accompanying editorial, Dr. Robert Califf expressed his support for the panel’s efforts and their taxonomy for patients in patient-centered outcomes research:
“Given the persistent gap between the slow pace of research and the pressing need for high-quality evidence to guide practice in areas of clinical uncertainty on one hand, and the potential offered by more pragmatic, people-centered research methods on the other, we need positive approaches for making learning through research a routine part of clinical care rather than an exceptional event.”
Khaled El Emam, PhD
Department of Pediatrics, University of Ottawa
Children’s Hospital of Eastern Ontario Research Institute
Topic
Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets
Keywords
Clinical trials; Research ethics; Data security; Data sharing; Sensitive research data; De-identified data
Key Points
The cycle of risk de-identification involves setting a risk threshold, measuring the risk, evaluating the risk, and applying transformations to reduce the risk.
The Safe Harbor method of de-identification (removal of 18 categories of data) is a legal minimum standard that does not take context into account, and may not be sufficient when sharing sensitive data publicly.
A higher standard for de-identification is the “Expert Determination” method, whereby an expert with contextual knowledge of the broader data ecosystem can determine whether the risk is “not greater than very small.”
With increasing concern about the risks of sensitive data sharing, it is important to be transparent with data participants and continue to build trust for data uses.
Discussion Themes
When is a dataset safe for sharing? What is the risk of re-identification, and how can we reduce the risk? Consider who you are releasing the data to and what other kinds of data might they have access to that could potentially lead to re-identification.
For more information on the de-identification of protected health information, visit the U.S. Department of Health and Human Services’s Guidance Regarding Methods for De-identification of Protected Health Information in Accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.
The Health Information Trust Alliance de-identification framework identifies 12 criteria for a successful de-identification program and methodology.
On January 17, 2018, the Department of Health and Human Services and 15 other federal departments and agencies announced a delay to both the effective and compliance dates for the revisions to the “Federal Policy for the Protection of Human Subjects” (also known as the Common Rule). Most provisions in the revised Common Rule were scheduled to go into effect on January 19, 2018. The Interim Final Rule announced a delay until July 19, 2018, with the option for further delay, to give institutions additional time to prepare to implement the revisions. Before July 19, 2018, institutions may only begin implementing provisions of the revised Common Rule that do not conflict with the pre-2018 Common Rule.
A notice of proposed rulemaking (NPRM) is also in development to seek public comment on a proposal for further delay in the required implementation of the revised Common Rule (for example, until January 21, 2019). A decision will be made after considering public comments.
We recently asked Drs. Jeremy Sugarman and Kevin Weinfurt, Co-chairs of the Ethics and Regulatory Core, to reflect on the first 5 years of the Core as well as on the challenges ahead. The regulatory and ethical landscape for pragmatic clinical trials was not well defined when the Core began 5 years ago, and the Core helped to map and navigate the emerging landscape to enable the implementation of NIH Collaboratory Trials in ways that satisfied ethical and regulatory criteria.
“The Core’s work has led to the creation of a substantial body of scholarship contributing to the ongoing policy and ethics debates about pragmatic clinical trials.” – Drs. Sugarman and Weinfurt
In a recent PCT Grand Rounds, Drs. Naggie, Hernandez, and Perakslis of Duke University discussed the impacts of the COVID-19 outbreak on the conduct of clinical trials. The panel described the status of COVID-19, its impact on trials currently begin conducted, some key questions to consider, and potential solutions and approaches. A brief Q&A followed the presentation.