March 7, 2024: New Report Sets Out Posttrial Responsibilities in Pragmatic Clinical Trials

Headshot of Dr. Stepanie Morain
Dr. Stephanie Morain

In a new report from the NIH Pragmatic Trials Collaboratory, a team of bioethicists and implementation scientists argue for a “presumptive default” that the results of pragmatic clinical trials should be incorporated into healthcare delivery processes. This responsibility arises from a key rationale for conducting pragmatic trials: that they can facilitate uptake of their results by relevant decision-makers.

The open-access article was published this week in Learning Health Systems.

Much of the literature on posttrial responsibilities offers guidance on what is owed to research participants and broader communities at the conclusion of traditional explanatory clinical trials. Similar guidance is lacking for pragmatic trials.

The NIH Collaboratory researchers, led by Stephanie Morain of Johns Hopkins University, explore the distinct considerations that shape posttrial responsibilities in pragmatic trials. These include the responsibilities of the healthcare systems in which these trials are embedded, and decisions about implementation of interventions that show meaningful benefit after their integration into usual care settings, as well as deimplementation of those that do not.

Fulfilling this responsibility will require prospective planning by researchers, healthcare delivery system leaders, institutional review boards, and sponsors, so as to ensure that the knowledge gained from [pragmatic trials] does, in fact, influence real-world practice.

The article was coauthored by members of the NIH Collaboratory’s Ethics and Regulatory Core and Implementation Science Core, including Pearl O’Rourke, formerly of Partners HealthCare; Joseph Ali and Jeremy Sugarman of Johns Hopkins University; Vasiliki Rahimzadeh of the Baylor College of Medicine; and Devon Check and Hayden Bosworth of Duke University.

Read the full article.

 

January 3, 2024: Special Biostatistics Series Concludes With Missing Data in Cluster Randomized Trials

In this Friday's PCT Grand Rounds, Rui Wang of Harvard Medical School will offer the final session in our special series, Advances in the Design and Analysis of Pragmatic Clinical Trials, with "Methods for Handling Missing Data in Cluster Randomized Trials." The session will be held on Friday, January 5, at 1:00 pm eastern.

Wang is an associate professor of population medicine and the director of the Division of Biostatistics in the Department of Population Medicine at Harvard Medical School and the Harvard Pilgrim Health Care Institute. She is also an associate professor in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health. She is a longtime member of the NIH Pragmatic Trials Collaboratory's Biostatistics and Study Design Core Working Group.

This session's moderator, Fan Li, is an assistant professor of biostatistics at the Yale School of Public Health.

Join the online meeting.

This special Grand Rounds series includes moderated webinar discussions that bring together biostatisticians, clinical trials methodologists, and investigators to discuss challenges and share lessons learned in the design, implementation, and analysis of pragmatic trials. Download the series flyer and see the full schedule below, including archived webinar recordings and slides from previous sessions.

All sessions are free and open to the public. No registration is required.

December 13, 2023: In This Week’s PCT Grand Rounds, a Path Forward for Diversifying Clinical Trials

In this Friday's PCT Grand Rounds, Roxana Mehran of the Icahn School of Medicine at Mount Sinai will present "Diversifying Clinical Trials: A Path Forward."

The Grand Rounds session will be held on Friday, December 15, 2023, at 1:00 pm eastern.

Mehran is a professor of medicine and the director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Wiener Cardiovascular Institute at the Mount Sinai School of Medicine.

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October 25, 2023: In This Friday’s PCT Grand Rounds, Krumholz Presents PaxLC Trial of Paxlovid for Long COVID

Banner showing a headshot of Dr. Harlan Krumholz and the title of his upcoming PCT Grand Rounds Session, "Digital, Decentralized and Democratized: Lessons From The Yale PaxLC Trial."In this Friday’s PCT Grand Rounds, Harlan Krumholz of Yale University will present “Digital, Decentralized and Democratized: Lessons From the Yale PaxLC Trial.”

The Grand Rounds session will be held on Friday, October 27, 2023, at 1:00 pm eastern.

The PaxLC Trial is a decentralized study of Paxlovid in adult participants with long COVID. Krumholz, the principal investigator for the trial, is the Harold H. Hines, Jr Professor of Medicine at Yale University and the director of the Yale-New Haven Hospital Center for Outcomes Research and Evaluation.

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August 16, 2023: In This Friday’s PCT Grand Rounds, the Draft Revision of the ICH Good Clinical Practice Guideline

Headshots of Martin Landray, Khair ElZarrad, and Adrian Hernandez
From left: Martin Landray, Khair ElZarrad, and Adrian Hernandez

In this Friday’s PCT Grand Rounds, Martin Landray of the University of Oxford, Khair ElZarrad of the US Food and Drug Administration, and Adrian Hernandez of Duke University will present “Opportunities to Improve Clinical Trials: Draft Revision of the ICH Good Clinical Practice Guideline (E6[R3]).”

The Grand Rounds session will be held on Friday, August 18, 2023, at 1:00 pm eastern.

Landry is a professor of medicine and epidemiology at Oxford Population Health and deputy director of the University of Oxford’s Big Data Institute. ElZarrad is the director of the Office of Medical Policy in the FDA’s Center for Drug Evaluation and Research. Hernandez is a professor of medicine and vice dean of the Duke University School of Medicine and director of the Duke Clinical Research Institute, where he serves as co–principal investigator of the NIH Pragmatic Trials Collaboratory Coordinating Center.

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Grand Rounds June 30, 2023: Decentralized Trials – From Guidance to Reality & What’s Left (Adrian Hernandez, MD, MHS; Pamela Tenaerts, MD, MPH; Craig Lipset, MPH)

Speaker

Adrian Hernandez, MD, MHS
Director, Duke Clinical Research Institute

Pamela Tenaerts, MD, MPH
Chief Scientific Officer, Medable

Craig Lipset, MPH
Co-Chair, Decentralized Trials & Research Alliance

 

Keywords

Decentralized; Guidance; FDA; Clinical trials

 

Key Points

  • Decentralized clinical trials (DCTs) are regular clinical trials in which all activities take place at locations other than traditional trial sites. Over the past several years, a variety of factors have accelerated the need for decentralized trials, including the push to make trials more accessible, the increased speed of science, the possibility of environmentally conscious trials, and the need to be flexible in a rapidly changing world.
  • During the COVID-19 pandemic, several regulatory authorities around the world introduced guidance on DCTs. There has been a growing sense of hesitancy about whether regulators will remain equally receptive to these decentralized methods when the pandemic recedes. The Food and Drug Administration (FDA) issued a draft guidance in May 2023 that provided guidance about the conduct of decentralized clinical trials. This guidance and others in development in other markets act as an important countermeasure to ensuring sustained adoption and implementation of DCTs.
  • The FDA draft guidance includes guidance around rules and expectations for topics, including patient safety and data integrity, location stipulations, rules for health care providers, telehealth versus in-person protocol, digital health technology, trial operations, management and supervision, consent, and investigational product (IP) administration. Additional considerations are needed for the data management plan, monitoring plan, safety plan, task log, and case report forms in the FDA draft guidance.
  • The European Medicines Agency (EMA) released a separate guidance around DCTs in December 2022. While similar to the FDA draft guidance, the EMA guidance differs slightly in its emphasis and lack of certain topics. For instance, there is no discussion of the role of the health care provider in the DCTs, but it emphasizes the importance of patient voice. The EMA guidance also features an extensive discussion on the need for investigator oversight.
  • The key remaining issues for DCTs include clarification around the roles and responsibilities of health care providers as well as principal investigator (PI) oversight and responsibility. All trials are different, but it’s important to ask the right questions and be clear in the protocol.
  • As IRBs and ethics committees review of DCTs, they can use newly developed recommendations for what should be submitted and discussions that should occur once the appropriate documents are submitted.
  • DCTs are not only more convenient for trial participants, but they often provide a positive return on investment for the trial itself. The DCT space is evolving and will require more commentary on guidance, sharing research, and effective implementation.

Learn more

Read more about Decentralized Clinical Trials.

Discussion Themes

-As an early adopter of DCTs, could you share your experience and perspective on these issues? DCTs can make things easier for patients and the research more efficient. It can also contribute to providing more inclusive trials in solving some of the access issues that exist in healthcare and clinical trials. There are a lot of gray areas within the FDA guidance, but the key is to work together to address these challenges and ambiguities in order to ensure the safety and needs of the patients, while generating the knowledge necessary to further the trials.

-What is your response to questions surrounding the issue of adverse event reporting issue? A lot of questions on this topic have to do with the role of the health care provider as it relates to event reporting. The idea that health care providers in our communities may have data about an adverse event is not necessarily new, and health care providers are often aware of an adverse event very early on. Interstate licensing and our own institution’s policies are issues that still need to be addressed in terms of oversight and responsibilities. In some ways, health care providers are the same as any other data instrument in the trial – they are external data sources that come back to the investigator for safety and quality review.

Tags

#pctGR, @Collaboratory1

June 28, 2023: In This Week’s PCT Grand Rounds, What’s Left for Decentralized Clinical Trials?

Headshots of Adrian Hernandez, Pamela Tenaerts, and Craig LipsetIn this Friday’s PCT Grand Rounds, Adrian Hernandez, Pamela Tenaerts, and Craig Lipset will present “Decentralized Trials – From Guidance to Reality & What’s Left.”

The Grand Rounds session will be held on Friday, June 30, 2023, at 1:00 pm eastern.

Dr. Hernandez is a professor of medicine and director of the Duke Clinical Research Institute at Duke University; he is a co–principal investigator of the NIH Pragmatic Trials Collaboratory Coordinating Center. Dr. Tenaerts is the chief scientific officer of Medable, a cloud computing platform for decentralized clinical trials. Dr. Lipset is cochair of the Decentralized Trials & Research Alliance.

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May 31, 2023: PROACT Xa Pragmatic Trial to Be Featured in This Week’s PCT Grand Rounds

Headshot of Dr. John Alexander
Dr. John Alexander

In this Friday’s PCT Grand Rounds, John Alexander of Duke University will present “PROACT Xa and the Wizard of Oz: Behind the Curtain of a Pragmatic Decentralized Clinical Trial.” The Grand Rounds session will be held on Friday, June 2, 2023, at 1:00 pm eastern.

PROACT Xa was a prospective, randomized clinical trial conducted to determine whether apixaban was noninferior to warfarin in preventing valve thrombosis or valve-related thromboembolism in patients with an On-X mechanical aortic valve. The trial’s pragmatic design features enabled the investigators to conduct the the trial successfully during the COVID-19 public health emergency.

Dr. Alexander is a cardiologist and professor of medicine in the Duke University School of Medicine and a faculty member in the Duke Clinical Research Institute.

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April 19, 2023: MyTEMP Cluster Randomized Trial to Be Featured in This Week’s PCT Grand Rounds

Headshot of Dr. Amit GargIn this Friday’s PCT Grand Rounds, Amit Garg and Stephanie Dixon of Western University’s Schulich School of Medicine & Dentistry will present “Personalised Cooler Dialysate for Patients Receiving Maintenance Haemodialysis (MyTEMP): A Pragmatic, Cluster-Randomised Trial.” The Grand Rounds session will be held on Friday, April 21, 2023, at 1:00 pm eastern.

Dr. Garg is a professor of medicine, epidemiology, and biostatistics and the associate dean for clinical research in the Schulich School of Medicine & Dentistry. The MyTEMP trial is the first large, randomized trial to assess the effects of cooler dialysis fluid temperature on patient outcomes.

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March 29, 2023: This Friday’s PCT Grand Rounds Features Novel Approach to Lowering Blood Pressure in QUARTET USA Trial

Headshot of Dr. Jody CiolinoIn this Friday’s PCT Grand Rounds, Jody Cioliono will present “Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension (QUARTET USA): Results From a Randomized Controlled Trial.” The Grand Rounds session will be held on Friday, March 31, 2023, at 1:00 pm eastern.

The QUARTET USA trial tested a novel approach to lowering blood pressure compared with standard-dose monotherapy. The trial was embedded within a network of federally qualified healthcare centers in the Chicago metropolitan area. Ciolino is an associate professor of preventive medicine (biostatistics) and director of the master of science in biostatistics program in the Northwestern University Feinberg School of Medicine.

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