regulatory issues

April 24, 2024: Developments in Waivers and Alterations of Informed Consent in Minimal-Risk Research, in This Week’s PCT Grand Rounds

Posted on by Damon Seils

Dr. Lauren Milner, Dr. Jonathan Casey, and Dr. Matthew Semler

In this Friday's PCT Grand Rounds, Lauren Milner of the US Food and Drug Administration (FDA) and Jonathan Casey and Matthew Semler of Vanderbilt University will present "Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations – FDA Regulation Development and Research Landscape."

The Grand Rounds session will be held on Friday, April 26, 2024, at 1:00 pm eastern.

Milner is a regulatory policy adviser in the FDA's Office of Clinical Policy. Casey is an assistant professor of medicine and the director of the coordinating center for the Pragmatic Critical Care Research Group at Vanderbilt University Medical Center. Semler is an associate professor of medicine and codirector of the Vanderbilt Center for Learning Healthcare at Vanderbilt University Medical Center.

Join the online meeting.

January 31, 2024: Improving the Public’s Understanding of the FDA, in This Week’s PCT Grand Rounds

Posted on by Damon Seils

In this Friday's PCT Grand Rounds, Susan Winckler of the Reagan-Udall Foundation for the FDA will present "Strategies for Improving Public Understanding of FDA and the Products It Regulates: Why Should We Care, and What Might We Do?"

The Grand Rounds session will be held on Friday, February 2, 2024, at 1:00 pm eastern.

Winckler is the chief executive officer of the Reagan-Udall Foundation for the FDA, a nonprofit organization created by Congress “to advance the mission of the FDA to modernize medical, veterinary, food, food ingredient, and cosmetic product development, accelerate innovation, and enhance product safety.”

Join the online meeting.

January 25, 2024: Living Textbook Offers Pointers for Using an sIRB

Posted on by Damon Seils

The NIH Pragmatic Trials Collaboratory this week published a new chapter in its Living Textbook of Pragmatic Clinical Trials. Part of the Living Textbook’s new Ethics and Regulatory collection, the chapter discusses the logistics of using a single IRB (sIRB).

In 2016, the NIH issued a policy establishing the expectation that a “single IRB of record” will be used for all NIH-funded, multisite, human subjects research. The 2017 revision of the Common Rule likewise sets out a requirement for sIRB review of cooperative research.

The new chapter on sIRBs in the Living Textbook covers:

  • The process for setting up an sIRB
  • The responsibilities of “relying institutions”
  • Working with an sIRB while conducting research

Read more about the Living Textbook.

January 23, 2024: Ethics Consultation Documents Now Available for RAMP Trial

Posted on by Damon Seils

Ethics and regulatory onboarding documentation is now available for RAMP, one of the NIH Pragmatic Trials Collaboratory's newest pragmatic clinical trials. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the study.

The consultation took place by video conference and included representation from the study's principal investigator and study team, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

The goal of RAMP is to evaluate the use of a 12-week mind-body skills training program for patients with pain, including a one-on-one session with a “whole health coach” followed by 11 weekly group sessions to include prerecorded expert-led education videos, mind-body skills training and practice, and group discussions.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

January 16, 2024: Ethics Consultation Documents Now Available for AIM-CP and MOMs Chat & Care Study

Posted on by Damon Seils

Ethics and regulatory onboarding documentation for 2 of the NIH Pragmatic Trials Collaboratory's newest trials is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the AIM-CP trial and the MOMs Chat & Care Study.

The consultations took place by video conference and included representation from the studies' principal investigators, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

AIM-CP will address test a care management program to address inequities in access to nonpharmacological treatment for chronic pain in rural populations.

The MOMs Chat & Care Study will test the effectiveness of an integrated care model approach at 2 levels of intensity designed to facilitate timely, appropriate care for Black patients to reduce their risk for severe maternal morbidity.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

January 9, 2024: Ethics Consultation Documents Now Available for iPATH Trial

Posted on by Damon Seils

Ethics and regulatory onboarding documentation is now available for iPATH, one of the NIH Pragmatic Trials Collaboratory's newest pragmatic clinical trials. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the study.

The consultation took place by video conference and included representation from the study's principal investigator and study team, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

The goal of iPATH is to refine and implement an approach to practice transformation that was originally conceived and pilot-tested to support federally qualified health centers (FQHCs) in their pursuit of National Committee for Quality Assurance recognition as patient-centered medical homes for patients with type 2 diabetes. The study will include extensive qualitative work to identify implementation factors in FQHCs that are diverse in terms of geography, race/ethnicity, and diabetes control performance; and to customize and comprehensively evaluate the implementation approach.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

December 18, 2023: Ethics Consultation Documents Now Available for ARBOR-Telehealth and I CAN DO Surgical ACP

Posted on by Damon Seils

Ethics and regulatory onboarding documentation for 2 of the NIH Pragmatic Trials Collaboratory's newest trials is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the ARBOR-Telehealth and I CAN DO Surgical ACP studies.

The consultations took place by video conference and included representation from the studies' principal investigators, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel. Both projects are in their planning phase.

ARBOR-Telehealth will evaluate the use of a telehealth physical therapy strategy for patients who present to primary care clinics with low back pain in rural communities. A secondary aim of the study is to compare the effectiveness of the study's risk-stratification approach.

I CAN DO Surgical ACP will identify a system-based approach to help older adults undergoing elective surgery engage in advance care planning. The project will leverage the existing electronic health record and patient portal, PREPARE for Your Care materials to assist patients with completion of advance care planning, virtual healthcare navigators, and electronic nudges. Another goal of the study is to understand digital engagement, language, and social drivers of health that drive engagement in the intervention.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

October 10, 2023: Ethics Consultation Documents Now Available for BEST-ICU, Chat 4 Heart Health, and TAICHIKNEE

Posted on by Damon Seils

Ethics and regulatory onboarding documentation for the NIH Pragmatic Trials Collaboratory’s newest NIH Collaboratory Trials is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the BEST-ICU, Chat 4 Heart Health, and TAICHIKNEE studies.

The consultations took place by video conference and included representation from the studies’ principal investigators, members of the NIH Collaboratory’s Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel. All of the projects are in their 1-year planning phase.

BEST-ICU will explore the prevention of health impairments exacerbated by health disparities in the intensive care unit (ICU) through the application of the ABCDEF bundle, a multicomponent, evidence-based intervention to improve team-based care. The objective of the study is to evaluate 2 strategies grounded in behavioral economic theory and implementation science to increase ABCDEF bundle adoption and, in turn, address known health disparities in the ICU.

Chat 4 Heart Health will use a patient-level randomized pragmatic trial to test the comparative effectiveness of 3 text messaging delivery strategies that have been shown to improve individuals’ self-management health behaviors, including physical activity and medication adherence. The study findings will provide evidence regarding the best population-based strategy for universal delivery to engage all patients with health disparities in self-management to improve the American Heart Association’s “Life’s Essential 8” measures for improving and maintaining cardiovascular health.

TAICHIKNEE will compare the effects of web-based tai chi interventions versus routine care for individuals experiencing knee pain due to osteoarthritis. The practice of tai chi integrates physical, psychosocial, and behavioral components and has exhibited clinically significant improvements in chronic knee osteoarthritis pain conditions. The results of the study will inform widespread adoption of mind-body approaches for knee osteoarthritis, which affects more than 32.5 million individuals in the United States, across healthcare systems.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

August 17, 2023: American Journal of Bioethics Publishes Special Issue on Pragmatic Clinical Trials

Posted on by Karen Staman

A graphic that includes the cover image from the August 2023 issue of the American Journal of Bioethics. The text in the graphic reads as follows: "American Journal of Bioethics Special issue on pragmatic trials, featuring target articles from the NIH Pragmatic Trials Collaboratory."When research and clinical care are deliberately integrated in an embedded pragmatic clinical trial, the nature and extent of investigators’ obligations to patient-subjects are blurred, as is the clinician’s duty to participate is such research. To address these questions, the American Journal of Bioethics (AJOB) recently published commentaries on 2 target articles in a special issue on pragmatic clinical trials. Both of the target articles for the special issue are from the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core.

Target Article #1

Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research Is Embedded in Care by Stephanie Morain and Emily Largent

  • The authors challenge the notion that the current ethical model can simply be extended to pragmatic research. Instead, the authors suggest a shift to a model that better reflects the team- and institution-based nature of both clinical care and embedded research.

Target Article #2

Do Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? by Andrew Garland, Stephanie Morain, and Jeremy Sugarman

  • The authors argue that clinicians have a duty to participate in pragmatic research in usual care but suggest acceptable reasons to refuse, such as a badly designed trial, trial activities that violate the clinician’s conscience, or that the trial will impose excessive burdens on the clinician.

Some of the responses to the target articles are highlighted below.

Blurred Boundaries: Toward an Expanded Ethics of Research and Clinical Care
Megan C. Hailey and Nate Olson

  • The authors applaud the articles and offer a range of different research contexts where similar issues apply, including rare disease and genomics research.

Progressing From “Whether to” to “How to” Conduct Pragmatic Trials
Jonathan Casey, Todd Rice, and Matthew Smelner

  • The authors state that clinicians are confronted daily with clinical decisions where the best treatment is unknown and suggest that pragmatic trials are best situated to address the problem.

    “We believe that the US healthcare system has a basic choice to make: allow arbitrary variation in clinical care and continue to systematically expose patients to suboptimal or harmful therapies indefinitely or structure that variation through pragmatic trials to generate knowledge, reduce variation, and improve outcomes over time.”

Ethical Pragmatic Clinical Trials Require the Virtue of Cultivated Uneasiness
Joel Pacyna and Jon Tilburt

  • The authors suggest that softening the default requirement of documenting individual consent removes a primary tool that researchers rely on to ensure the ethical nature of their research. Cultivated uneasiness about waiving consent is warranted and will push researchers to fully examine their decisions and subsequent consequences.

Distinguishing Clinical and Research Risks in Pragmatic Clinical Trials: The Need for Further Stakeholder Engagement
Benjamin S. Wilfond, Sinem Toraman Turk, Stephanie A. Kraft, Elliott M. Weiss, Philip I. Tarr, David Schnadower, and Stephen B. Freedman

  • The authors present a case study involving complex interventions to support the target articles’ supposition that ethical frameworks for pragmatic clinical trials need to account for shortcomings in clinical care.

More-Than-Partial Entrustment in Pragmatic Clinical Trials
Henry S. Richardson

  • The author strongly supports the obligations of the investigators to report significant, actionable incidental findings about individuals.

End-to-End Integration of Pragmatic Trials Into Health Care Settings
Sarah M. Greene

  • The author agrees that pragmatic trials will provide invaluable evidence, but argues that trialists must take care not to interrupt the flow of clinical practice.

For more, see the 15 other commentaries in the special issue of AJOB and the Living Textbook chapter on Consent, Waiver of Consent, and Notification.

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)

Posted on by Lauren Stewart

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