ethics

March 26, 2021: The Path to Preventive Genomics (Robert C. Green, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Robert C. Green, MD, MPH
Professor of Medicine (Genetics), Harvard Medical School
Director, Genomes2People Research Program and Preventive Genomics Clinic
Mass General Brigham, Ariadne Labs, Broad Institute

Topic

The Path to Preventive Genomics

Keywords

Preventive genomics; Whole genome sequencing; Return of results; Risk stratification; Precision medicine

Key Points

  • The goal of the Genomes2People research program is to bring genomics into evidence-based patient care. The program conducts empirical research in translating genomics into health, including the first rigorous trials to provide comprehensive genome sequencing to adults and newborn infants.
  • Twenty percent of healthy people are carrying a monogenic disease risk variant. The number of people carrying variants for monogenic diseases depends on how many genes are analyzed.
  • Polygenic risk is the chance of developing certain health conditions based on a large number of genetic variants across the genome.

Discussion Themes

People are interested in medical information about themselves. It’s up to the healthcare system and physicians to create nuanced communication about genetic information that helps people understand its role in health.

Is there a diversity of families seeking out genomic screening services?

Should genetic variants of unknown significance (VUS) be reported to the individual?

Read more at Genomes2People and Brigham Preventive Genomics Clinic.

Tags

#pctGR, @Collaboratory1, @genomes2people

March 29, 2021: New Resources from the Health Care Systems Interactions Core

Posted on by Karen Staman

The Health Care Systems (HCS) Interactions Core of the NIH Collaboratory has created a new guidance document: Resources for Frequently Asked Questions. The document compiles common questions from researchers and points to resources that provide potential solutions, including Living Textbook chapters and journal articles. The topics include evaluation strategies, anticipating and adapting to changes, dissemination and implementation, and stakeholder engagement.

The NIH Collaboratory Core Working Groups have created a series of handouts to help investigators conduct pragmatic trials:

March 5, 2021: Data and Safety Monitoring Boards for Trials of COVID-19 Vaccines: The Challenges (Susan S. Ellenberg, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Susan S. Ellenberg, PhD
Professor of Biostatistics, Medical Ethics, and Health Policy
Perelman School of Medicine
University of Pennsylvania

Topic

Data and Safety Monitoring Boards for Trials of COVID-19 Vaccines: The Challenges

Keywords

COVID-19; Data Monitoring Committee (DMC); Data and Safety Monitoring Board (DSMB); Pandemic; Vaccine trials; Monitoring boundaries; Safety and efficacy; NIH

Key Points

  • With COVID-19, everyone, globally, is an “affected community.” This brings a strong sense of urgency for DSMBs.
  • Several COVID-19 vaccine candidates are studied under the NIH umbrella. A single DSMB, constituted in mid-2020, oversees all these COVID-19 trials and reports to that trial’s Oversight Group.
  • Subgroup issues have been important in COVID-19 vaccine trials. The DSMB monitors carefully for representation of subgroups of interest in trial participants, including those over age 65, Black, Hispanic, and participants with comorbidities that may predispose them to more serious disease.

Discussion Themes

Has there been pressure to prematurely discontinue any of the COVID-19 vaccine trials?

How accurate is the post-vaccine data being collected—especially since these vaccines have only emergency use authorization?

What are your thoughts on future trial design if we have another pandemic?

See more COVID-19 resources for researchers and access other webinars in the COVID-19 Grand Rounds series on the Collaboratory’s COVID-19 resource page. Read more about data and safety monitoring in the Living Textbook.

Tags

#pctGR, @Collaboratory1

March 2, 2021: Grand Rounds Continues With Challenges of DSMBs in COVID-19 Vaccine Trials

Posted on by Damon Seils

Prof. Susan EllenbergIn this week’s COVID-19 Grand Rounds session, Dr. Susan Ellenberg of the University of Pennsylvania, will present “Data and Safety Monitoring Boards for Trials of COVID-19 Vaccines: The Challenges.” The Grand Rounds session will be held on Friday, March 5, at 1:00 pm eastern. Join the online meeting.

The NIH Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency.

For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

February 8, 2021: Meeting Minutes are Available from the Ethics and Regulatory Core Discussions with the PRISM NIH Collaboratory Trials

Posted on by Gina Uhlenbrauck

Meeting minutes, supplementary materials, and updates are available that summarize recent discussions related to the ethics and regulatory issues associated with the six 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.

September 22, 2020: New Article Highlights Ethical and Regulatory Challenges of Conducting PCTs

Posted on by Gina Uhlenbrauck

Cover of Ethics & Human ResearchA recent article in Ethics & Human Research describes the experience and management of regulatory noncompliance during the conduct of a large, multisite embedded pragmatic clinical trial (ePCT). The Trauma Survivors Outcomes and Support (TSOS), an NIH Collaboratory Trial, was a stepped-wedge, cluster-randomized clinical trial of a collaborative care intervention for injured patients with symptoms of posttraumatic stress disorder in 25 level 1 trauma centers in the United States. The article, Ethical and Regulatory Concerns in Pragmatic Clinical Trial Monitoring and Oversight, was coauthored by members of the TSOS study team, the Collaboratory’s Ethics and Regulatory Core, and colleagues.

The authors describe how the study encountered variabilities in participant tracking across sites, which led to a study-wide internal audit and corrective action. The study team implemented a revision of the participant tracking system and retrained site staff in new procedures. Based on the lessons learned, the authors offer recommendations for future PCTs and relevant stakeholders, including institutional review boards, data safety and monitoring boards, institutions, and trial sponsors.

Among the recommendations:

  • Use a single IRB of record to streamline regulatory processes and reduce variability among research sites.
  • Standardize research procedures but allow for real-world flexibility; this could include real-time, workflow-integrated study logging that captures and documents provider turnover and regulatory training compliance.
  • Implement thorough, specific, and practical training in procedures, especially around participant enrollment and tracking.
  • Ensure that research procedures, monitoring and oversight plans, and training are study specific to account for unique issues, contexts, and needs.

Thoughtful planning, communication, and development and dissemination of standardized procedures remain hallmarks of successful research operations both to advance biomedical research and to ensure appropriate safeguards for its participants. –Roberts et al.

September 1, 2020: New Publication Explores Stakeholder Perspectives on Collateral Findings in Pragmatic Clinical Trials

Posted on by Gina Uhlenbrauck

A recent article in Learning Health Systems from members of the NIH Collaboratory’s Ethics and Regulatory Core and colleagues describes key themes from stakeholder interviews about collateral findings in pragmatic clinical trials (PCTs). A collateral finding is information that emerges in a PCT that is unrelated to the primary research question but which may have implications for patients, clinicians, and health systems.

The authors conducted semi-structured interviews with 41 key stakeholders experienced in the conduct or oversight of PCTs and those in health system leadership. The interviews explored respondents’ experience with collateral findings in PCTs and their reactions to how such findings should be managed. The authors identified four themes that emerged from the responses:

  • Collateral findings are complicated by layers of ambiguity about the nature of PCTs and how to characterize unanticipated results.
  • No one-size-fits-all approach exists to managing collateral findings in PCTs, as such findings are context-specific.
  • There is a range of attitudes regarding the scope of research responsibilities and obligations in PCTs.
  • While prospective planning for collateral findings in PCTs is critical, such planning has not yet been widely undertaken.

The article provides additional details on each theme, including excerpts from stakeholder responses that show a range of insights for managing unanticipated findings in PCTs. A clear takeaway is that prospective planning is an essential step in addressing the ethical management of collateral findings to inform the future conduct of PCTs.

The expansion of PCTs makes it likely healthcare systems will increasingly encounter [collateral findings], yet little guidance exists regarding their appropriate management. – Morain et al. 2020

This work was supported within the National Institutes of Health (NIH) Health Care Systems Research Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Supplemental funding for this work was provided by the National Center for Complementary and Integrative Health. The aim of the supplement, Management of Trial Incidental Findings Study (MOTIFS), is to develop an empirically informed, ethically sound approach to managing incidental findings in PCTs.

August 26, 2020: New Publication on Patients’ Views About Disclosure of Collateral Findings in Pragmatic Clinical Trials

Posted on by Gina Uhlenbrauck

Members of the NIH Collaboratory’s Ethics and Regulatory Core, and colleagues, recently published an article in the Journal of General Internal Medicine highlighting potential challenges in managing collateral findings in pragmatic clinical trials (PCTs). A collateral finding is information that emerges in a PCT that is unrelated to the primary research question but which may have implications for patients, clinicians, and health systems.

In their study, the authors presented focus group participants with a hypothetical scenario, asking them to imagine they were a patient in a PCT wherein it was discovered incidentally that they were taking two contraindicated medications. The authors then explored participants’ reactions to the discovery and their preferences for whether or not they would want to be informed about the collateral finding, how it should be communicated and by whom, and the type and amount of information that should be communicated.

The article provides excerpts from participants’ reactions—which varied across the spectrum from fear and anger to gratitude. Their preferences for how to disclose collateral findings in PCTs also suggest several important considerations for clinicians, including the expectation that patients will question them about such findings, and how to develop approaches for disclosure that align with patients’ values.

Preferences for how such disclosures are made varied but were driven by several consistent desires, namely minimizing patient harm and anxiety and demonstrating trust and respect. – Bollinger et al 2020

This work was supported within the National Institutes of Health (NIH) Health Care Systems Research Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Supplemental funding for this work was provided by the National Center for Complementary and Integrative Health. The aim of the supplement, Management of Trial Incidental Findings Study (MOTIFS), is to develop an empirically informed, ethically sound approach to managing incidental findings in PCTs.

July 16, 2020: New Publication Describes Unexpected Complications of Certificates of Confidentiality for Pragmatic Clinical Trials

Posted on by Gina Uhlenbrauck

Judith Carrithers and Jeremy Sugarman, co-chairs of the NIH Collaboratory’s Ethics and Regulatory Core, recently published an article in the journal Learning Health Systems that examines the NIH’s Certificate of Confidentiality (CoC) policy for NIH-funded human subjects research. Since October 1, 2017, the CoC is issued automatically and applies to all biomedical, behavioral, clinical, and other research funded wholly or in part by the NIH that “collects or uses identifiable sensitive information.”

In their review of the CoC policy, the authors describe unanticipated challenges of applying the policy to pragmatic clinical trials, where the focus is on embedding research interventions in clinical care and which relies on existing data in electronic health records (EHRs). The authors identify 3 issues that are especially problematic in embedded pragmatic clinical trial (ePCT) settings and which may jeopardize the progress of learning health systems:

  • Whether the EHR may be populated with research data that may be sensitive or stigmatizing without explicit consent from subjects
  • Incomplete protections for sensitive data in the EHR
  • Requirements for notifying subjects about the policy’s provisions

The authors urge the NIH to provide formal guidance on the CoC policy as it pertains to ePCTs. Read the full publication online.

“Special attention should be paid to pragmatic research that populates the electronic health record with research data as well as research conducted without explicit consent.” – Sugarman and Carrithers