Focus Area: Clinical Trials & Research

Global Representation: An Introduction to the Global Representation Project

Introduction


The MRCT Center’s Achieving Diversity, Inclusion, and Equity in Clinical Research Guidance Document, released in late 2020 and updated in 2021, outlines a principled, multi-stakeholder approach to optimize the inclusion of diverse populations in clinical research. It is accompanied by a Toolkit, including checklists, logic models and case studies, an Equity by Design metrics framework, and resources to support ethics committees. These are all living documents, and further work, such as the inclusion of people with disabilities in clinical research, is ongoing.

As part of this further work, the MRCT Center has widened our DEI lens from domestic to Global Representation. Over the last nine months, we have collaboratively sought to better understand how concerns around diversity, equity, and inclusion in clinical research are understood and prioritized in different countries and regions around the world and what this means for the many stakeholders involved in research conducted in multi-country contexts. We have several tools under development, including a draft Roadmap (prompts for developing a global diversity, equity, inclusion, and accessibility strategy) introduced during the [invite-only] Executive and Steering Committees meeting in December and a Diversity Action Plan (DAP) tool presented at the MRCT Annual Meeting.  

The primary objectives of this project encompass a comprehensive exploration of DEI challenges within the domain of global clinical research. These objectives are two-fold.

  1. The project is focused on a deeper comprehension of DEI issues in clinical research on a global scale. This entails seeking insights from key stakeholders such as sponsors, regulators, ethics committees, health departments, Principal Investigators (PIs), study sites, and research participants.
  2. The project is working on enhancing and expanding the existing resources and tools provided by the MRCT Center to incorporate these broader perspectives. This expansion includes supporting DEI in research endeavors within individual countries and, notably, in multi-country studies.

The preliminary scoping of the first objective has brought to light several areas of focus encompassing: the recognition that different dimensions of diversity hold varying degrees of relevance in diverse global contexts; the challenges of categorizing diversity facets like race, ethnicity, and social determinants of health in ways that remain contextually meaningful in various countries; ethical concerns related to incentivizing the participation of groups traditionally viewed as ‘vulnerable’ in research, along with associated risks of exploitation; divergent approaches of regulators worldwide regarding diversified participation in research, both in terms of licensing requirements and the endorsement of best practices; and varying motivations for addressing DEI at a global level, ranging from ethical considerations regarding broader generalizability and global access to interventions to more immediate needs for compliance with regulatory mandates in different regions.

In essence, the project seeks to synthesize these multifaceted elements into a unified strategy that addresses DEI challenges in the global clinical research landscape.

We have been drafting four principal tools:

  • A Draft Roadmap: Prompts for Developing a global diversity, equity, inclusion, and accessibility (DEI) strategy
  • Embedding Ethical Considerations related to global DEI
  • Working with Partner Countries to Strengthen Research Capacity
  • Diversity Action Plan (DAP) Template

If you would like to share relevant resources or insights, please contact us here.

Real World Evidence (RWE) and Emerging Trends in Clinical Trial Subject Recruitment

May 3, 2024 @ 1:30 pm – 4:00 pm

Hybrid: In-person (Boston) and Virtual (Zoom)

800 Boylston St.
Boston, MA 02199

Meeting of The Research, Development, and Regulatory Roundtable (R3). Meetings are open to R3 Sponsors. To learn more about how to become an R3 Sponsor, click here.

Topics:

  • Recent Developments in FDA Guidance on Real World Evidence
  • Subject-Directed Recruitment Materials and Testimonials

Abstract: Real World Evidence and Emerging Trends in Clinical Trial Subject Recruitment

Real World Evidence

In recent years, real-world evidence (“RWE”) has increasingly been incorporated into product development programs, spurred by greater access to RWE, legislative changes, and significant policy development at FDA. The use of RWE raises novel opportunities, as well as new challenges for regulators, clinical trial sponsors, and the life sciences and healthcare industry to set common standards for RWE to ensure it can be relied upon with confidence in regulatory decision-making.  

During 2023, FDA released two draft and three final guidance documents concerning RWE.  These included the following:

  •  Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products (Draft, February 2023)
  • Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products (Final, August 2023)
  • Use of Real-World Evidence to Support Regulatory Decision-Marking for Medical Devices (Draft, December 2023)
  • Data Standards for Drug and Biological Product Submissions Containing Real World Data (Final, December 2023)
  • Real-World Data:  Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products (Final, December 2023) 

This session will provide an overview of key concepts from these guidance documents, focusing in particular on how they intersect with FDA’s existing regulations on clinical investigations and how they may change the regulatory landscape.  In addition to focusing on these recent FDA guidance documents, the speakers will address the application of other U.S. regulatory regimes to RWE activities, including the Common Rule, the Information Blocking Rule, and HIPAA and other data privacy laws.

Clinical Trial Subject Recruitment Trends

Clinical trial sponsors are increasingly exploring different techniques to attract potential subjects to clinical trials, particularly in the context of rare disease studies for which subjects may be difficult to find.  These techniques have included the following:

  •  Use of testimonials featuring active clinical trial subjects in clinical trial advertisements
  •  Inclusion of detailed scientific information gathered in pre-clinical or Phase 1 studies in subject-directed recruitment materials
  • Partnerships with electronic health record vendors to identify potential trial sites or subjects

Each of these techniques raise novel regulatory questions, including concerns about pre-approval promotion, data bias, need for institutional review board review and approval, and data privacy.  

This session will analyze these trends and the attendant regulatory considerations for each.

Gene Therapies: Probing the Ethics

Meeting Summary

Presented on: December 14, 2023

Presented at: Cambridge, MA and online

The MRCT Center recently initiated a project on cell and gene therapies (CGTs), led by Carolyn Riley Chapman, PhD MS, Lead Investigator in the Division of Global Health Equity at Brigham and Women’s Hospital and Member of the Faculty at Harvard Medical School. In collaboration with diverse stakeholders, the project will identify and characterize the unique ethical, regulatory, and logistical challenges related to CGT research and development; we will then develop potential solutions or approaches to help address those issues.  This meeting, held in conjunction with the Bioethics Collaborative, served, in part, as the project launch.

While the MRCT Center Bioethics Collaborative meetings are usually open only to invited guests and individuals from the organizations that sponsor the forum, this session was presented in conjunction with the 2023 MRCT Center Annual Meeting and was open to the public.

2023-12-14 BC summary FINAL

Related Resources

Cell and Gene Therapies

Cell and Gene Therapies

There is justified excitement about the emergence and potential of cell and gene therapies (CGT): a number of CGTs have recently received market approval and hundreds more are in preclinical and/or clinical development. As a new therapeutic class, there is still much to learn about the benefits and risks of CGT, necessitating complex decision-making and long-term follow-up in many trials. Many CGTs also have complex manufacturing and/or supply chain challenges. For these reasons and because of the need for specialized clinical expertise, trial sites are often geographically limited. The CGT project aims first to ascertain and characterize the ethical, regulatory, and logistical issues that are arising in the specific context of CGT research and development. We will then work to address and mitigate these challenges through a collaborative, multi-stakeholder approach.

OBJECTIVES

  • Identify and characterize ethical, regulatory, and logistical challenges arising in the context of global research and development of cell and gene therapies.
  • Employ a multi-stakeholder approach to co-develop actionable and practical mechanisms for addressing these challenges to support efficient, safe, and respectful clinical development of CGT products.

KeY MILESTONES

project Leadership & sTAFF

  • Carolyn Riley Chapman, PhD MS, MRCT Center. Lead Investigator, Brigham and Women’s Hospital and Member of the Faculty, Harvard Medical School.
  • Barbara E. Bierer, MD, Faculty Director, MRCT Center.
  • Sarah White, MPH, Executive Director, MRCT Center.
  • Emina Berbic, Program Manager, MRCT Center

Project Resources

  • Tools

November 4, 2025

Toolkit for Supporting the Design, Conduct, and Reporting of Long-Term Follow-Up Studies for Gene Therapies ›
  • Webinar

November 4, 2025

Long-Term Follow-Up for Gene Therapies: Toolkit Release ›
  • Publication

October 22, 2025

Characteristics of long-term follow-up studies for gene therapies registered on ClinicalTrials.gov ›
  • Webinar

June 26, 2025

Patient-Centered Long-Term Follow-Up for Gene Therapies ›
  • Publication

May 15, 2025

Patient-centered long-term follow-up for gene therapies aligns with ethics and science ›
  • Webinar

May 6, 2025

Innovative Approaches for Gene Therapy Long-Term Follow-Up ›
  • Publication

March 11, 2025

Wanted, but Elusive: Clear Solutions for Addressing Potential Group Harm in Data-Centric Research ›
  • Publication

December 21, 2024

Toward Justice and Community Empowerment in Genomics Studies on Sensitive Traits ›
  • Webinar

December 5, 2024

What’s Up with Long-Term Follow-Up: Ethical, Regulatory, & Operational Challenges ›
  • Meeting Summary

February 14, 2024

Gene Therapies: Probing the Ethics ›
  • Publication

November 27, 2023

Consideration and Disclosure of Group Risks in Genomics and Other Data-Centric Research: Does the Common Rule Need Revision? ›

Promoting Global Clinical Research in Children – A Project Overview

We are delighted to announce the launch of an interactive webpage dedicated to our Promoting Global Clinical Research in Children project. With our workgroup activities now complete, we are focused on presenting our findings and actively engaging in international projects. We offer a comprehensive suite of resources tailored for stakeholders who are directly involved or have an interest in pediatric clinical research.

Please visit this interactive summary page or the Promoting Global Clinical Research in Children project page for tools, publications, and materials supporting pediatric clinical research worldwide.

 

Is It Time to Retire the Concept of Deidentification?

December 12, 2024 @ 9:00 am – 11:30 am

Virtual Event

In the US, research with data only qualifies as human subjects research and triggers protections, such as ethics board review and informed consent, when those data are identifiable, defined as “information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information” (45 CFR 46.102(e)(5)). The process of deidentification of data involves removing explicit identifiers such that the data cannot be readily linked to an individual; deidentified data is no longer considered protected health information subject to the protections of the Privacy Rule, implemented in response to the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”). Deidentified data, therefore, can be used without consent, without review by an IRB or ethics committee, and without oversight by a Privacy Board.

In the approximately 30 years since the passage of HIPAA and even in the 5 years since the issuance of the Common Rule, technology has advanced. The concept of deidentification may no longer be relevant. Numerous studies have demonstrated that it is relatively easy to re-identify individuals from seemingly deidentified data sets, particularly when these data are triangulated with publicly available data sources. The increasing use and sophistication of Artificial Intelligence (AI) further exacerbates this situation, raising questions about whether any types of data are beyond re-identification or fail to meet the regulatory definition of “identifiable.” Other countries (e.g., EU/EEA, China, India, and others) and even US States (e.g., California) have adopted this position and, unlike the US, have substantiated data protections and personal rights to privacy through the law.

Eliminating the concept of deidentification[1] (a concept that the HHS Office of Human Research Protections promises to review periodically) would have profound effects on clinical research, including impact on IT infrastructure, data repositories, secondary use of data, consent paradigms, and scientific discovery. But given the current ease of reidentification, might it be time to retire the concept of deidentification in the service of privacy, autonomy, and respect for persons?

[1] The HHS Office of Human Research Protections promises to review the concept of identifiability periodically, although that has not yet occurred in the five years since the effective date of the 2019 Final Common Rule. If OHRP changes its definition, FDA is likely to reconsider its interpretation of identifiability. 

 This meeting is open to sponsors of the Bioethics Collaborative. For more information about the Bioethics Collaborative and how to become a sponsor, click here.

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Impact of Dobbs on Reproductive Health: Unintended Consequences for/on Research 

September 10, 2024 @ 10:00 am – 12:30 pm

Hybrid: In-person (Boston) and Virtual (Zoom)

800 Boylston St.
Boston, MA 02199

Topic: Impact of Dobbs on Reproductive Health: Unintended Consequences for/on Research 

In 2022, the United States Supreme Court ruled, in Dobbs vs. Jackson Women’s Health Organization, against a federal right to abortion. The effects of this ruling continue to reverberate across the research ecosystem. Clinical trials often involve the administration of investigational therapies that pose reproductive risks. Because of this, participants are routinely asked to undertake measures that could pose privacy risks to them in states where elective termination of pregnancy is illegal. These measures include documentation of the results of pregnancy tests and reporting of incidental pregnancies and their outcome, among others. These risks may also extend to site staff in states where providers are prohibited from advising or facilitating elective termination of pregnancy. In addition, research on various aspects of pregnancy is itself at risk of being stifled for similar reasons. What should the research community’s response be to this situation? Is there an obligation to educate participants about these risks as part of the informed consent process? Who should bear this responsibility? What mechanisms are available to help shield participants and other stakeholders from undue risk while permitting the collection of important pregnancy data? To what extent, if any, do Certificates of Confidentiality provide sufficient legal protections? Will this ruling impact innovation in reproductive health research in the US more generally? At the next Bioethics Collaborative, we will focus on these and other questions related to the ongoing effects of the Dobbs rulingon clinical research. 

This meeting is open to sponsors of the Bioethics Collaborative. For more information about the Bioethics Collaborative and how to become a sponsor, click here.

Reciprocity in Research: Does Justice Support Community Investment?

June 18, 2024 @ 9:30 am – 12:00 pm

Virtual Event

Topic: Reciprocity in Research: Does Justice Support Community Investment?

Abstract:  It is generally agreed that sponsors and other entities undertaking research in limited-resource settings incur certain duties of reciprocity. These obligations ensure that host communities are treated fairly and not exploited, given the burdens and risks of research undertaken by community members. However, the expectations, content, and limitations of these obligations are not defined. The next Bioethics Collaborative will be devoted to understanding and assessing different approaches to satisfying the ethical contorts of reciprocity for research undertaken in these settings.

Click here to view the Meeting Summary.

2024-07-16 June BC Meeting Summary_FinalDownload

This meeting is open to sponsors of the Bioethics Collaborative.

For more information about the Bioethics Collaborative and how to become a sponsor, click here.