Executive Committee Portal

Executive Committee Portal

This portal is for Executive Committee sponsors of the MRCT Center. Information shared here is confidential and should not be shared without express permission. Please contact Sarah White with any questions.

  • September 10: Bioethics Collaborative. Topic: Impact of Dobbs on Reproductive Health: Unintended Consequences for/on Research
  • September 17: Executive & Steering Committees (EC/SC)
  • October 10: Research, Development, and Regulatory Roundtable (R3) Topic: (1) Laboratory Developed Tests; (2) Limitations on Sharing Data with China and Other Countries of Concern
  • October 22: Executive Committee (EC)
  • November 13: Executive & Steering Committees (EC/SC) and Dinner
  • November 14: MRCT Center Annual Conference
  • November 15: MRCT/Vivli Meeting

Deliverables in Flight: Seeking Review

As one perk of MRCT Center sponsorship, we are offering you the opportunity for a sneak-peek at final draft MRCT Center tools before public release. We will post the documents, by MRCT Center project, that you may choose to review. The dates of the review period (generally 2-4 weeks) and the contact person for questions/response will be listed for each, depending upon the project. Where applicable, we will provide a list of EC/SC member organization staff that have contributed to the draft tools, to assist with internal dialogue. Please note, all documents posted to the EC/SC portal are in draft form, and we ask that you do not share them beyond your review teams. All returned EC/SC comments and edits will be de-identified and shared with the working group prior to product finalization. We look forward to any feedback that you choose to share.


Post-Trial Responsibilities (PTR): Continued Access to an Investigational Product

In 2017, the MRCT Center released a framework that outlined the post-trial responsibilities of a research participant at the end of participation in a clinical trial. The framework included principles, a guidance document, and toolkit and provided a case-based, stakeholder approach to evaluate ethical responsibilities for continued access to an investigational product. Since February 2023, the MRCT Center has met monthly with a task force to identify and develop updated tools and resources. Our work includes a revised set of principles with associated analysis and a framework of responsibility for continued access to investigational products.

The Principles of Post-Trial Responsibilities: Continued Access to an Investigational Product are 12 principles and their corresponding analysis, which guide the ethical responsibilities and actions to provide continued access to an investigational product at the conclusion of a patient’s participation in a clinical trial. The Post-trial, Continued Access Responsibilities to Investigational Products Framework: Scenarios that require further consideration comprise 5 milestones, specific scenarios, and considerations that organizations can utilize to make equitable and fair decisions related to continued access to an investigational product.

The MRCT Center PTR team requests review and feedback from interested EC/SC members on both documents.

The MRCT Center asks that EC/SC members not share these resources externally at this time. They are provided as Word documents to be more convenient to edit and provide feedback. Comments can be emailed to Sarah (sawhite@bwh.harvard.edu). Please let us know if you have any questions. Thank you for taking the time to review.

Recent and Upcoming submissions for public comment

Details:

The Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center) is pleased to provide an update on our most recent efforts to shape public policies that affect clinical research.

June 2024 Public Comment Submissions

June 25: We responded to a series of three FDA draft guidance documents addressing eligibility criteria for U.S.-based cancer clinical trials. For all three documents, we were supportive of the efforts the FDA has taken to make clinical trials more representative of the intended post-approval patient population. We encouraged additional clarity and granularity with regard to operationalizing these draft guidelines, in advance of their final issuance. Further, we agreed that eligibility criteria should be carefully considered, caution against copying and pasting eligibility criteria from the protocol of one study into the draft protocol of a new study, and advocate that exclusion criteria should be clearly justified based on safety or ethical reasons.

  • (FDA-2024-D-1402) Specific to the first draft guidance of the series, (i)Cancer Clinical Trial Eligibility Criteria: Laboratory Values,” we stated in our public comment submission that the MRCT Center agrees with the FDA that overly restrictive laboratory value-based eligibility criteria are problematic and that such criteria may well exclude the very cancer patients that may benefit from the treatment under study, particularly when the malignancy (or its prior treatment) is affecting those lab values. The MRCT Center also asked for more specific examples of how to describe the potential variation of lab values (e.g., by race) and any additional/confirmatory testing needed in the eligibility criteria so as to better support a position of inclusion-by-default and exclusion-only-when-necessary.
  • (FDA-2024-D-1377). The main takeaway from the public comments that we submitted on the second guidance in the series (ii) “Cancer Clinical Trial Eligibility Criteria: Performance Status is that we took a strong stance against using Performance Status as an eligibility criterion at all. The measures of performance status commonly used across cancer trial eligibility criteria, the Karnofsky Performance Status Score  (first developed in 1948) and ECOG Performance Status Scale (first developed in 1960), are outdated and highly subjective constructs. Their use as a proxy for disease progression in cancer trial eligibility criteria conflates illness with disability, and results in the discriminatory exclusion of many people with disabilities, which is counter to Section 504 of the Rehabilitation Act, Titles II or III of the Americans with Disabilities Act, and Section 1557 of the Affordable Care Act. We encourage the FDA to adopt alternative measures that more appropriately reflect both the clinical risks (assessed by laboratory and diagnostic testing) and the individual participant’s experience and preferences.
  • (FDA-2024-D-1376). Our public comments on the third guidance (iii)Cancer Clinical Trial Eligibility Criteria: Washout Periods and Concomitant Medications,” asked the FDA to clarify its use of the term “medication,” whether either the recommendations regarding concomitant medications or the washout period differ in the case of early (Phase 1/2a) versus late (Phase 3 and post-approval) trials, and when additional data and sub-studies might be needed to understand potential drug-drug interactions when participants are taking concomitant medications for chronic conditions.

June 24: The MRCT Center submitted public comments in response to the World Medical Association’s (WMA’s) second phase of proposed revisions to the Declaration of Helsinki (DoH). Mark Barnes, MRCT Center Faculty Co-Director, attended the last working meeting on the DoH. In direct response to concerns discussed internally and with our Executive and Steering Committees, we recommended substantial revisions to the WMA Workgroup’s proposals, including recommending comments specific to vulnerable populations, research ethics committees, informed consent, and post-trial access. Both Mark Barnes and Barbara Bierer have been invited to attend the final WMA revision discussion meeting in Washington, D.C. this August.


June 20: (FDA–2023–D–5470):  FDA continued its guidance series on RWE, issuing “Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products.” In support of the guidance, the MRCT Center submitted public comments requesting further development of FDA’s concerns that are unique to RWE-based studies and the cross-referencing of the current guidance to specific sections of other RWE guidance documents to streamline the end-user experience.


June 18: (NOT-OD-24-112). The MRCT Center submitted public comments on a proposed glossary of innovative clinical research terms published jointly by FDA and NIH, “FDA-NIH Terminology for Clinical Research.” We encouraged clarification of the scope and intended audience of the draft glossary and recommended additional terms for inclusion in the final version. The FDA-NIH glossary will complement the MRCT Center’s Clinical Research Glossary efforts.


April 2024 Public Comment Submissions

We submitted comments on three draft guidance documents from the U.S. Food and Drug Administration (FDA):

April 30: We responded to the FDA draft guidance entitled “Key Information and Facilitating Understanding in Informed Consent: Guidance for Sponsors, Investigators, and Institutional Review Boards” (FDA-2022-D-2997).

Overall, we were encouraged by the FDA’s efforts to harmonize informed consent regulations and guidance with those of the federal Office for Human Research Protections (OHRP), the flexibilities incorporated into the guidance regarding informed consent forms (ICFs), and the FDA’s emphasis on employing plain language throughout the informed consent process. However, we offered several suggestions for strengthening the guidance and provided specific comments on both the main text of the guidance and the hypothetical models included in the appendix. These comments were highlighted by the Regulatory Affairs Professionals Society after the comment period closed.


April 29: We submitted a formal response to the FDA draft guidance document, “Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products” (FDA-2016-D-3561).

During a recent meeting of the Executive and Steering Committees, it was noted that this document was drafted to comply with the requirements of Statistical Policy Directive #15 (SPD 15) from the U.S. Office of Management and Budget (OMB), which has since become obsolete. Since the FDA first published this guidance document, OMB formally updated SPD 15. While the FDA has already acknowledged that this draft guidance must be heavily revised to comply with the new OMB requirements, the MRCT Center took the opportunity to comment on areas of general concern. In our response, we:

  • Requested clarification on the FDA’s expectations for how sponsors will use race and ethnicity data in shaping their clinical research endeavors.
  • Encouraged the FDA to recommend the collection of geographic heritage as well as genetic ancestry, as these data better correlate with population-level differences in relevant indicators like pharmacodynamics and pharmacogenetics.
  • Recommended the FDA include specific guidance on whether and how such data may serve as Real World Data in support of regulatory submissions.
  • Urged the FDA to consider taking additional steps to ensure clinical trial representativeness.

April 15: We responded to the draft guidance document “Use of Data Monitoring Committees in Clinical Trials” (FDA-2001-D-2019). In our response, we:

  • Suggested several challenging real-world scenarios we believe should be contemplated in the final guidance for the benefit of stakeholders.
  • Requested clarification of ambiguous or potentially contradictory guidance within the document.
  • Sought to clarify the recommended qualifications, roles, and responsibilities of the members of Data Monitoring Committees as laid out in the guidance.


Comment Opportunities on the Near Horizon

Next on the horizon, the MRCT Center will be responding to several initiatives from the National Institutes of Health (NIH), including the NIH Office of Science Policy’s draft “NIH Intramural Research Program Policy: Promoting Equity Through Access Planning,” the “ENGAGE Working Group” public engagement model, and the draft “Public Access Policy.” The Center will also be responding to recent draft guidance from the FDA regarding ICH M14and their much-anticipated guidance on Diversity Action Plans for clinical research. We are also considering responding directly to ICH regarding their draft guideline on ICH M14, which covers the use of real-world data for safety assessments of medicines.

As always, we welcome any contributions from members of the Executive or Steering Committees regarding our public comment processes. Additionally, EC/SC members are encouraged to contact our Research Analyst, Jack Ferdman (jferdman@mgb.org), to suggest materials for public comment for our review.

Projects in Scoping

Environmental Sustainability in Clinical Trials

Project lead and contact: Lisa Koppelman

The MRCT Center is exploring the complex set of issues related to environmental sustainability in clinical trials. While clinical trials contribute only a small percentage of greenhouse gas (GHG) emissions of the overall emissions from healthcare (estimated to contribute 8-12% of overall GHG emissions), each stakeholder has a responsibility to understand one’s contribution and all must play their part in mitigation efforts. While first and foremost we must ensure that only informative and necessary trials that generate reasonable data are conducted, we are cognizant that all stakeholders, at all stages along the clinical research lifecycle, also represent opportunities for improvement.  

With that multi-stakeholder focus and preliminary scoping efforts underway, we will apply what we have learned thus far to focus on developing targeted deliverables that address several preliminary objectives over the next 6-9 months: 

  1. Enhance the visibility of environmental sustainability issues in clinical trials with the range of stakeholders by supporting existing efforts and establishing the MRCT Center as a convener and collaborator in this effort. We will accomplish this by developing various materials, including publications and/or FAQ type offerings. 
  1. Elucidate mitigation opportunities by developing a checklist of sorts that highlights such opportunities.  With select organizations calculating the carbon footprint associated with each stage of a clinical trial, we will develop mitigation opportunities that track with the elements and activities of all clinical trial stages.  
  1. Define elements necessary for a common reporting tool and compile a checklist that supports the development for such a common data reporting tool. 

How EC/SC members can get involved: 

  • The MRCT Center welcomes collaborators with expertise in and/or involvement with sustainability efforts specific to the clinical trial enterprise. 

Crisis Planning Response in Research (CPRR)

Project lead and contact: Jack Ferdman

Conducting a clinical trial under ideal circumstances presents persistent and critical challenges – from safety concerns to data integrity and privacy to participant enrollment and retention – to every stakeholder across the clinical research enterprise. Unfortunately, conditions over an enterprise the scope of global clinical research are rarely – if ever – ideal. Instead, external factors often can and do further complicate the performance of a clinical trial. Such factors may include but are certainly not limited to natural disasters (e.g., hurricane, flood), infectious disease, and acts of violence or war (collectively, “crises”). Crises of this sort may occur at clinical research sites unpredictably, but the very notion that such crises will occur at all is inevitable. In broad strokes, organizations have historically responded to crisis-borne disruptions on an ad hoc, case-by-case basis. In some cases, these ad hoc responses have accumulated into a sort of response-by-evolution plan for an organization.

The MRCT Center believes that clinical research can and should be better equipped to respond to crises. To that effect, we are pleased to announce the launch of our Crisis Planning and Response in Research (“CPRR”) project. Through it, we aim to inform the preparedness and response efforts across the full research enterprise while still permitting stakeholder organizations the agility to implement appropriate guidance whenever and however the need arises.

Objectives

  • Buttress clinical trial infrastructure to withstand crisis-borne disruptions safely and ethically
  • Prioritize safety of research staff and trial participants directly affected by crises
  • Promote agility and communication within and across stakeholder organizations
  • Ensure study integrity remains intact when crises yield system failures

How EC members can get involved:

The MRCT Center welcomes collaborators with expertise in and/or involvement with crisis planning and response efforts specific to the clinical trial enterprise. 

REcent MRCT Center WEbinars and Resources

Webinar: Accessibility 101: How to Write Alt-Text and Map Participant Journeys

Presented on: July 9, 2024


Webinar: Data Collection and Privacy: Tools and Resources for LGBTQIA+ Inclusion by Design

Presented on: June 11, 2024

The MRCT Center added two new tools to the LGBTQIA+ Inclusion by Design in Clinical Research Toolkit: the SOGI Data Collection Checklist and the SOGI Data Privacy Checklist.

During this webinar we discussed:

  • The critical role of representation in clinical research, particularly for LGBTQIA+ communities, and an overview of the foundations supporting the LGBTQIA+ Inclusion by Design in Clinical Research Toolkit.
  • Essential considerations for collecting SOGI data, covering survey and form design, appropriate language in study materials, and the protocols for collecting, storing, and sharing SOGI data.
  • Practical implementation examples and areas that require further research and guidance.

Webinar: Action and Influence: Implementing the Clinical Research Glossary and Your Critical Role in Public Review

Presented on: June 4, 2024

Learn how four organizations, Mass General Brigham (MGB) Rally, HonorHealth, the Society for Clinical Data Management (SCDM), and the CureMito Foundation, are implementing the MRCT Center’s Clinical Research Glossary and how you can participate in Public Review, a vital process to ensure the glossary is a CDISC global standard.

Download the Slides
Watch the recording


Toward a National Action Plan for Achieving Diversity in Clinical Trials

The Clinical Trials Transformation Initiative (CTTI)Milken Institute’s FasterCures, the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center), and the National Academies Forum on Drug Discovery, Development, and Translation coordinated a series of three convenings (June, September, and November 2023) to inform the publication of a National Action Plan to increase diversity in clinical trials. This national action, which includes eight domains and action steps intended to drive system-wide collective action, is now available here. 


Expanded Clinical Research Glossary

The MRCT Center released a new expanded Clinical Research Glossary on April 2, 2024. Resources, including the recording, slides, and links are available here.

Highlights:

  • The glossary presents over 160 terms in plain language, complete with definitions, associated resources, and imagery.
  • You may download and incorporate the glossary, including definitions, images, and all accompanying content, to incorporate into participant communications under our Creative Commons license. Discover more here.
  • A broad coalition of stakeholders developed the terms, and a public review process further refined them through our partnership with the Clinical Data Interchange Standards Consortium (CDISC), establishing a global standard.

Opportunities to support the Clinical Research Glossary and our Health Literacy efforts

We invite Executive Committee members and organizations to participate in our health literacy efforts in the following ways: 

  • Spring 2024 – Join the Clinical Research Glossary effort by 1) identifying ways to integrate the glossary resource into internal company systems and processes, 2) sharing case study examples of how the glossary is being used/helping at your organization, 3) offering translation assistance to support expansion to non-English speakers, 4)assisting with external dissemination and outreach especially to your patient and advocacy partners to increase public review participation, acceptance of the Clinical Research Glossary, and uptake of the definitions. 
  • Fall 2024/Winter 2025 – Consider joining a small task force to review the current content on the Health Literacy in Clinical Research website and suggest updates and improvements for a new release in 2025. 

REACH: Advancing DEI in Human Participant Research

Introducing Research Ethics Action Collaborative for HRPPs (REACH), an initiative spearheaded by the MRCT Center, AAHRPP, PRIM&R, and Mass General Brigham to curate, align, and disseminate tools to advance access to and inclusion in research—for all potential participants–tailored for Institutional Review Boards (IRBs), Human Research Protection Programs (HRPPs), and the broader community. 

Click here for the webinar recording and related resources.

opportunities for further engagement

We are seeking testimonials from Executive Committee members about the value-add of sponsorship to your organization for our marketing materials.

Benefits of EC/SC Sponsorship

  • Quote: 3-5 sentences about your experience working with the MRCT Center and with fellow Executive Committee (and/or Steering Committee) members.
  • Video: 1-2 minute recording

Thank you so much in advance!