Comments provided on: July 22, 2024
Comments provided to: National Institutes of Health (NIH) Office of Science Policy (OSP)
Description: The MRCT Center recommended that NIH OSP (1) clarify and expand on the methods to promote equitable access, (2) consider greater flexibility in the application of this policy to investigational products, and (3) require direct engagement with community stakeholders and patient advocacy groups when NIH assesses the impact of the policy.
Comments provided on: July 15, 2024
Comments provided to: Office of Science and Technology Policy
The MRCT Center submitted public comments on the White House Office of Science and Technology Policy (OSTP) Request for Information entitled, “Federal Evidence Agenda on Disability Equity,” published at 89 Fed. Reg. 46924 (May 30, 2024). The collection of reliable disability data remains a challenge to researchers, and we applaud the OSTP’s commitment to measurements of health equity that is inclusive of people with disabilities. We share OSTP’s vision for bringing disability data to the foreground and your enthusiasm for understanding where and how best to include questions on disability. In our comments, we focused on information that would be helpful for the understanding of healthcare, health disparities, and clinical research and refrained from commenting on specific survey methodology used in federal and international data collection that is beyond our area of expertise. The MRCT Center pointed the OSTP to standard practices standard practices to safeguard privacy and security, as outlined by federal policy (HIPAA, OHRP, FDA, DOD, NIH, and others) that include a management plan for secure storage and transfer of data throughout the life cycle of the project; communicating clearly with participants when, why, and how disability data will be collected and used; always providing an option for participants to opt-out of answering any or all disability data questions; and only making disability data available [to research teams] through a controlled access environment. We advocate for plain language, logical reading order, the ability to easily go back and correct answers, and the provision of reasonable accommodations during the informed consent process and in any survey/measurement instrument (whether in print, on a computer, or mobile device). Finally, we note that for any form of disability data collection, people with disabilities must first be asked to participate, and that barriers such as inappropriately restrictive screening criteria should be eliminated.
Presented on: July 9, 2024
The MRCT Center and the Research Ethics Action Collaborative for HRPPs (REACH) presented the first webinar in the Accessibility 101 series on July 9, 2024
People with disabilities are the largest minority population in the United States, yet they are often excluded from clinical trials, both as participants and as researchers. Federal regulations, such as the recently updated Section 504 of the Rehabilitation Act, prohibit discrimination based on disability. Many accommodations are easy and low or no cost. It is incumbent upon all of us to build accessibility into our everyday thinking, meetings, presentations, and planning.
This webinar featured two interactive exercises in which participants learned:
More about REACH: Research Ethics Action Collaborative for HRPPs (REACH) is 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 to learn more.
Accessibility Resources by webinar slide
Accessibility 101: Questions and Answers
Accessibility by Design (AbD) Toolkit
Submitted on: June 25, 2024
Submitted to: U.S. Food and Drug Administration; FDA-2024-D-1377
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 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.
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 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.
Artificial Intelligence (AI) refers to machine-based systems that learn from data and “learn” to perform tasks such as making predictions. Using algorithms and models, AI systems can process vast amounts of information to make recommendations or decisions that influence real or virtual environments. AI can be narrowly focused on completing a specific task but can also be purposed more generally, aiming to replicate human intelligence across multiple domains.
In 2024, the MRCT Center established a project to explore the ethical considerations when using artificial intelligence (AI) in research. AI is rapidly being deployed across all aspects of research, including as the intervention itself and in the design, planning, and analysis stages. As with all research involving human participants, research with AI should be grounded in existing ethical principles and governing regulations to protect participants.
The MRCT Center, in collaboration with WCG Clinical, convened a task force to develop resources to address ethical and regulatory challenges during the IRB review of clinical research protocols involving AI. This collaborative project includes representatives from academia, industry, AI technologists, and IRB ethicists, members, and chairs to develop resources designed to assess research protocols and evaluate the risk-to-benefit ratio of AI deployed across various aspects of clinical trials, including informed consent considerations, patient safety, and data privacy and confidentiality.
The MRCT Center is also exploring the expanding uses of data and AI in support of clinical trials, particularly the increasing use of digital twins and synthetic data to create virtual simulations of patient outcomes and evaluate the technical, ethical, and practical considerations involved.
Comments provided on: June 24, 2024
Comments provided to: U.S. Food and Drug Administration
Summary: 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.
Comments provided on: June 24, 2024
Comments provided to: U.S. Food and Drug Administration; FDA-2024-D-1376
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.
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.
Comments provided on: June 20, 2024
Comments provided to: U.S. Food and Drug Administration
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.
Comments provided on: June 18, 2024
Comments provided to: National Institutes of Health, Office of Science Policy
Summary: 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.
