Comments Submitted: Cancer Clinical Trial Eligibility Criteria: Performance Status

Public Comment

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We responded to a series of three FDA draft guidance documents addressing eligibility criteria for U.S.-based cancer clinical trials.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Performance Status Score  (first developed in 1948) and ECOG Performance Status Scale (first developed in 1960), are outdated and highly subjective constructs.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.

Public Comments submitted: “Declaration of Helsinki Public Comment Period Two”

Public Comments

Comments provided on: June 24, 2024

Comments provided to: World Medical Association

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.

Public Comments submitted: “Cancer Clinical Trial Eligibility Criteria: Laboratory Values”

Public Comments

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.

Public Comments submitted: “Cancer Clinical Trial Eligibility Criteria: Washout Periods and Concomitant Medications”

Public Comments

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.

Public Comments submitted: “Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products”

Public Comments

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.

Public Comments submitted: “FDA-NIH Terminology for Clinical Research”

Public Comments

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.