Letter to Francis S. Collins, Director of the National Institutes of Health - Improve Racial, Ethnic Minority Representation in Clinical Trials

Letter

Dear Director Collins:

As the National Institutes of Health (NIH) conducts regular review of policy and guidelines related to grant applications, we request that existing guidance be updated to ensure eligibility criteria for clinical trials are not disproportionately excluding racial and ethnic minority groups from participation. We are encouraged by NIH's work to support research that seeks to reduce and eliminate health disparities. Specific guidance for the application and review process on recognizing when research protocols create unintentional barriers to participation will further strengthen NIH's policy and mission of inclusive enrollment of minorities in NIH-funded clinical research.

Without sufficient representation of racial and ethnic minorities in clinical trials, researchers cannot evaluate differences in the impact of treatments on these groups. Yet, racial and ethnic minority groups have been largely underrepresented in clinical trials among adults. In a systematic review of cancer treatment and prevention clinical trials that were conducted between 2001 to 2010 that reported race and ethnicity, researchers at Indiana University-Purdue University Indianapolis found more than 80 percent of clinical trial participants were Caucasian with less than 12 percent being African American, Asian, Hispanic, or Native American.

We appreciate NIH's efforts to reduce health disparities by addressing significant barriers to clinical trial participation and recognize that NIH-funded clinical trials are designed to ensure patient safety. Yet, according to a 2018 report by the American Cancer Society, eligibility criteria are often copied and pasted from previous protocols to new proposals without proper evaluation of whether it is appropriate for the current study. This may result in excluding otherwise eligible and willing participants, creating a trial population that is less representative of the population with the given disease, and making recruitment more difficult. We are concerned that eligibility criteria not clinically relevant to clinical trial outcomes may disqualify patients from enrollment who would otherwise be eligible to participate.

"Normal" organ functioning of patients is commonly used as criteria for clinical trial participation and places standard restrictions on enrollment. These criteria are meant to ensure patients are healthy enough to undergo the treatment being studied and to protect them from potential harm. However, there are known differences in the values for "normal" organ functioning across demographic groups, such as race, gender, and age. While there are formulas developed to adjust for these differences, criteria merely copied and pasted from prior protocols without consideration may cause eligible participants to be disproportionately excluded.

In a 2018 study published in the Journal of the American Medical Association, researchers examined eligibility criteria for clinical trials in prostate cancer, which disproportionately affects African American men in incidence and mortality compared with men of other racial and ethnic groups. Using a sample of prostate cancer clinical trials collected from ClinicalTrials.gov, the study found approximately 48 percent of those clinical trials used organ functioning eligibility criteria that disproportionately excluded black men and did not consider ranges of organ functioning known to be "normal" for certain groups with no additional risk to their safety. In short, black patients were excluded based on clinically insignificant reasons.

We urge that updated information on eligibility criteria be included in existing resources, ensuring ample opportunities for applicants and reviewers to recognize when proposals may cause barriers to clinical trial participation for racial and ethnic minority groups. We also ask that existing guidance include information on accounting for variations in organ functioning across population groups when determining eligibility criteria.

We thank you for your prompt attention to this important issue, and we look forward to continuing to work with you to reduce disparities in clinical trial participation.

Sincerely,