The US Food and Drug Administration’s (FDA) draft guidance on collection of race and ethnicity data in clinical trials is on target as the nation becomes more diverse, but it may not go far enough, according to stakeholder comments.
Comments on FDA’s new draft guidance aimed at standardizing race and ethnicity data collection in clinical trials were submitted by April 29.
The document updates and expands the breadth of an earlier guidance on the topic from 2016.
The 2024 update is based on the Office of Management and Budget (OMB) Statistical Policy Directive No. 15 (SPD 15) and is aligned with relevant sections of the Affordable Care Act and the Food and Drug Administration Safety and Innovation Act, as well as Health and Human Services (HHS) guidance.
According to the draft guidance, trial participants should self-report race and ethnicity information and be able to designate a multiracial identity. If that’s not possible, sponsors should try to get the information from a first-degree relative or other knowledgeable representative.
Several stakeholders noted important aspects of FDA’s January draft that do not match the updated SPD 15 that was issued by the OMB on 29 March, replacing a 1997 directive. FDA had noted in the draft that it would “update this guidance as appropriate if OMB revises Policy Directive 15.”
In comments to Focus, an FDA spokesperson said the agency will revise the draft guidance accordingly. “In line with FDA’s stated intent, FDA will revise and replace the “Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products” draft guidance to reflect changes pursuant to Policy Directive 15,” the spokesperson said.
For example, FDA draft guidance and the new SPD 15 differ on race and ethnicity categories and the way participants are queried.
FDA recommends that researchers collect at least two ethnicity options:
For race, the agency recommended using at least the following choices, with the option to select one or more designations:
The new SPD 15 adds Middle Eastern or North African (MENA) as a minimum reporting category for race and so should the FDA, advised the Pharmaceutical Researchers and Manufacturers Association (PhRMA) and several other commenters.
Also, FDA’s draft guidance advised a two-question format for querying trial participants about race and ethnicity:
Question 1 (to be answered first): Are you Hispanic/Latino or not Hispanic/Latino?
Question 2 (to be answered second): What is your race? More than one choice is acceptable.
In contrast, the new SPD 15 advises using a single question on race and ethnicity that is more encouraging for reporting mixed identities in stakeholders’ view. The American Medical Association (AMA) noted that the category of some other race (SOR) accounted for 15% of the US population in 2020 and advised FDA to use clear language instructing participants to select all categories that apply.
“Research conducted by the U.S. Census Bureau suggests that moving from separate questions to a combined question will decrease the proportion of respondents who remain uncategorized, or within the SOR category, from about 10 percent to 1-2 percent,” the AMA wrote.
Moderna commented that the two-question format does not generate meaningful information for clinical studies.
“The epidemiological and clinical information which can be deduced from differentiating between Hispanic/Latino or not Hispanic/Latino is very limited,” Moderna wrote “Instead, an open-ended question asking for a participant’s race and their ethnicity, with the option for multiple choices, would provide meaningful demographic information for interpretation of data emerging from clinical studies.”
The FDA in its draft guidance said that it will update its race and ethnicity guidance “as appropriate” if OMB updates Directive No. 15.
“We recommend that FDA publicly communicate in advance if it determines that any updates to the draft guidance are necessary, and note such updates should be subject to public notice and comment,” PhRMA wrote.
The AMA urged speedy revision.
Including ex-US participants
Another related issue that came up in the comments was appropriateness of the guidance in the context of international trials.
The Biotechnology Innovation Organization (BIO) advised the FDA to keep the option of a two-question format as it could be appropriate for some studies.
“It is critical that the FDA maintains a flexible approach, recognizing that implementation of these changes across global systems and processes will take time and may pose unforeseen logistical challenges such as, for instance, posed by software,” BIO wrote.
BIO also noted that in some countries, there are legal limits on the routine collection of race and ethnicity information, while in others, requirements differ from FDA guidance.
“Because this FDA guidance uses race and ethnicity categories developed in the US, this may pose challenges for sponsors with multi-regional clinical trials,” BIO wrote.
“It would be helpful for the Agency to provide clarity on how FDA plans to interpret data from global studies, such as whether it considers a Black person in the US to be the same race as a Black person from South Africa,” BIO wrote.
Cellino Biotech wrote that it supports FDA’s recommendation to supplement racial categories by geographic region but noted that there are differences in ancestry within a particular racial group.
“This is especially important for sponsors who are running clinical trials outside of the United States,” Cellino wrote.
Broadening Black categories
While FDA guidance outlined five main racial groups, it suggested that additional detailed race and ethnicity data could be collected where appropriate, including in international trials. The agency suggested racial categories could be expanded using HHS guidance and OMB standards, noting for example, seven Asian subgroups and four Hispanic/Latino subgroups.
Subgroups for Black/African American were not included in the draft. The Hepatitis B Foundation wrote that the FDA’s proposed race classification falls short when it comes to people who identify as Black.
“Grouping Blacks who are African American with Blacks who are of African origin significantly impacts the diversity of participants in clinical trials as many drug sponsors may use this as basis to only recruit African Americans into clinical trials,” the Hepatitis B Foundation wrote. “This is particularly important for hepatitis B as those from African origin and living with hepatitis B are usually impacted by certain genotypes of hepatitis B virus that are different from the genotypes that affect those living in North America.”
The Lupus Clinical Investigators Network (LuCIN), an organization of trial sites in North America, noted that with race and ethnicity being social constructs, not biological determinants, disparities in outcomes for lupus patients are often due to inequitable healthcare access.
“In addition to improving upon the racial and ethnic data collected in clinical studies and clinical trials, it is imperative to explore the inclusion of socioeconomic variables such as income, healthcare access, education, cultural/religious affiliations, and geographical location,” LuCIN wrote.
LuCIN also recommends the FDA should emphasize collection of data on genotypes and biomarkers associated with drug metabolism.
“These complementary measures not only enrich the depth of data collected but also offer insights into the underlying genetic and physiological factors that may contribute to differences in health outcomes,” LuCIN wrote.
In a similar vein, the American Society of Hematology (ASH) wrote that demographic data is most reliable when combined with genomic data.
“The Society appreciates FDA’s clarification in the guidance that race is a socio-political construct and not a biological one, and that self-reporting of race and/or ethnicity could be unreliable as such,” ASH wrote.
FDA should leverage the expertise of geneticists to inform revisions and add language on the incorporation of genomic data, ASH suggested.
“In addition, we hope the Agency considers the Society as a resource both in incorporating genomics as well as articulating the importance of collecting this information,” ASH offered.
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