NEWS

FDA Guidelines on Race and Ethnicity: Obstacle or Remedy?

James Schultz

In an effort to increase the efficacy of drug treatments and reduce potential unintended drug interactions among different racial and ethnic groups, the U.S. Food and Drug Administration has issued new guidelines calling for establishment of more detailed race and ethnicity categories in the collection of effectiveness and safety data during clinical trials of promising pharmaceuticals that the agency regulates.

Current FDA regulations require drug sponsors to present an analysis of data according to age, gender, and race. But the agency cited an increasing body of evidence that points to substantial differences in response to medications among racially and ethnically distinct subgroups of the U.S. population.

In its draft guidance, the FDA conceded that such dissimilarities may be attributable to a combination of genetics and environmental influences such as diet, exposure to pollutants or toxins, and socioeconomic status. Nevertheless, the agency stated that it hopes to strengthen reporting criteria, citing research that indicates Caucasians are more likely than people of Asian and African ancestry to have abnormally low levels of a metabolic enzyme known as CYP2D6, which is found in a range of therapeutic agents, including antidepressants, antipsychotics, and beta blockers.

Drug Responses

Other studies, the FDA reported, have shown that blacks respond poorly to several classes of antihypertensive agents, such as certain kinds of beta blockers and angiotensin converting enzyme (ACE) inhibitors. In addition, clinical trials have demonstrated lower response to interferon-alpha used in the treatment of hepatitis C among blacks when compared with other racial groups. The agency also notes that differences in skin structure and physiology appear to affect response to dermatologic and topically applied products for all races.

Category Standardization

During the past two decades, the federal government has attempted to standardize collection of race and ethnicity data in programs under federal purview. In 1997, the U.S. Department of Health and Human Services (HHS) issued a statement entitled Policy Statement on Inclusion of Race and Ethnicity in DHHS Data Collection Activities, adopting the revised categories developed by the Office of Management and Budget (OMB) for including race and ethnicity in HHS-funded and -sponsored data collection and reporting systems.

Although the FDA has long requested general race and ethnicity data on subjects in certain clinical trials, the agency has not made explicit recommendations on the categories to use when collecting and reporting that data.

Now, in its latest guidance, the FDA is suggesting that the OMB categories be systematically implemented. When ethnicity alone is considered, the agency is recommending the "minimum choices" of "Hispanic or Latino," or "Not Hispanic or Latino." When race and ethnicity information is collected separately, the FDA suggests that racial categories include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White.

But critics have long been warning that attempts at racial or ethnic categorization, however well intentioned, were fated to fall short. The authors of a 1997 Institute of Medicine report, Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations pointed out that increasing immigration and rapid rises in interracial marriages were mixing the genetic waters in North America as never before. "Racial categories that are currently in use may include people from widely different geographical locations and sociocultural backgrounds that have great genetic diversity," wrote the authors. "Thus, grouping people along racial and ethnic lines to study functional differences in their drug-metabolizing capacity or to interpret results of research and clinical trials relating to various drugs has proven to be complex and challenging."

Categorize too broadly, said Harold Freeman, M.D., director of the National Cancer Institute’s Center to Reduce Cancer Health Disparities, and you may inadvertently create therapeutic obstacles too large to surmount. Although race and ethnicity do affect behavior, and hence can impede health care delivery and outcomes, by themselves the categorizations are too broad to have definitive medical meaning. As a biological category, Freeman pointed out, race doesn’t exist, either from the point of view of a population geneticist or a cartographer of the human genome.

"You’re taking socially determined categories and applying them to biological science," he said. "There’s a danger in excluding people. The question in biological science has to be how we focus on real populations, so that our interventions will have an effect."

Exceptions

Despite recent findings, in clinical settings there are also known exceptions to assumed reactions to medications. Freeman said that cardiologists have privately told him that many of their African-American patients respond successfully to ACE inhibitors, despite some evidence to the contrary. Practitioners will not withhold or reduce medication amounts on the basis of race alone, nor should they, Freeman asserted.

"Who is Tiger Woods, for example?" Freeman said, referring to the professional golfer’s multiethnic heritage. "Race is not an absolute. When you put people in a broad category for medical purposes there’s a lot of room for error."

Otis Brawley, M.D., professor of oncology and epidemiology at the Winship Cancer Institute at Emory University, Atlanta, acknowledged that there are pronounced genetic differences among populations in response to medications, but he noted that race is a poor surrogate for more complete understanding of how individuals respond to treatment.

As evidence, Brawley points to whites in Spain, Greece, and the Middle East who have the characteristic mutation that causes sickle cell anemia, popularly thought to be a "black" disease. In the end, he said, discerning the precise area of geographic origin is a far more accurate means of assessing genetic therapeutic response. The FDA is floating a smokescreen to cover the real issue, Brawley argued, which is equitable access to health care.

"I’m incredibly concerned. In some ways [the suggested guidelines are] antiscientific," Brawley said. "Race is not, nor should it be, a biological categorization. I understand the goal is not to harm people. But this is medical racial profiling. It helps perpetuate disparities but does nothing to address them. We obsess about the small or nonexistent genetic differences between the races and ignore the real reason for health care disparities: differences in quality of delivery."

Steven Galson, M.D., director of the FDA’s Center for Drug Evaluation and Research, countered that race and ethnic categories are used throughout the government. "There’s nothing new here," Galson said. "We don’t think this [guidance] will give us massive new amounts of information down to the genetic fingerprint level. It won’t change the way we approve drugs or provide dramatic new insight into drug efficacy and safety. [But] this will facilitate uncovering more of those cases where there are ethnic or racial differences. It might be helpful in some cases."

The guidelines are in draft form only, and the agency emphasized that the guidelines should be understood only as a recommendation, until and unless specific regulatory or statutory requirements are developed. The draft guidance does not address increasing the number of current studies in which certain groups are exposed to a specific medication, nor does it advocate any increase in the total number of participants involved in clinical trials.


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