Race, Medicine, and Political Correctness

Should “race” be a criterion for inclusion in a clinical trial — and, by extension, is it appropriate for drug labeling to mention it specifically? For instance, should a drug’s label say that only “white people” should take it? Those are complicated questions, but the simple answer is that you go where the data take you.

Clinical trials are not designed to show the effectiveness of a treatment (drug, medical device, or other intervention) in a completely random sample of people in the general population. Instead, researchers use a variety of strategies to select a subset of patients in whom the intervention will likely be easier to demonstrate. This concept is called “enrichment,” which is defined by the FDA as “the prospective use of any patient characteristic to select a study population in which detection of a drug effect (if one is in fact present) is more likely than it would be in an unselected population.”

As the FDA observes in an agency guidance document on enrichment strategies, “Some of these selection strategies are obvious (e.g., patients are enrolled only if they have the disease that the drug being studied is intended to treat), but there are many more ways in which patients are typically chosen to make detection of a treatment effect more likely.” An increasingly important approach is the use of biological indicators, or “biomarkers” — such as certain DNA sequences or the presence or absence of drug receptors — as an indicator of the likelihood that the intervention will be effective and, therefore, whether a given patient should be eligible for the clinical trial.

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Genetic markers are obviously useful for obtaining enrichment, but how about more subjective factors such as “race” or ethnicity?

Dr. Abigail Zuger, a professor of medicine at Columbia University in New York, has strong opinions about the subject: “It has been clear for decades that race has minimal relevance to the body’s inner workings. Research has repeatedly shown that the biologic variations among individuals of the same race are reliably great enough for race to retain little utility as a biologic predictor. You might as well sort people by height.”

Zuger’s disdain for sorting by height is misplaced: If you were testing a growth-promoting drug in children of short-stature, for example, you would select only subjects of less than average height for the trial. {snip}

Such uncompromising, sardonic statements appear to owe more to political correctness than to human biology — or to the actual practice of medicine. In fact, because they do sometimes reflect “the body’s inner workings” — that is, differences in physiology — diagnostic tests and therapeutic interventions targeted at certain ethnic or racial categories can be useful.

In order to screen for a number of genetic diseases that occur predominantly in Jews of Ashkenazi, or Eastern European, descent, for example, there is a group of genetic tests called the Ashkenazi Jewish Genetic Panel (AJGP). Similarly, sickle-cell anemia is found disproportionately frequently in blacks, and a hereditary enzyme deficiency that causes sensitivity to fava beans and certain drugs is found primarily in Africans and persons of “Mediterranean” descent; after exposure to quinine-like drugs, as many as 10 percent of black men develop a serious condition in which red blood cells lyse, resulting in severe anemia.

Thus, race or ethnic origin — although far less precise than molecular markers — can sometimes serve as a useful surrogate for more precisely defined genetic differences.

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But let us return to Dr. Zuger’s comments, made in the context of reviewing a book about a cardiac drug called BiDil, which was approved in the United States in 2005 specifically for black patients (although it can be prescribed off-label for anyone). Due to the lack of evidence of efficacy in early clinical trials, the drug, which is actually a combination of two proven cardiac medicines (the vasodilators hydralazine and isosorbide dinitrate), had been rejected by the FDA nine years previously for approval for patients of all races. But because analysis of the data in various subgroups revealed a suggestion of benefit to black patients, another trial was performed on 1,050 self-identified black patients with severe heart failure who had already been treated with — but had not responded to — the best available therapy.

The results were so striking — 43 percent reduction in mortality and 39 percent decrease in hospital visits among patients who received BiDil — that the study was stopped early and the drug was approved. This is an enrichment success story. Since its approval, BiDil has not been a great commercial success but it remains on the market.

Commentators have expressed a wide spectrum of views about the appropriateness of a therapy designated for one racial group, some even calling it discriminatory. Francis Collins, then director of the U.S. National Human Genome Research Institute (and now head of the National Institutes of Health) said at the time BiDil was approved that “we should move without delay from blurry and potentially misleading surrogates for drug response, such as race, to the more specific causes.”

He was correct, of course. But you go to war against illness with the data you have, not the data you wish to have. Political correctness notwithstanding, drug testing, approvals, and labeling must go wherever the evidence leads.