AAMC Reporter: May 2005

Anne L. Taylor, M.D. Associate Dean for Faculty Affairs, University of Minnesota Medical School

Viewpoint: "The Role of Race, Ethnicity and Geographic Ancestry in Clinical Trials"

Differences in health care outcomes amongst populations of differing race, ethnicity, or geographic ancestry are critical challenges for American medicine. Although the causes of disparities are numerous, one contributor is the absence of research to clearly identify the sources of differences in outcomes in diverse populations and to distinguish among biologic, environmental or social causes of disease differences.

Research that would contribute to a reduction in disparities requires the collection of data on health status in racial and ethnic populations, the assessment of differences in disease patterns, and the design of clinical trials with the inclusion of adequate numbers of diverse populations to probe for differences in pathophysiology (including environmental and social factors) and potential responses to treatment. Finally, where differences are observed among populations, clinical trials focused in these population groups are essential.

Despite evidence of differences in disease patterns or outcomes, clinical trials were conducted using homogenous populations with respect to age, gender and ethnicity, and the results were then generalized to all populations. Population differences with potential pathophysiologic and therapeutic implications can be obscured by this experimental design.

The recently completed African-American Heart Failure Trial and the African-American Study of Kidney Disease and Hypertension Trial are examples of studies that demonstrate the value of trials focused on racial/ethnic populations where differences in disease patterns and therapeutic responses have been observed. More than 40,000 individuals participated in another trial, the Anti-hypertensive and Lipid-Lowering to Prevent Heart Attack Trial, including 15,000 blacks and 8,100 Hispanics. This clinical trial was designed to assess racial/ethnic differences and the effect of anti-hypertensive therapy on cardiovascular outcomes.

Heart failure is a disease where there are striking population differences in almost every aspect. In addition, retrospective analyses of previous heart failure trials — in which there were, fortuitously rather than by design, sufficient numbers of African-American subjects included — suggested differences in response to pharmacotherapy. The heart failure clinical trial was designed to confirm the findings of these retrospective analyses.

When the kidney disease trial was initiated, it was known that hypertension was the leading cause of end stage renal disease in African-Americans. Hypertensive African-Americans have a four to 20 times greater risk of progression to dialysis-dependent renal disease than do whites with comparable hypertension. The data on hypertensive renal disease in African-Americans was so limited that direct measurement of kidney filtration rate and kidney biopsies was required for the kidney disease trial to establish whether the renal impairment was related to elevated blood pressure or to a previously undiagnosed, coincident, primary renal disease.

The heart attack prevention trial was designed to determine whether anti-hypertensive regimens initiated with newer anti-hypertensive agents were more effective than regimens initiated with a thiazide diuretic for the prevention of cardiovascular events in high-risk hypertensives over age 55. This trial was designed to permit evaluation of drug efficacy in African-Americans, whites and Hispanics. Significantly, there had been no previous study evaluating cardiovascular outcomes in response to blood pressure reductions with these agents in African-American or Hispanic patients.

The three clinical trials are benchmark trials focused on racial/ethnic minority populations which illustrate the importance of using differences noted in epidemiologic, observational or clinical trial databases to probe for clues to important pathophysiologic principles and variable responses to treatment which may lead to better targeted therapy. Each study has yielded important pathophysiologic data with direct positive therapeutic impact on the populations studied, as well as data that is of value to the general understanding of disease mechanisms. While it is clear that insights gained may have the greatest direct impact on the particular population segments studied, overall societal health is improved. The paucity of such studies may actually contribute to racial/ethnic healthcare disparities.

While the aforementioned studies support the concept of targeted research for particular ethnic groups, there are potent arguments for refinement of this approach. Categorization by racial, ethnic or geographic ancestry may include some genetic clustering of health risk but should not result in the neglect of socially imposed health risk factors. We clearly need more precise predictors of disease risk, expression and treatment response. These might include specific genotypes, biomarkers or metabolic phenotypes and should transcend and inform the conventional categories of race, ethnicity or geographic ancestry. Conversely, studying disease in conventionally described populations where a particular expression is more prevalent may actually facilitate characterization of specific disease mechanisms and help us to transcend the use of race, ethnicity or geographic ancestry.

It would be a missed opportunity not to study diverse populations guided by epidemiologic and clinical data, and not to design studies in which all the variables that might influence health (biologic, genetic, environmental, social) are considered. Despite the complexity of health determinants in diverse populations, these targeted trials have demonstrated how clinical trials focused in population subgroups help us to fully grasp the genus and differentia of health and disease in the human race.

Anne L. Taylor, M.D., is an AAMC Council of Deans Fellow. She has received research support from NitroMed, Inc.

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