Genetic Studies Must Include Minorities, Expert Panel Says

The final report from last year’s APA-sponsored conference, “Genetics, Response, and Cognitive Enhancers: Implications for Alzheimer’s Disease” (GRACE) (Psychiatric News, January 5, 2001) urges researchers trying to solve the disease’s many riddles to include more ethnic minority subjects.

APA convened the GRACE conference, held at the National Institutes of Health campus in December 2000, in collaboration with the National Institute on Aging, the National Institute of Mental Health, the Alzheimer’s Association, and the American Association for Geriatric Psychiatry. The conference brought together experts in geriatrics, genetics, psychiatry, and pharmacology.

The GRACE expert-panel’s report, released in December 2001, notes that some studies already hint that genetic factors may affect which populations are more likely to get Alzheimer’s disease, how quickly their disease will progress, and what drug therapies might be the most beneficial to patients of particular ethnic backgrounds.

“It is of critical importance to understand the role of ethnicity and genetic markers in treatment response,” the report emphasizes, “but these data are not yet available, in part due to the poor representation of ethnic and cultural minorities in most treatment trials.”

Dearth of Ethnic Data

In fact, the report notes, diverse ethnic groups have been poorly represented in clinical drug trials, not only in the United States, but worldwide. Only about 10 percent of participants in the National Institute on Aging’s Alzheimer’s Disease Cooperative Study clinical trials were non-Caucasian, according to the report. In a review compiled by pharmaceutical company participants in the GRACE conference, of industry-sponsored clinical trials of psychotropic medications, the companies found that less than 5 percent of participants were non-Caucasian. Comparatively speaking, according to the GRACE report, about 16 percent of the general population over the age of 65 are non-Caucasians.

In order to correct the dearth of ethnic data, “it should be a major priority to increase recruitment and retention of diverse populations in clinical trials and to find ways to increase collection of material for genetic studies in populations participating in these trials,” the report concludes.

“Genetics do play a role in the likelihood of developing—or being protected from—Alzheimer’s disease, and perhaps, in responding to therapy,” said GRACE conference chair, Jacobo Mintzer, M.D., professor of psychiatry at the Medical University of South Carolina and a consultant to APA’s Committee on Ethnic Minority Elderly.

Mintzer believes that more information is needed to identify genetic factors that play a role in Alzheimer’s disease, particularly factors that are linked to a shared common ancestry or ethnicity.

“An understanding of the role of genetics in Alzheimer’s disease is crucial to enable researchers to develop more effective therapies for this debilitating disease,” Mintzer said in a statement issued with the report.

Ethnicity’s Influences

Because Alzheimer’s disease does not appear to spare individuals preferentially based on ethnicity or gender, the report concludes that a portrait of Alzheimer’s patients should “reflect the diversity of our communities with regard to both demographic variables and socioeconomic and income levels.”

The role that genetic factors play could be a key in not only diagnosing, but treating the disease, the report states. “Overall genetic factors may affect the prevalence, progression, and presentation of Alzheimer’s disease, as well as the response to pharmacologic treatments,” the report concludes.

The expert panel also agreed that, scientifically, inclusion of non-Caucasian populations is vital to determine generalizability of any identified gene associations, as well as to assess efficacy of markers for pharmacogenomic trials and to increase understanding of gene-environment interactions.

The panel also noted, however, that certain obstacles exist to recruiting minority patients into clinical trials. Some researchers’ lack of awareness of differing social and cultural orientations can hinder ethnic-minority participation, as can study requirements that may be inappropriate for a particular ethnic or cultural group. For example, a requirement that a spousal caregiver be present in the home could exclude many minority patients, since they are more apt to be cared for by an extended family rather than a spouse.

Some clinical sites, the panel noted, have successfully recruited ethnic minorities into clinical trials by developing a marketing-based approach to recruitment, including the use of focus groups with both potential and current research subjects.

The panel offers four conclusions in its final report:

• The identification of genes responsible for the development of Alzheimer’s may allow scientists to alter the progression of, and possibly cure, the disease. Those genetic data have important implications for trial design, enrollment, analysis, and generalizability of results.

• The genetic variability among patients and among ethnic groups in the metabolism of currently available and emerging cognitive-enhancing medications requires further investigation. Genetic-based, ethnicity-minority differences may exist that affect safety of a drug.

• It is of critical importance to understand the role of ethnicity and genetic markers in treatment response.

• It should be a major priority to increase not only recruitment and retention of diverse populations in clinical trials, but also to find ways to increase collection of material for studies in populations participating in clinical trials.

The GRACE Conference Expert Panel Summary may be obtained from Amy Levey at APA by phone at (202) 682-6119 or e-mail at [email protected]. ▪