News Release

Society report encourages preliminary sex analysis of clinical trial data

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Society for Women's Health Research

Washington, DC – Noting that women should be appropriately included in clinical research, the Society for Women's Health Research today issued a report that encourages the application of sex analysis early in the clinical research process to more accurately gauge sex-based differences.

Published online Tuesday by Medscape, the report, Understanding the Biology of Sex and Gender Differences: Using Subgroup Analysis and Statistical Design to Detect Sex Differences in Clinical Trials, addresses the importance of statistical design and subgroup analysis to ensure that drug trials are able to detect any sex differences in response to an investigational drug or device.

"This report addresses the importance of detecting sex differences in early-phase clinical trials and translating those findings into appropriate dosing regimens. We've made great strides to include women in clinical trials, but now we must focus on the design of these trials to most accurately and efficiently detect differences in men and women," said Sherry A. Marts, PhD, scientific director of the Society for Women's Health Research and co-author of the survey.

The Society for Women's Health Research report focuses on a July 2001 Scientific Advisory Meeting and workshop that featured a variety of clinical researchers who spoke on methodologies available for appropriate sex analysis of clinical trial data.

Highlighting the importance of timely subgroup analysis for obtaining accurate and cost-effective results, Carl Peck, MD, Professor of Pharmacology and Medicine at the Center for Drug Development Science at Georgetown University, spoke on pharmocokinetic and pharmacodynamic analysis and the importance of conducting such analyses within the first phase of a clinical trial.

Peck referred to the lipid protease inhibitor tirilazad as an example of how untimely subgroup analysis can lead to a drug's failure in the approval process. In animal models of stroke, tirilazad was highly effective in reducing damage in the brain from infarcts. After four phase two trials of tirilazad in Europe and the United States failed to show positive results, Peck performed a retrospective review of the data.

He found that the most likely explanation for the lack of effectiveness was that the study subjects were underdosed. A careful study of the pharmacokinetic and pharmacology data revealed that the drug clearance rate in women was 149 percent greater than the clearance in men. In other words, he pointed out, the same dose of drug would result in two thirds less drug in the blood and brain of women compared with men.

Peck indicated that because men and women in the trials were given the same dose of the drug, women received subadequate doses and the drug appeared to be ineffective. If women were given a higher dose, it is possible that the drug could have been shown to be effective, and because the data from the first and second phases of the trials were not analyzed by sex, a potentially efficacious drug was lost.

"What we are asking is that researchers take seriously the possibility that there might be sex differences in whatever they are measuring. We want them to design studies to reveal those differences, and to report what they find," Dr. Marts said.

According to the report, In May 2000, a General Accounting Office (GAO) report revealed that although women are now participating in clinical trials in numbers proportionate to their numbers in the general population, data collected in this research are not routinely being analyzed by sex. Without such analysis, clinically relevant information about potentially lifesaving treatments could be lost.

"It seems clear that these analyses will serve to promote safer and more effective drugs for both men and women. As the field of clinical research advances, clinical trial design and statistical analysis will become even more important as we move into an era of personalized medicine," said Phyllis Greenberger, M.S.W., president and CEO of the Society for Women's Health Research.

GlaxoSmithKline, the Lilly Centre for Women's Health, Eli Lilly and Company, and the National Institute of Environmental Health Sciences sponsored the Scientific Advisory Meeting and workshop.

Visit Medscape online to access the Society for Women's Health Research report: http://www.medscape.com/viewarticle/455924.

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The Society for Women's Health Research is the nation's only not-for-profit organization whose sole mission is to improve the health of women through research. Founded in 1990, the Society brought to national attention the need for the appropriate inclusion of women in major medical research studies and the resulting need for more information about conditions affecting women. The Society advocates increased funding for research on women's health, encourages the study of sex differences that may affect the prevention, diagnosis and treatment of disease, and promotes the inclusion of women in medical research studies. Visit the Society's Web site at www.womens-health.org for more information.


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