159245 Lack of planned subgroup analysis: Review of drug protocols submitted to the Food and Drug Administration

Monday, November 5, 2007: 1:30 PM

Pellavi Sharma , Office of Women's Health, Food and Drug Adminstration, Rockville, MD
Ellen Pinnow , Office of Women's Health, Food and Drug Adminstration, Rockville, MD
Pamela Scott , Office of Women's Health, Food and Drug Adminstration, Rockville, MD
Janelle Derbis, PharmD , Office of Special Health Issues, Food and Drug Administration, Chicago, IL
Theresa Toigo , Office of Special Health Issues, Food and Drug Administration, Washington DC, DC
Kathleen Uhl , Office of Women's Health, Food and Drug Adminstration, Rockville, MD
  
The Food and Drug Administration (FDA) has advocated for and later required the inclusion of women in clinical trials. It is known that drug metabolism and side effects may differ based on sex. Inclusion of women allows for the evaluation of sex differences related to the safety and efficacy of drugs. The FDA's Office of Women's Health (OWH) is tasked with monitoring the inclusion of women in clinical trials. OWH evaluated the presence of planned sub-group analyses in drug protocols submitted in Investigational New Drug Applications (IND) to the Center for Drug Evaluation and Research at the FDA.

A query of an existing Office of Special Health Issues (OSHI) database identified 655 protocols submitted to the FDA between January 1, 2002 and April 30, 2002. Protocols for non-sex specific diseases which allowed enrollment of both men and women were selected. Only 219 protocols of late phase clinical trials were examined. These include 6 trials at phase 2/3, 185 trials at phase three and 28 phase four trials. Early phases of clinical trials were not analyzed due to the anticipated small sample sizes. Excluded were 231 phase one trials, 15 phase 1/2 trials and 190 phase two trials. The analytical plans in the protocols were evaluated for the presence of planned subgroup analyses, which include sex and race/ethnic group analyses, age, medical history, and study site.

Out of 219 protocols, 48 (21.9%) reported at least one planned sub-group analysis. Twenty (9.1%) planned sex analysis, nine (4.1%) planned a race or ethnic group analysis and 17 (7.8%) planned an age analysis. Eighteen (8.2%) protocols planned to do an analysis comparing study sites.

The Institute of Medicine and the FDA have recognized and supported the inclusion of women in clinical trials and the need for subgroup analyses including sex analysis. The importance of sub-group analyses cannot be understated and various acceptable methodologies for conducting such analyses are available. Previous research has demonstrated that sub-group analyses are more accurate and occur more often when identified a priori. A review of drug protocols submitted to the FDA revealed that a priori sub-group analyses were mentioned in 21.9% of protocols and a priori sex analyses in 9.1%. The lack of reporting sub-group analyses may reflect the exploratory nature of such statistical analyses, but does not necessarily indicate that these data will not be submitted to FDA.

Learning Objectives:
By the end of the session, the participant will be able to: 1)Understand the need for sub group analyses. 2)Understand the need to analyze sex differences. 3)Describe the importance of identifying subgroup analysis a priori.

Keywords: Gender, Data Collection

Presenting author's disclosure statement:

Any relevant financial relationships? No
Any institutionally-contracted trials related to this submission?

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.

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