Sex and Gender Subgroup Analyses of Randomized Trials: The Need to Proceed With Caution

Aulakh, Amandev K.; Anand, Sonia S.

doi:10.1016/j.whi.2007.04.002

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Volume 17, Issue 6 , Pages 342-350, November 2007

Sex and Gender Subgroup Analyses of Randomized Trials:

The Need to Proceed With Caution

Amandev K. Aulakh, BHSc
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
- Amandev Aulakh is a Masters Student in Health Research Methodology at McMaster University and is supported by a CIHR-HSFO CARING Network Masters Studentship.
Sonia S. Anand, MD, PhD, FRCPc
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Doctor Sonia Anand is a recipient of a Canadian Institutes of Health Research (CIHR) Clinician-Scientist Award (Phase 2) and is the Eli Lilly May Cohen Chair in Women’s Health at McMaster University.
- Correspondence to: Dr. Sonia Anand, The CARING Network, MDCL Rm. 3500, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. Phone: 905-527-4322, ext 44557; fax: 905-577-1490.

Received 20 July 2006; accepted 16 April 2007. published online 16 October 2007.

Introduction and background

Subgroup analyses by sex or gender can raise potential differences in response to medical interventions which require further investigation. However, sex/gender-based SGA have the potential to be misleading if their results are overinterpreted and may incorrectly influence medical management.

Objectives

We sought to assess the frequency of subgroup analysis (SGA) by sex/gender in randomized controlled trials (RCTs) of cardiovascular disease (CVD), to determine the comprehensiveness of these analyses, and to determine the proportion of SGA considered proper using predefined criteria.

Methods

Using the terms “cardiovascular disease,” “randomized controlled trial,” and “sex” or “gender,” the EMBASE, Medline and Cochrane Central Register of Controlled Trials databases were searched from January 1990 to April 2006. Studies were excluded if they were review articles, not randomized controlled trials, or included 1 sex only. This search yielded 169 eligible studies. All RCTs including a sex/gender SGA were scored for comprehensiveness using predefined criteria and assessed for completing a proper SGA. Two individuals performed the data extraction with Cohen’s kappa coefficient of 0.81 for interrater agreement.

Results

The number of studies performing a SGA by sex/gender increased from 1990 to 2005. Of the 169 studies, 53% (n = 89) performed a sex/gender SGA. Of those with a SGA, 35% (n = 31) completed a proper SGA and 38% (n = 34) received comprehensive scores of ≥3 (out of 4).

Conclusions

Performing sex/gender SGA is common in CVD RCTs. However, many SGAs are not properly conducted and their results should be viewed cautiously. Investigators should follow guidelines to ensure the proper conduct of SGA to prevent misleading conclusions from becoming adopted by clinicians.