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Patrick Y. Lee, BA; Karen P. Alexander, MD; Bradley G. Hammill, MA; Sara K. Pasquali, BS; Eric D. Peterson, MD,MPH

JAMA. 2001;286:708-713.

Context  Elderly persons and women were underrepresented in randomized controlled trials (RCTs) prior to 1990. Since then, efforts have been made to correct these biases, but their effect is unclear.

Objective  To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence.

Data Sources  The MEDLINE and Cochrane databases were searched for English-language articles from January 1966 to March 2000 regarding myocardial infarction, unstable angina, or acute coronary syndromes. Additional data sources included meta-analyses, review articles, and cardiology textbooks. Estimates of community-based myocardial infarction rates came from the National Registry of Myocardial Infarction and the Worcester Heart Study.

Study Selection  Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer, those without clinical end points, papers published in a language other than English, and unpublished manuscripts were excluded. Of 7645 studies identified, 593 RCTs were selected for review.

Data Extraction  The RCTs were abstracted by 2 of the authors for year of publication, source of support (ie, funding), pharmacotherapy, study phase, number of study sites, trial location, number of patients, mean age of the study population, and any age exclusion criteria for enrollment.

Data Synthesis  The number of published RCTs with explicit age exclusions has declined from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients aged 75 years or older increased from 2% for studies published during 1966-1990 to 9% during 1991-2000, but remains well below their representation among all patients with myocardial infarction (37%) in the United States. Enrollment of women has risen from 20% for studies published between 1966-1990 to 25% during 1991-2000, but remains well below their proportion of all patients with myocardial infarction (43%) in the United States.

Conclusions  Attempts at making cardiovascular RCTs more inclusive appear to have had limited success; thus, women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence. Because safety and efficacy can vary as a function of sex and age, these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.

Author Affiliations: Outcomes Research and Assessment Group and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.

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