Selective eligibility criteria of randomized controlled trials (RCTs) are vital to
trial feasibility and internal validity. However, the exclusion of certain patient
populations may lead to impaired generalizability of results.
To determine the nature and extent of exclusion criteria among RCTs published in major
medical journals and the contribution of exclusion criteria to the representation
of certain patient populations.
The MEDLINE database was searched for RCTs published between 1994 and 2006 in certain
general medical journals with a high impact factor. Of 4827 articles, 283 were selected
using a series technique.
Trial characteristics and the details regarding exclusions were extracted independently.
All exclusion criteria were graded independently and in duplicate as either strongly
justified, potentially justified, or poorly justified according to previously developed
and pilot-tested guidelines.
Common medical conditions formed the basis for exclusion in 81.3% of trials. Patients
were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and
38.5% in older adults). Individuals receiving commonly prescribed medications were
excluded in 54.1% of trials. Conditions related to female sex were grounds for exclusion
in 39.2% of trials. Of all exclusion criteria, only 47.2% were graded as strongly
justified in the context of the specific RCT. Exclusion criteria were not reported
in 12.0% of trials. Multivariable analyses revealed independent associations between
the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35;
95% confidence interval, 1.11-1.65; P = .003) and between the total number of exclusion
criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06-1.52;
P = .009). Industry-sponsored trials were more likely to exclude individuals due to
concomitant medication use, medical comorbidities, and age. Drug intervention trials
were more likely to exclude individuals due to concomitant medication use, medical
comorbidities, female sex, and socioeconomic status. Among such trials, justification
for exclusions related to concomitant medication use and comorbidities were more likely
to be poorly justified.
The RCTs published in major medical journals do not always clearly report exclusion
criteria. Women, children, the elderly, and those with common medical conditions are
frequently excluded from RCTs. Trials with multiple centers and those involving drug
interventions are most likely to have extensive exclusions. Such exclusions may impair
the generalizability of RCT results. These findings highlight a need for careful consideration
and transparent reporting and justification of exclusion criteria in clinical trials.