This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (9)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Statistics and Research Methods  • Humanities  • Medicine and the Media  • Journalology/ Peer Review/ Authorship  • Review  • Randomized Controlled Trial  • Alert me on articles by topic

A Systematic Sampling Review

Harriette G. C. Van Spall, MD; Andrew Toren, MD; Alex Kiss, PhD; Robert A. Fowler, MD, MS

JAMA. 2007;297:1233-1240.

Context  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.

Objective  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.

Data Sources and Study Selection  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.

Data Extraction  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.

Data Synthesis  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.

Conclusions  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.

Author Affiliations: Department of Medicine (Drs Van Spall and Fowler), Division of Cardiology (Dr Van Spall), Interdepartmental Division of Critical Care Medicine (Dr Fowler), Sunnybrook Health Sciences Centre (Drs Kiss and Fowler), University of Toronto, Toronto, Ontario; and Department of Ophthalmology, University of Ottawa, Ottawa, Ontario (Dr Toren).

RELATED LETTERS

Eligibility Criteria of Randomized Controlled Trials
Giorgio Costantino, Elisa Ceriani, Anna Maria Rusconi, and Nicola Montano
JAMA. 2007;298(1):39.
EXTRACT | FULL TEXT  

Eligibility Criteria of Randomized Controlled Trials—Reply
Robert A. Fowler and Harriette G. C. Van Spall
JAMA. 2007;298(1):39-40.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial
Aubin et al.
Thorax 2008;63:717-724.
ABSTRACT | FULL TEXT  

Update on pharmacologic and nonpharmacologic therapies for smoking cessation
Schmelzle et al.
cfp 2008;54:994-999.
ABSTRACT | FULL TEXT  

Eligibility Criteria of Randomized Controlled Trials
Costantino et al.
JAMA 2007;298:39-39.
FULL TEXT