Bias in Treatment Assignment in Controlled Clinical Trials

TLDR

Controlled trials of acute myocardial infarction provide a setting to examine how bias in treatment assignment may affect outcomes. The authors classified 145 studies into blinded randomization, potentially unblinded randomization, and nonrandom control selection groups. Maldistribution of prognostic variables occurred in 14 % of blinded, 26.7 % of unblinded, and 58.1 % of nonrandomized studies, while significant case‑fatality differences were seen in 8.8 %, 24.4 %, and 58.1 % respectively, underscoring the need to conceal treatment allocation from recruiters. Published in N Engl J Med 1983; 309:1358–61.

Abstract

Abstract Controlled clinical trials of the treatment of acute myocardial infarction offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment. A group of 145 papers was divided into those in which the randomization process was blinded (57 papers), those in which it may have been unblinded (45 papers), and those in which the controls were selected by a nonrandom process (43 papers). At least one prognostic variable was maldistributed (P<0.05) in 14.0 per cent of the blinded-randomization studies, in 26.7 per cent of the unblinded-randomization studies, and in 58.1 per cent of the nonrandomized studies. Differences in case-fatality rates between treatment and control groups (P<0.05) were found in 8.8 per cent of the blinded-randomization studies, 24.4 per cent of the unblinded-randomization studies, and 58.1 per cent of the nonrandomized studies. These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration. (N Engl J Med 1983; 309:1358–61.)