Heterogeneous perception of the ethical legitimacy of unbalanced randomization by institutional review board members: A clinical vignette-based survey

Abstract

Background: Institutional review boards must guarantee the ethical acceptability of a randomized controlled trial before it is conducted. However, some may regard an unbalanced randomization ratio as reflecting an absence of uncertainty between the groups being compared. The objective was to assess institutional review board members' perceptions of whether unbalanced randomization in randomized controlled trials is justified and ethically acceptable. Methods: Institutional review board members worldwide completed a survey involving clinical vignettes modeling situations classically advocated to explain the use of unbalanced randomization. Institutional review board members were asked whether unbalanced randomization was justified and ethically sound. Answers were collected by using visual analog scales. Data were analyzed by principal component analysis, and a hierarchical ascending classification was created. Verbatim answers were assessed by qualitative content analysis. Results: We analyzed responses from 148 institutional review board members. Three classes of respondents were identified: class 1 (n = 58; 39.2%), mostly skeptics who disagreed with unbalanced randomization, whatever the justification; class 2 (n = 46; 31.1%), believers who considered that unbalanced randomization was acceptable whatever the justification, except cost; and class 3 (n = 44; 29.7%), circumstantial believers for whom unbalanced randomization may be justified for methodological and safety issues but not cost or ethical issues. When institutional review board members were asked whether unbalanced randomization respected the equipoise principle, the mean quotation was low (4.5 ± 3.3 out of 10), especially for class 1 members. Conclusions: Institutional review board members perceive unbalanced randomization heterogeneously in terms of its justification and its ethical validity.