title: Uncertainty about effects is a key factor influencing institutional review boards' approval of clinical studies.
abstract: OBJECTIVE
  To investigate factors, which influence institutional review boards' (IRBs') decision to approve or not approve clinical studies, a nationwide vignette-based online survey of IRB members was conducted.
  
  
  METHODS
  A factorial design was used, whereby seven aspects of each hypothetical study were randomly varied in 15 phrases in each vignette to produce unique vignettes. Participants indicated the degree of study approval and described factors influencing approval decision. Qualitative responses were thematically content analyzed.
  
  
  RESULTS
  Sixteen themes were obtained from 208 participants from 42 institutions. Uncertainty, adherence, study design, and harms were frequently and intensely cited to influence study approval. Analysis of two extreme subgroups (approvers vs. nonapprovers) showed that uncertainty influenced approval decisions, odds ratios (OR) = 3.5 (95% confidence interval [CI], 1.3-9.8) and OR = 3.2 (95% CI, 1.1-8.9), respectively, based on theme frequency and theme intensity, ignoring multiple observations per person. Taking into consideration multiple observations per person, similar results were obtained for uncertainty: OR = 8.9 (95% CI, 0.93-85.4).
  
  
  CONCLUSIONS
  Perceived uncertainty about benefits and harms of a proposed intervention is a key driver in IRB members' approval of clinical trials. This, in turn, calls for improved standardization in the communications of information on benefits and harms in the research protocols considered by the IRBs.
authors.affiliation: Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, USF Health Morsani College of Medicine, University of South Florida, Tampa. Electronic address: hwao1@health.usf.edu.
authors.forename: Hesborn
authors.initials: H
authors.lastname: Wao
authors.affiliation: Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, USF Health Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mhaskar
authors.affiliation: Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, USF Health Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, USF Health Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Branko
authors.initials: B
authors.lastname: Miladinovic
authors.affiliation: Center for Survey Research, Weldon Cooper Center for Public Service, University of Virginia, Charlottesville.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guterbock
authors.affiliation: Department of Mathematics and Actuarial Science, Indiana University Northwest, Gary.
authors.forename: Iztok
authors.initials: I
authors.lastname: Hozo
authors.affiliation: Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, USF Health Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
mesh_terms: D000328:Adult; D000368:Aged; D035843:Biomedical Research / Q000941:ethics / Q000592:standards*; D003625:Data Collection; D003659:Decision Making, Organizational; D028744:Ethics Committees, Research / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D036301:Qualitative Research; D012107:Research Design / Q000592:standards*; D035501:Uncertainty
keywords: Benefit risk assessment; Clinical ethics committee; Clinical protocols; Decision-making; Empirical research; Institutional review board; Research ethics