Introduction: Although work to date in cystic fibrosis (CF) has elucidated frequencies and characteristics of adverse events, the accuracy of attribution of relatedness to study drug by investigators has not been assessed. We aimed to determine whether there was an association of attribution by group allocation in CF clinical trials.
Methods: We conducted a secondary analysis from 4 CF trials of all persons who experienced an AE. Our primary outcome was the odds of an AE related to active study drug and predictor of interest was the treatment allocation. We constructed a multivariable generalized estimating equation model allowing for repeated measures.
Results: A total of 785 subjects (47.5% female, mean age 12 years) had 11,974 AEs, of which 430 were serious. AE attribution was greater with receipt of active study drug as compared to placebo but did not reach statistical significance (OR 1.38, 95% CI 0.98-1.82). Significantly associated factors included female sex (OR 0.58, 95% 0.39-0.87), age (OR 1.24, 95% CI 1.06-1.46) and baseline lung function (per 10%, OR 1.16, 95% CI 1.05-1.28).
Conclusion: In our large study, there was a non-significant but greater odds of AE attribution (a key element of clinical trial reporting) to active study drug based on assigned treatment to study drug or control which suggests that there is a trend in physicians to attribute blinded safety data to the active drug. Interestingly, females were less likely to have AE attribution to study drug and warrants further work in development and validation of monitoring guidelines and processes.
Keywords: Adverse event; Bias; Clinical trial; Cystic fibrosis; Female sex; Safety monitoring.
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