Baseline-dependent improvement in CF studies, plausibility of bias.

Background: It has been commonly reported that therapeutic treatments in cystic fibrosis (CF) have ceiling effects, such that their efficacy is diminished for persons with high pre-treatment health (Montgomery et al., 2012 and Newsome et al., 2019). Floor effects have also been reported where decline is of lower magnitude in those with below-average pre-treatment health (Harun et al., 2016; Konstan et al., 2012 and Szczesniak et al., 2017). When measurement error is present, the statistical literature has warned of exaggerated or spurious associations between pre-treatment measures and subsequent change (Chambless and Davis, 2003 and Yanez et al., 1998). Measurement error, equivalently described as day-to-day variation, has been described to occur in CF outcome measurements such as forced expiratory volume in 1 s taken by spirometry (FEV Methods: We conducted a simulation study to assess the potential for spurious floor or ceiling effects in studies of CF therapeutics. We considered uncontrolled or single-arm studies, and evaluated estimated association between pre-treatment FEV Results: When day-to-day variation was present in FEV Conclusion: Exaggerated ceiling effects are possible. Further studies could provide meaningful confirmation of ceiling effects in CF, perhaps reducing day-to-day variation by incorporating multiple pre- and post-treatment measurements.