A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder

Abstract

BackgroundThe purpose of this analysis was to characterize the placebo response in antimuscarinic drug trials for OAB, based on changes in commonly-used efficacy endpoints.MethodsPlacebo arm data for incontinence episodes, micturitions, voided volume and study characteristics were extracted from randomized placebo controlled antimuscarinic drug trials in OAB, from studies identified in a prior meta-analysis, and from a systematic review of more recently published studies. Relationships between variables were examined using linear regression, and changes in endpoints were analyzed by a meta-analysis approach. The effect of placebo arm size and magnitude of placebo response on probability of successful study outcome was analyzed using an ANOVA model.ResultsChanges in the placebo arms for all 3 endpoints were substantial and statistically significant, and highly heterogeneous. There were significant associations between baseline and change scores for some but not all of the endpoints. More recent studies tended to have more subjects than earlier studies, and there were positive associations between probability of achieving statistically significant results and size of the placebo arm. The magnitude of changes in placebo arms did not appear to influence the likelihood of the study to be statistically significant.ConclusionThis analysis confirms earlier observation that the placebo response in OAB trials is substantial and highly heterogeneous. There are multiple potential reasons for this; however, these could not be explored in this analysis of study-level data. Two approaches may be used in clinical trials to manage high placebo effect: recruitment of 1) greater numbers of patients and/or 2) more severely affected patients; however, only the former approach is associated with increased probability of successful study outcome.

Effects of voluntary dose escalation in a placebo‐controlled, flexible‐dose trial of fesoterodine in subjects with overactive bladder

“…The results of the present study also differ from the results of the pooled analysis of fixed‐dose fesoterodine studies10 in that there were fewer endpoints with statistically significant differences between subjects receiving fesoterodine and those receiving placebo in the present study, whereas fesoterodine 4 and 8 mg both produced significantly greater improvement in most endpoints versus placebo in the pooled analysis of fixed‐dose studies 10. While robust placebo effects are common in OAB trials,18, 19 due perhaps at least in part to the practice of recording voiding habits in a bladder diary, the atypically large effect among placebo non‐escalators in the present study may suggest that subjects exhibiting the strongest placebo effect were self‐selected into the non‐escalator group. This may explain the lack of difference between fesoterodine and placebo non‐escalators.…”

Age and Sex as Moderators of the Placebo Response - An Evaluation of Systematic Reviews and Meta-Analyses across Medicine

“…A higher randomization ratio (90) was noted as a design factor driving higher PR in psoriasis, and lower symptom severity at baseline (86,93) as patient-based factor driving the PR.…”

Treating Urge Incontinence in Older Women: A Cost-Effective Investment in Quality-Adjusted Life-Years (QALY)

“…Both US and European analyses have concluded that no drug is consistently more effective than another [5,7,22] and the focus here is pharmacological versus behavioral approaches, not on comparison of individual drugs. The drug treatments reviewed were extended-release tolterodine, extended-release oxybutynin, trospium, solifenacin, darifenacin, and fesoterodine; all have been studied extensively for the treatment of incontinence [13,14,[23][24][25][26][27]. Figure 1 shows the treatment pathway for FBT for illustration; the other two treatments follow the same model.…”