NEW YORK (Reuters Health) – In trials of antimuscarinic agents for overactive bladder, the placebo responses tend to be large, statistically significant, and heterogeneous, according to a meta-analysis of randomized, double-blinded, placebo-controlled trials.

“The substantial placebo response has been noted in treatment trials for other urological disorders, with both drug and non-drug interventions, and may reflect nonspecific effects related to use of a diary, behavioral training, etc., and/or to the use of subjective endpoints,” Dr. Paul Glue and associates report in the July 22 issue of BMD Medical Research Methodology.

“Therefore,” they add, “in essence, the placebo effect seen in these trials is ascribable to all non-drug aspects of the trial, in addition to treatment with placebo.”

Dr. Glue, from the Dunedin School of Medicine in New Zealand, and associates in the US identified 36 trials that met eligibility criteria: double-blind, randomized, placebo-controlled trials that reported the total number of patients assigned to placebo and at least one of three endpoints (number of daily incontinence episodes, number of micturitions per day, and/or volume voided per micturition).

The most commonly published trials involved tolterodine, oxybutynin, propiverine, and solifenacin. Median study duration was 12 weeks. The mean number of patients in the placebo arms was 163 (range 13-508), and mean age was 58.9 years.

For the endpoint of incontinence episodes/day, evaluated in 17 trials, the baseline mean number was 3.15, which declined by 1.16 episodes by the end of the trial.

For the 18 trials that evaluated mean micturitions/day, the number declined from a baseline of 11.8 episodes by 1.4 episodes.

Fifteen trials analyzed mean voided volume, which was 163 mL at baseline and increased by 12.5 mL.

The authors note that the larger placebo arm increased the likelihood of achieving statistically significant results.

“In a meta-analysis of placebo responses across different disorders, drug trials in urogenital disorders had the highest placebo response,” Dr. Glue’s team reports.

They offer a number of suggestions to reduce heterogeneity in such trials, including recruitment of greater numbers of subjects, validation of more objective endpoints, characterization of more drug-responsive subpopulations of patients, and analysis of different study designs.

Reference:
BMC Med Res Methodol 2990:9:55.