Do patients with cystic fibrosis participating in clinical trials demonstrate placebo response? A meta-analysis

Abstract

Background: Patients' and families' expectation that a cure for cystic fibrosis (CF) will be found is high. In other debilitating conditions, high expectation has been shown to drive a strong placebo response (PR). Therefore, our goal was to evaluate PR on objective continuous outcomes (FEV₁, BMI) and the CF Questionnaire Revised-Respiratory Domain (CFQR-RD) monitored during randomised clinical trials (RCTs) for CF.

Methods: We conducted a meta-analysis after a systematic review of the literature carried out to identify RCTs with FEV₁, CFQR-RD and BMI as outcome measures. The standardised mean difference (SMD) was calculated to estimate the PR. A meta-regression analysis was conducted to assess other contributing factors on PR such as study design, trial duration, patient age and disease severity.

Results: Out of 289 RCTs found in the search, we identified 61 articles (published from 1987 to 2017) with respectively 59, 17 and 9 reporting FEV₁, CFQR-RD and BMI at the start and at the end of the RCTs. No significant PR was found on FEV₁ or CFQR-RD. However, a small but significant PR was found on BMI SMD, 0.09 (95% CI (0.01; 0.17); p = 0.03).

Conclusion: The PR seems higher when measuring BMI. However, it is not clear whether this improvement can be explained by a PR alone.

Keywords: Clinical trials; Cystic fibrosis; Meta-analysis; Placebo response; Randomised.