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

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.

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.

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).

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