Estimating the Placebo Effect on Patient-Reported Outcomes in Sham-controlled Device Trials: Insights from REDUCE...

Area of Science:

• Cardiology
• Clinical Trials
• Patient-Reported Outcomes

Background:

• Patient-reported outcomes (PROs) are increasingly vital endpoints in clinical trials.
• The magnitude of placebo effects versus other trial participation benefits in control arms remains unclear.
• This study quantifies placebo effects on heart failure symptoms using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS).

Purpose of the Study:

• To estimate the magnitude of the placebo effect in heart failure clinical trials.
• To assess changes in KCCQ-OS scores after patient unblinding.
• To determine the reliability of PROs as clinical trial outcomes.

Main Methods:

• Utilized data from the REDUCE LAP-HF II trial, randomizing patients to an atrial shunt or sham procedure.
• Collected KCCQ-OS scores at baseline, 2 years (post-unblinding), and 3 years.
• Calculated changes in KCCQ-OS for sham-treated patients to estimate placebo effect and its loss, and for shunt-treated patients to estimate treatment benefit.

Main Results:

• Among 421 participants, sham-treated patients (N=182) showed a +9.3±22.4 point KCCQ-OS improvement at 2 years, with a -1.7±18.2 point decrement after unblinding.
• Shunt-treated patients (N=239) had a +12.7±22.8 point KCCQ-OS improvement at 2 years, with a +1.9±18.2 point increase after unblinding.
• The estimated mean placebo effect on KCCQ-OS was small (≤2 points).

Conclusions:

• The estimated placebo effect and its loss on KCCQ-OS in a sham-controlled device trial were minimal.
• These findings increase confidence in using PROs as reliable clinical trial outcomes.
• The study highlights the modest impact of placebo effects on patient-reported heart failure symptoms.