Trial methodology and patient characteristics did not influence the size of placebo effects on pain

Objective: To determine whether trial-design, patient-type, or placebo-type factors influence the size of the placebo analgesic effect in clinical trials. Study Design and Setting: Trials that measured pain outcomes in Hróbjartsson and Gøtzsche's meta-analysis were retrieved and coded for eight factors potentially predictive of placebo effect size. Random effects meta-regression was used to explore the predictive power of each factor on placebo effect size. The factors investigated aspects of trial design (nonstandardized co-analgesia, co-intervention), patients (pain type, patient group, residual pain score), and placebo (placebo type, indistinguishability, structural equivalence). The meta-analysis undertaken in the original study was also repeated to confirm the results. Results: The pooled effect of placebo was 3.2 points on a 100-point scale (95% confidence interval [CI] = 1.6-4.7). None of the selected factors influenced the size of placebo effect: the effect of all factors was close to zero, all CIs spanned 0, and P-values ranged from 0.13 to 0.90. Conclusion: This study confirms the findings of previous researchers that, at present, the evidence for large placebo analgesic effects in clinical trials is lacking. Importantly, this analysis also establishes that larger placebo effects are not associated with particular aspects of the trial methodology, patient, or placebo type.