Placebo-arm response rates for pain outcomes in chronic pancreatitis: a systematic review and meta-analysis of randomized controlled trials

Background Improvement in the placebo arm can influence chronic pancreatitis (CP) pain trials, yet contemporary estimates of placebo-arm response are limited. We aimed to quantify placebo-arm pain response rates in medical placebo-controlled randomized controlled trials (RCTs) of CP-related abdominal pain. Methods PubMed, Web of Science, Embase, and Scopus were searched from inception to October 2025 for placebo-controlled RCTs reporting pain response among placebo-treated patients with CP. Crossover trials, procedural or device-based sham-controlled trials, and studies without extractable placebo-arm pain-response data were excluded. The primary outcome was the pooled proportion of placebo-treated patients achieving pain response according to study-specific definitions. Random-effects meta-analysis of single proportions was performed. Subgroup analyses categorized endpoints as partial pain improvement or complete pain resolution. Risk of bias was assessed using Cochrane RoB 2. Results Seven RCTs including 321 placebo-treated patients, 320 of whom contributed pain-response data, met inclusion criteria. Follow-up ranged from 3 to 26 weeks. One study was judged low risk of bias and six had some concerns; no study was high risk. The pooled placebo-arm pain response rate was 26% (95% CI, 17%–36%), with heterogeneity (I² = 74.8%). Response rates varied with endpoint stringency, although the difference between subgroups was not statistically significant (P = 0.18): 31% (95% CI, 18%–46%; I² = 73.7%) in trials using partial pain improvement criteria and 20% (95% CI, 12%–29%; I² = 42.1%) in trials requiring complete pain resolution. Leave-one-out sensitivity analysis did not materially alter the estimate. Conclusions One-quarter of placebo-treated patients in CP RCTs experience pain response. Endpoint stringency may influence observed placebo-arm response and should be considered in sample-size estimation, outcome selection, and interpretation of CP pain trials.