Document Type
Article
Publication Title
Frontiers in Physiology
Abstract
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.
DOI
10.3389/fphys.2026.1954055
Publication Date
10-21-2026
Keywords
chronic pancreatitis, meta-analysis, pain, placebo, randomized controlled trials
ISSN
1664-042X
Recommended Citation
Alsaleh T, Mann P, Majeed A, Hasaan Rahman S, George J. Placebo-Arm Response Rates for Pain Outcomes in Chronic Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in Physiology. 2026; 17. doi: 10.3389/fphys.2026.1954055.
