Placebo-arm response rates for pain outcomes in chronic pancreatitis: a systematic review and meta-analysis of randomized controlled trials
4 affiliations
- 1Internal Medicine, AdventHealth Orlando, Orlando, FL, United States
- 2Kansas City University College of Medicine, Kansas City, MO, United States
- 3Gastroenterology and Hepatology, AdventHealth Orlando, Orlando, FL, United States
- 4Pancreas Center, AdventHealth Orlando, Orlando, FL, United States
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.
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BibTeX
@article{alsaleh2026placeboarm,
title = {{Placebo-arm response rates for pain outcomes in chronic pancreatitis: a systematic review and meta-analysis of randomized controlled trials}},
author = {Tareq Alsaleh and Prachi Mann and Aleena Majeed and Syed Hasaan Rahman and John George},
journal = {Frontiers in Physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1954055},
url = {https://doi.org/10.3389/fphys.2026.1954055},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Placebo-arm response rates for pain outcomes in chronic pancreatitis: a systematic review and meta-analysis of randomized controlled trials
AU - Tareq Alsaleh
AU - Prachi Mann
AU - Aleena Majeed
AU - Syed Hasaan Rahman
AU - John George
PY - 2026
DA - 2026/10/22
JO - Frontiers in Physiology
DO - 10.3389/fphys.2026.1954055
UR - https://doi.org/10.3389/fphys.2026.1954055
AB - 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.
SN - 1664-042X
ER -