Elsevier

The Journal of Pediatrics

Volume 182, March 2017, Pages 155-163.e7
The Journal of Pediatrics

Original Articles
The Placebo Response in Pediatric Abdominal Pain-Related Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis

https://doi.org/10.1016/j.jpeds.2016.12.022Get rights and content

Objective

To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders.

Study design

The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL were searched for systematic reviews and randomized placebo-controlled trials concerning children 4-18 years of age with an abdominal pain-related functional gastrointestinal disorder. The primary outcome was the pooled proportion of subjects assigned to placebo with improvement as defined by the authors. The effect of trial characteristics on the magnitude of the placebo response was investigated using univariate meta-regression analysis.

Results

Twenty-one trials were identified. The pooled proportion of subjects with improvement was 41% (95% CI, 34%-49%; 17 studies) and with no pain was 17% (95% CI, 8%-32%; 7 studies). The pooled standardized mean difference on the Faces Pain Scales compared with baseline was −0.73 (95% CI, −1.04 to −0.42; 8 studies). There was significant heterogeneity across studies with respect to both outcomes. Lower dosing frequency (P = .04), positive study (P = .03), longer duration of treatment (P < .001), and higher placebo dropout (P < .001) were associated with higher report of no pain. Response on Faces Pain Scales was greater in studies conducted in the Middle East (P = .002), in studies that did not report the randomization schedule (P = .02), and in studies with a higher percentage of females (P = .04).

Conclusions

Approximately 41% of children with abdominal pain-related functional gastrointestinal disorders improve on placebo. Several trial characteristics are correlated significantly with the proportion of patients with no pain on placebo and with the magnitude of the placebo response on Faces Pain Scales. These data could be valuable for the design of future studies.

Section snippets

Methods

The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL databases were systematically searched for studies on AP-FGIDs from inception up to April 2016. The full search strategy is provided in the Appendix (available at www.jpeds.com).

Criteria for the inclusion of studies were: (1) study was an RCT comparing the effect of placebo with any pharmacologic or nonpharmacologic treatment, (2) study population consisted of children within the age range of 4-18 years,

Results

The search yielded 1669 potentially relevant articles and abstracts. Another 2 articles and abstracts were identified by hand search. A total of 599 records were duplicates (Figure 1; available at www.jpeds.com). Of the remaining 1072 records, 1026 were excluded based on the screening of titles and abstracts. A total of 46 records were reviewed in full text, which led to the exclusion of another 25 records there were no relevant outcome measures (n = 8),23, 24, 25, 26, 27, 28, 29, 30 it was a

Discussion

The present systematic review and meta-analysis of the placebo response in children with AP-FGIDs has demonstrated a pooled improvement rate of 41% and a pooled rate of no pain of 17%. No study characteristics were associated significantly with the rate of improvement, although a trend was observed toward lower improvement rates in trials using patient-reported outcomes compared with parent- or physician-reported outcomes. Lower dosing frequency, a study with a statistically significant effect

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    The authors declare no conflicts of interest.

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    Contributed equally.

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