title: The Placebo Response in Pediatric Abdominal Pain-Related Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis.
abstract: To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Daniël R
authors.initials: DR
authors.lastname: Hoekman
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Zeevenhooven
authors.affiliation: Medical Library, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Faridi S
authors.initials: FS
authors.lastname: van Etten-Jamaludin
authors.affiliation: Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Iuke
authors.initials: I
authors.lastname: Douwes Dekker
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Benninga
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Merit M
authors.initials: MM
authors.lastname: Tabbers
authors.affiliation: Department of Pediatrics, St. Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Arine M
authors.initials: AM
authors.lastname: Vlieger
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D010372:Pediatrics; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D010919:Placebos
keywords: determinants; improvement; magnitude