Handen 2005.

Study characteristics
Methods	Cross‐over trial of secretin versus placebo
Participants	Inclusion criteria: children with autism free of gastrointestinal disorders Exclusion criteria: included current or lifetime diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, and psychotic disorder, NOS uncontrolled epilepsy or taking ≥ 2 anticonvulsants use of other psychotropic medications unless the medications have been stable for at least 1 month prior to the start of the trial and remained stable throughout the trial any other significant medical conditions, gastrointestinal symptoms including diarrhoea and constipation, or pancreatitis Location/setting: research centre at the Children’s Hospital of Pittsburgh Sample size: 8 in total (cross‐over) Number of withdrawals/dropouts: none reported Gender: 7 male, 1 female Mean age: 7 years, 6 months IQ: "IQs ranged from moderate mental retardation [intellectual disability] to gifted (with two subjects functioning within the moderate range of mental retardation, three within the mild range, one with borderline intellectual functioning, one with average abilities and one functioning within the gifted range)". Baseline ABC‐I or other BoC: ABC‐I 11.4 Concurrent medications: not reported History of previous medications: not reported
Interventions	Intervention (porcine secretin): 2 infusions of porcine secretin at a dose of 2 IU/kg at the start of the secretin phase and 2 months later Comparator (placebo): single 2 IU/kg dose of placebo
Outcomes	Primary outcomes: irritability, measured using the ABC‐I (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessment: baseline, 1 month and 2 months post‐infusion
Notes	Study start date: not reported Study end date: not reported Source of funding: "this research was supported by a small grant to the authors from the General Clinical Research Center at Children's Hospital of Pittsburgh" Conflicts of interest: none disclosed Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Allocated by hospital pharmacist
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not described
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not clear how many participants were originally randomised to the study
Selective reporting (reporting bias)	Unclear risk	The primary outcomes mentioned at the start of the paper are the ABC (and 5 subscales), the CGI, the Dosage Record and Treatment Emergent Symptom Scale (DOTES), and the Gilliam Autism Rating Scale (GARS). Adverse events were not recorded, although the other 3 scales were recorded in full.
Other bias	Unclear risk	Cross‐over study and all participants appear to have completed both phases of the study