Scahill 2015.

Study characteristics
Methods	8‐week parallel trial of guanfacine versus placebo
Participants	Inclusion criteria: aged 5‐14 years DSM‐4 diagnosis of ASD, asperger's syndrome, or PDD‐NOS minimum score of 24 on the parent‐rated ABC‐hyperactivity subscale and CGI‐S score of moderate or greater Anticonvulsant medication for seizures was allowed if the dose was stable and the participant had been seizure‐free for at least 6 months IQ of 35 or mental age of ≥ 18 months Exclusion criteria: children taking a psychotropic treatment deemed ineffective were required to be withdrawn from the medication for at least 1 week for stimulants or clonidine, 2 weeks for atomoxetine and most antidepressants, and 3 weeks for fluoxetine, citalopram, and antipsychotics a significant medical condition by history, physical examination, or laboratory testing a positive pregnancy test lifetime diagnosis of psychosis or bipolar disorder or current diagnosis of major depression, obsessive‐compulsive disorder, or substance abuse Setting/ location: University of California (Los Angeles), Emory University, Massachusets General Hospital, University of Washington at Seattle, and Yale University, USA Sample size: guanfacine 30; placebo 32 Number of withdrawals/dropouts: 4 from guanfacine group (2 lack of efficacy, 2 AEs); 4 from placebo group all due to lack of efficacy Gender: 26/30 male in guanfacine group; 27/32 male in placebo group Mean age: 8.4 years IQ: not reported Baseline ABC‐I or other BoC: guanfacine ABC‐I 20.3; placebo 18.06 Concomitant medication: not reported Previous medications: not reported
Interventions	Intervention (guanfacine) for 8 weeks: starting dose for all children was 1 mg/day. Children < 25kg remained on 1 mg/day until day 14 and then increased to 2 mg/day until day 28, and increased again to 3 mg/day for the remaining 4 weeks. Children 25 kg or more increased to 2 mg/day at day 7 up to a maximum of 4 mg/day by day 21 or 28 of the trial. Comparator (placebo) for 8 weeks: placebo administered for up to 8 weeks
Outcomes	Primary outcomes: Irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessment: weekly for the first 4 weeks, then week 6 and week 8
Notes	Study start date: December 2011 Study end date: March 2014 Source of funding: "supported by NIMH grants to Dr. Scahill (R01MH083707), Dr. McDougle (RO1MH83739), Dr.McCracken (RO1MH083747), and Dr. King (R01MH86927); by a Yale Clinical and Transitional Science Award (UL1 RR024139) from the NIH National Center for Research Resources; and by Atlanta Clinical and Translational Science Institute, Emory University, which is supported by the NIH National Center for Advancing Translational Sciences under award UL1TR000454. Shire Pharmaceuticals provided active extended‐release guanfacine and placebo." Conflicts of interest: none declared Trial registry: NCT01238575
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Unclear risk	Quote: "Using permeated blocks to conceal allocation, eligible subjects were randomly assigned within site without stratification in a 1:1 ratio to extended‐release guanfacine or placebo for 8 weeks."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Two blinded clinicians followed each subject: a treating clinician and an independent evaluator....To protect the blind, the independent evaluator did not discuss adverse effects or dosing".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The treatment mask was broken for subjects who did not show a positive response. The blind was broken by the treating clinician, and treatment status was not disclosed to independant evaluators"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Consort diagram was provided outlining numbers at each stage of the trial, including the number analysed and number that completed the trial. All randomly assigned participants were included in the ITT analyses.
Selective reporting (reporting bias)	Unclear risk	Although the ABC‐hyperactivity was the primary outcome measure, other secondary measures such as the CGI were not reported.
Other bias	Unclear risk	Shire pharmaceuticals provided active extended‐release guanfacine and placebo.