Handen 2008.

Study characteristics
Methods	Cross‐over trial of guanfacine versus placebo
Participants	Inclusion criteria: diagnosis of intellectual disability (based on the most recent school psychological assessment) and/or autism (ASD or pervasive developmental disorder) diagnosed with ADHD or present with clinically significant deficits in the areas of overactivity and inattention scored ≥ 15 points on the CPRS/or Teacher Hyperactivity Index Exclusion criteria: any known genetic disorders continued current use of prescribed stimulant medications Location/setting: outpatient speciality clinic serving children with developmental disorders Sample size: 11 in total Number of withdrawals/dropouts: 1 from placebo group due to non‐compliance Gender: 10 male, 1 female Mean age: 7.3 years IQ: cognitive functioning ranged from severe intellectual disability to average IQ. Baseline ABC‐I or other BoC: details not provided Concomitant medications: Adderall (2), mirtazapine (1); risperidone, zolpidem, tartrate and carbamazepine (1); nortriptyline (1); lamotrigine (1); methylphenidate (1); and bupropion and clonidine (1) History of previous medications: details not provided
Interventions	Intervention (guanfacine): began on a maximum of 3.0 mg/day titrated doses over a 19‐day period. After 8 days on the highest dose, a 6‐day washout period commenced (1.5 mg/day for 3 days and 0 mg/kg per day for 3 days) Comparator (placebo): equivalent placebo for 8 days
Outcomes	Primary outcomes: irritability, measured using the parent‐rated ABC‐I subscale (Aman 1985) Secondary outcomes: tolerability Timing of outcome assessments: baseline then at 4 additional visits
Notes	Study start date: not reported Study end date: not reported Source of funding: not reported Conflicts of interest: not reported Trial registry: not reported
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	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided, only that it is a double‐blinded trial
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details not provided
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "we did not have complete sets of parent and/or teacher data for some subjects (e.g., one parent whose child was in the summer program was unreliable in completing questionnaires; some trials that occurred across a school vacation resulted in incomplete teacher data). Our solution was to use parent data as our primary source when available and to use teacher data if parent data were missing."
Selective reporting (reporting bias)	High risk	The authors note that the ABC was measured at baseline and an additional four visits. Neither baseline nor additional visit scores were recorded.
Other bias	High risk	Quote: "no standardized instruments were used to assess autistic disorder and comorbid psychiatric diagnoses" (among other limitations)