NCT03242772.

Study characteristics
Methods	11‐week parallel trial of amphetamine plus parent training versus placebo plus parent training
Participants	Inclusion criteria: children 3‐10 years parent or legal guardian consents and is willing to comply with all study procedures and is available for the duration of the study diagnosed with both ASD and ADHD based consensus diagnosis informed by results of the ADOS‐2, ADI‐R, and a Standardized ADHD Diagnostic Interview and the MINI psychiatric diagnostic interview in good general health as evidenced by medical history and physical exam and review of safety labs and ECG Exclusion criteria: recent use of prohibited psychoactive medication in close proximity of baseline assessments known allergic reactions to amphetamines known history of or personal history of sudden non‐ischaemic cardiac death in a first or second degree family member (sibling, parent, aunt, uncle, cousin or grandparent) or significant cardiac abnormalities or disease inability of the caregiver participating in P‐ESDM and responding to questionnaires to fluently speak English presence of any psychiatric conditions or psychiatric symptoms in addition to ASD and ADHD History of epilepsy or seizure disorder (except for history of simple febrile seizures or if the child is seizure free (regardless of seizure type) for the past year) Location/setting: Duke Center for Autism and Brain Development, USA Number of withdrawals/dropouts: amphetamine group 3 dropped out (2. LTFU, 1 withdrew); placebo group 1 dropped out due to "physician decision" Gender: 12 male, 6 female Mean age: intervention group 86.83 (SD20.80) months; placebo group 103.00 (18.88) months IQ: not reported Baseline ABC‐I scores or other BoC: not an outcome Concomitant medications:details not provided History of previous medications: details not provided
Interventions	Intervention: amphetamine: administered in the morning. Treatment initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses flexibly titrated upward and "may be decreased or stopped at any time." Parent training: all participants receive 8 weekly parent‐child therapy sessions. Sessions delivered by a therapist trained in parent coaching and Early Start Denver Model principles and strategies, and utilising a therapy manual (includes coaching for behaviour management and handouts) Comparator: placebo: matched placebo tablets administered in the morning and provided for 11 weeks. Tablets "titrated in the same way as the active drug and may be stopped at any time." Parent training: all participants receive 8 weekly parent‐child therapy sessions. Sessions delivered by a therapist trained in parent coaching and Early Start Denver Model principles and strategies, and utilising a therapy manual (includes coaching for behaviour management and handouts)
Outcomes	Primary outcomes: adverse effects Secondary outcomes: none reported Timing of outcome assessments: 11 weeks (endpoint)
Notes	Study start date: December 2018 Study end date: results submitted online December 2021 Funding: Duke University Conflicts of interest: details not provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Only information "Allocation: Randomized"
Allocation concealment (selection bias)	Unclear risk	Only information "Allocation: Randomized"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No information apart from, "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information apart from, "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)"
Incomplete outcome data (attrition bias) All outcomes	High risk	Primary outcome data not reported. "This variable required behavioral coding of videotaped caregiver‐child interactions collected at two time points. This coding were not conducted due to the fact that the study was terminated and time 2 data were not collected for participants due to safety concerns related to Covid‐19."
Selective reporting (reporting bias)	High risk	Primary outcome data not reported. "This variable required behavioral coding of videotaped caregiver‐child interactions collected at two time points. This coding were not conducted due to the fact that the study was terminated and time 2 data were not collected for participants due to safety concerns related to Covid‐19."
Other bias	Low risk	"Principal Investigators are NOT employed by the organization sponsoring the study." "There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed."