Danfors 2005.

Study characteristics
Methods	6‐month cross‐over trial of tetrahydrobiopterin versus placebo
Participants	Inclusion criteria: a diagnosis of ASD according to the DSM‐4 aged 3‐7 years an age‐adjusted IQ score of ≥ 30 on Griffiths Developmental Scale cerebrospinal fluid tetrahydrobiopterin < 30 pmol/mL Exclusion criteria: no previous history of asthma or epilepsy no previous pharmacological treatment against ASD IQ < 30 Location/setting: outpatients from 4 different departments of child and adolescent psychiatry in Sweden Sample size: 12 in total Number of withdrawals/dropouts: "all 12 children completed the tetrahydrobiopterin treatment study". Gender: 11 male, 1 female Mean age: 5.3 years IQ: 32‐93 Concurrent medications: participants could not have taken pharmacological treatments for ASD prior to or during the study. History of previous medications: see above
Interventions	Intervention (tetrahydrobiopterin): individual doses of tetrahydrobiopterin at 3 mg/kg of body weight were prescribed in capsule form (in single‐dose pack) to be taken twice daily. Comparator (placebo): twice‐daily capsules
Outcomes	Primary outcomes: adverse events Secondary outcomes: none reported
Notes	Study start date: details not provided Study end date: details not provided Funding: "This research was supported by grants from the Subfemtomole Biorecognition Project, ICORP, Japan Science and Technology Agency (JST), The Swedish Research Council (grant 8645) the Sven Jerring Fund, Holmia insurance company, the Gillbergska Foundation, the Samaritan Foundation, the Linnea and Josef Carlssons Foundation, and the child‐neurology fund of Uppsala University" Conflicts of interest: none declared Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The local hospital pharmacy produced the capsules and performed the randomisation of the patients
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind; the assessors remained blinded throughout the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind; the assessors remained blinded throughout the study.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	AEs were not provided for both groups despite being recorded every 3 months.
Selective reporting (reporting bias)	Unclear risk	Difficult to determine without a protocol
Other bias	Low risk	None identified