Tzeng 2000.

Methods	Randomised (ratio 2:1), placebo‐controlled, double‐blind trial
Participants	9 participants who fulfilled international classification criteria for SMA types II or III Inclusion criteria: aged 4–10 years, confirmation of chromosome 5q SMN gene deletion parent or guardian willing and able to comply with study requirements and give consent participant willing to comply with the study Exclusion criteria: history of epilepsy concurrent participation in another investigational drug trial or participation in 1 during the previous 30 days abnormal serum chemistries in the initial screening the inability to rapidly contact or be contacted by the investigator in case of emergency
Interventions	Thyrotropin‐releasing hormone 0.1 mg/kg intravenous once a day or placebo Duration of treatment: 29 days of treatment over a 34‐day period Follow‐up: 35 days
Outcomes	Change in muscle strength (dynamometry), adverse events
Funding	Quote: "Supported, in part, by Ferring Laboratories, Inc., Suffern, New York, the manufacturer of Thyrel™ who made the study medication, Thyrel™, available without cost to the subjects, and, in part, by grant H133 P 70011, Advanced Multidisciplinary Fellowship in Rehabilitation Outcomes Research to the Department of Physical Medicine and Rehabilitation, UMDNJ‐New Jersey Medical School, from the National Institute on Disability and Rehabilitation Research."
Conflicts of interest	Not reported
Notes	Groups were not equal at baseline, with only women, only SMA II and older participants in the placebo group. Muscle strength was measured bilaterally of deltoid, biceps, triceps, wrist extension, hand grip, hip flexion, knee extension and knee flexion.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned (2:1). Patients randomised by double coin flip for each patient. Any heads‐tails combination was a participant; a tails–tails combination was a control; and a heads–heads combination was rejected and the flip repeated. Potential bias by inclusion of first arrival method. Quote: "Once either the control or subject group was full, all subsequent arriving patients were placed into the remaining group."
Allocation concealment (selection bias)	High risk	Randomisation done on a first arrival basis. Quote: "Once either the control or subject group was full, all subsequent arriving patients were placed into the remaining group."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All investigators and participants were blinded. Only the pharmacist was unblinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All investigators and participants were blinded. Only the pharmacist was unblinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts.
Selective reporting (reporting bias)	High risk	All outcomes were reported. The statistical analysis plan is limited and unclear.
Other bias	Low risk	None identified.