Kirschner 2014.

Methods	Randomised, double‐blind, placebo‐controlled cross‐over trial
Participants	20 participants with SMA types II and III, genetically confirmed with SMN1‐ deletion or mutation, aged 6–36 years Inclusion criteria: 6–36 years of age, genetically confirmed diagnosis of SMA verifying SMN1 deletion or mutation types II or III SMA (independent sitting is or was possible) the physical ability to co‐operate on assessment of at least the primary outcome measure Exclusion criteria: diagnosis of growth hormone deficiency treatment with any medication that could potentially affect muscle strength within 8 weeks prior to trial onset pregnancy, lactation or if the woman was of child‐bearing age and sexually active without verified contraception participation in another clinical trial within 3 months of trial starting any contraindication for growth hormone treatment
Interventions	Subcutaneous somatotropin (first week dose 0.015 mg/kg/day; week 2–12 dose 0.03 mg/kg/day) or placebo subcutaneous (first week dose 0.015 mg/kg/day; week 2–12 dose 0.03 mg/kg/day) Treatment of 12 weeks with 1 treatment (somatropin or placebo) followed by 8 weeks' washout, afterwards second cross‐over treatment period (somatropin or placebo) of 12 weeks is started
Outcomes	Change in quantitative muscle strength of upper limb using hand‐held myometry in elbow flexion and handgrip, change in quantitative muscle strength of lower limb, muscle strength with MMT in 7 muscles, change in motor function (HFMSE), change in Gowers' time, change in qualitative Gowers' manoeuvre, change in pulmonary function (FVC and peak cough flow), adverse events
Funding	Quote: "NovoNordisk Pharma GmbH provided the trial drug and some financial support for conducting this trial. NovoNordisk had no influence on the trial design, how the trial was conducted or the data analysis."
Conflicts of interest	Author conflicts of interest not stated
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned. Computer‐generated allocation by central pharmacy.
Allocation concealment (selection bias)	Low risk	Computer‐generated allocation by central pharmacy.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants, physicians and physiotherapists were blinded. Statistical analysis of primary outcome was blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participants, physicians and physiotherapists were blinded. Statistical analysis of primary outcome was blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	3 participants withdrew during somatotropin treatment. They were included in the modified ITT (unknown method) analysis.
Selective reporting (reporting bias)	High risk	Quality of life is mentioned as an outcome, but no scale is mentioned. However, the report states that the trial found no difference between somatotropin and placebo groups in quality of life.
Other bias	Unclear risk	Potential bias from cross‐over study design; cross‐over design implies risk of carryover effect.