Levin 1961.

Methods	Randomised double‐blind placebo‐controlled study of parallel design. Single‐centre trial in the USA. Duration 6 months, planned to see participants every 2 months when possible. No efforts made to counterbalance groups from which individuals were lost during study.
Participants	49 participants accepted with proven diagnosis of CF and stabilised; 45 children followed for at least 2 months; 37 completed 6 months (18 in treatment group; 19 in placebo group). Each participant rated independently by 2 observers as to condition at the beginning of study on an arbitrary scale (1 = good condition up to 5 = very severe illness). Tocopherol Group 20 participants, mean (SD) age 113.1 (65.12) months, 9 males and 11 females, mean (SD) illness severity score 2.22 (1.09), mean (SD) weight 24.3 (9.75) kg. Placebo Group 25 participants, mean (SD) age 113.5 (63.99) months, 17 males and 8 females, mean (SD) illness severity score 2.10 (0.913), mean (SD) weight 26.8 (12.0) kg.
Interventions	10 mg/kg/day of vitamin E tocopherol (d‐l alpha‐tocopheryl acetate) in water‐miscible solution in 2 or 3 divided doses (n = 20) versus placebo (n = 25).
Outcomes	Weight, muscle power, serum tocopherol, activity of S‐GOT in serum and subjective improvement.
Notes	Reported data at baseline, 2 and 6 months Tocopherol and placebo provided by U.S. Vitamin Corporation. Supported in part by grants from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Public Health, Public Health Service and the Muscular Dystrophy Associations of America. Limited information on the basis for diagnosis of CF. The study does not clarify whether the participants were pancreatic sufficient or insufficient.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed as follows: cards labelled 1 or 2 were individually placed in sealed envelopes in groups of 4 (2 for each mixture number). Envelopes were divided into 3 groups, according to age of participants: < 5 years, 5 ‐ 10 years, and ≥ 10 years and over. Each child accepted into the study group was assigned an envelope from the appropriate age group, and the enclosed card indicated the mixture to be given.
Allocation concealment (selection bias)	Low risk	Sealed envelopes with designated randomisation, each child accepted into study was assigned an envelope from the appropriate age group.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	From the paper in plan of study: "Patients and testers did not know which preparation was taken" (double‐blind method) also stated "Physicians blind to vitamin E results".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Out of the initial 49 participants accepted, 37 completed the study but intention‐to‐treat analysis was not carried out. 3 died within 6 months (all in placebo group), 2 declined to continue medication after 2 months, 1 participant removed due to diabetes mellitus and 7 participants studied for less than 6 months. However, we feel the attrition is balanced among the two groups; hence we judged this study to have a low risk of bias. Planned to measure data at baseline, end of study (6 months) and every 2 months where possible, reported data at baseline, 2 and 6 months.
Selective reporting (reporting bias)	Unclear risk	Protocol not available, but the paper reports data for each outcome measurement listed in the 'Methods' section of the paper.
Other bias	Unclear risk	None identified. Limited information on the basis for diagnosis of CF and whether pancreatic sufficient or insufficient.