West 1991.

Study characteristics
Methods	Cluster‐randomised study in rural Nepal
Participants	Eligibility: children aged 0–5 years; children with xerophthalmia Excluded: children who had recently participated in a vitamin A programme Sample: 28,630 children in 261 clusters. 51.3% boys
Interventions	Experimental group I: vitamin A 100,000 IU for children aged 6–11 months and 200,000 IU for children aged ≥ 12 months administered 1–3 times + vitamin E 40 IU Experimental group II: very low dose vitamin A (1000 IU) + vitamin E 40 IU Study duration: 16 months
Outcomes	Mortality, cause‐specific mortality, Bitot's spots, night blindness, xerophthalmia
Notes	ICC not disclosed, although study estimates reported to have been adjusted for the unit of allocation. Study had additional recruitment phases in second and third treatment cycles. 1807 children at 4 months and 2018 children at 8 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "After blocking on the local development area, the 261 wards were randomly assigned to receive vitamin A supplementation or placebos at 4‐month intervals". Comment: inadequately described to permit judgement.
Allocation concealment (selection bias)	Unclear risk	Quote: "Both the investigators and communities were masked to the random assignment". Comment: study was a cluster‐designed trial and there was insufficient information to determine whether allocation occurred before or after treatment group assignment was known.
Blinding (performance bias and detection bias) Blinding of participants	Low risk	Quote: "The supplements were given as single‐dose gelatin capsules of identical taste and appearance".
Blinding (performance bias and detection bias) Blinding of provider	Low risk	Comment: as above; probably done.
Blinding (performance bias and detection bias) Blinding of outcome assessor	Low risk	Comment: as above; probably done.
Incomplete outcome data (attrition bias)	Unclear risk	Quote: "All analyses were carried out on an intention‐to‐treat basis. Computed mortality rates were based on child‐years of observation". Quote: " … all children living in wards which received high dose vitamin A every 4 months were considered to have been treated with vitamin A, and all children living in wards which received placebo were considered 'untreated' ". Comment: the rates of withdrawal were balanced between groups and the data were analysed based on patient‐years of observation. The unclear reasons for withdrawals, variable duration of follow‐up due to more than recruitment cycle and the low rate of mortality in relation to the withdrawal rates mean that it is uncertain whether the study was at risk of attrition bias.
Selective reporting (reporting bias)	Low risk	Comment: complete data for all time points were available for the review. The last available observation reported in a follow‐up article gave an RR for mortality slightly higher than that for the 12‐month data given in the primary study report (0.74 versus 0.7).
Other bias	Low risk	Comment: a method for estimating the ICCs was reported in Katz 1995.

ALRI: acute lower respiratory illness; BMI: body mass index; CENSIA: Centro Nacional para la Salud de la Infancia y la Adolescencia; CI: confidence interval; CMCH: Christian Medication College & Hospital; HPLC: high‐performance liquid chromatography; ICC: intracluster correlation coefficient; LRTI: lower respiratory tract infection; RAND: a function in Excel, which is used to generate a random number; RDA: recommended dietary allowance; RR: risk ratio; RSV: respiratory syncytial virus; VAD: vitamin A deficiency; VAS: vitamin A supplementation; WHO: World Health Organization.