West 1991.

Methods	Cluster‐randomised study in rural Nepal
Participants	Eligibility: children aged between 0 and 5 years were eligible for the study. Children with xerophthalmia were included. Children who had recently participated in a vitamin A programme were excluded from the study. Sample: 28,630 children in 261 clusters were recruited. 51.3% of participants were boys
Interventions	Vitamin A (100,000 IU for 6‐11 months and 200,000 IU for children 12 months and older) administered 1‐3 times was compared with a very low dose of vitamin A (1000 IU). Both supplements contained 40 IU vitamin E. 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 and 2018 children entered at 4 and 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 judgment.
Allocation concealment (selection bias)	Unclear risk	Quote: "Both the investigators and communities were masked to the random assignment." Comment: the study was a cluster‐designed trial and there was insufficient information to determine whether allocation took place 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 the treatment 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 is 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 a 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 illnesses;BMI: body mass index; CENSIA: Centro Nacional para la Salud de la Infancia y la Adolescencia; CI: confidence interval; CMCH: Christian Medication College & Hosptal; HPLC: high performance liquid chromatography; ICC: intra‐cluster correlation coefficient; RAND: a function in Excel, which is used to generate a random number; RDA: recommended dietary allowance; RR: risk ratio; RSV: respiratory syncytial virus; WHO: World Health Organization.