Plummer 2007Low.

Methods	Randomized, double‐blind, placebo‐controlled, primary‐prevention trial with parallel group design.
Participants	Country: Venezuela Number of participants randomised: 1980, aged 35 to 69 years, 52.7% females. Inclusion criteria: population at high risk for stomach cancer in general good health, and permanent residents of Tachira State. Exclusion criteria: serious illness, including any type of cancer, those whose mental status made long‐term adherence to the treatment regimen unlikely and pregnant women.
Interventions	Participants were randomly assigned to receive: group 1: vitamin C (750 mg), vitamin E (600 mg), and beta‐carotene (18 mg) (n = 990); group 2: placebo (n = 990); daily for 3 years. The treatment was taken in the form of three capsules per day, one with each of the three main meals. Each capsule contained 250 mg vitamin C, 200 mg vitamin E, and 6 mg of beta‐carotene, for a daily dose of 750 mg of vitamin C (12.5 times the recommended daily allowance), 600 mg vitamin E (20 times the recommended daily allowance), and 18 mg beta‐carotene (considered the maximum dose if carotenoderma is to be avoided).
Outcomes	The primary outcome of the trial was the progression and regression of precancerous lesions of the stomach, as determined by histologic findings.
Notes	Compliance for the intervention group was confirmed by the pill counts and measuring the biochemical markers of supplementation. Excellent compliance was indicated by pill counts when participants returned for their vitamin pills: 91% of all containers were returned with less than 10% of pills. There were clear increases in beta‐carotene and vitamin E levels in the treated group beyond the levels observed at baseline. In the placebo group, by contrast, no changes were observed. Participants who did not return for their supply of capsules were contacted first by telephone, then visited at home by social workers who enquired about the reasons for nonattendance, encouraged continuing participation, and provided the next month's supply of capsules. Overall 302 participants from active and 278 participants from placebo group dropped‐out during the trial. The number of participants who dropped out was slightly higher in the vitamin group than in the placebo group, but the difference was not statistically significant (P = 0.14, for difference of two proportions). Both vitamin capsules and placebo were supplied by Hoffman‐La Roche.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by a central and independent randomisation unit, so that intervention allocations could not have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.