Mooney 2005Low.

Methods	Randomised, double‐blind placebo‐controlled parallel group trial.
Participants	Country: United States. Number of participants randomised: 284, 55% men and 45% women were aged 18 or older, mean age 36.8 years. Inclusion criteria: men and women ages > 18 years who smoked at least 10 CPD, did not take vitamin supplements or use a nicotine patch in the 3 months before enrolment, had no prior history of cancer or liver disease, lived at a permanent address, owned a home telephone, were willing to comply with the 2‐year protocol, and completed a 1‐month placebo run‐in. Exclusion criteria: none stated.
Interventions	Participants were randomly assigned to receive: group 1: vitamin C 500 mg and vitamin E 400 IU (n = 142); group 2: placebo (n = 142); for a period of 1.25 years.
Outcomes	The primary outcome measure was: level of benzo(a)pyrene [B(a)P]‐DNA adducts as an intermediate cancer risk marker.
Notes	Treatment compliance was assessed by serum vitamin measurements and pill counts. Compliance with treatment did not differ by gender measured by blood levels of {alpha}‐tocopherol at 15 months of follow‐up or by pill counts. At all time points after randomisation, in all participants, the treatment group had significantly higher levels of vitamin E than the placebo group. However, in women, the blood levels of vitamin E did not plateau until the 9‐month time point. Eighty‐three of 142 (58%) in the treatment group and 93 of 142 (66%) in the placebo group completed 15 months of treatment. Trial agents were provided by Hoffman‐LaRoche.
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.