CEASE 1999.

Study characteristics
Methods	Study design: factorial RCT Country: multicentre ‐ 36 clinic centres in 17 European countries Recruitment: community volunteers
Participants	3575 smokers (> 14 cigarettes per day) 52% men, average age 41, average cigarettes per day: 27 (34% had previously used NRT)
Interventions	Factorial design compared 2 patch doses and 2 treatment durations. Dose 15 mg or 25 mg (16‐hour), duration of active treatment 28 weeks (including 4‐week fading) or 12 weeks (including 4‐week fading) 1) 25 mg patch for 28 weeks 2) 25 mg patch for 12 weeks 3) 15 mg patch for 28 weeks 4) 15 mg patch for 12 weeks 5) Placebo
Outcomes	Prolonged abstinence at 12 months, sustained from week 2 Validation: expired CO < 10 ppm at each clinic visit Adverse events: SAEs measured during whole study period, but cardiac AEs reported within 8‐week treatment period
Notes	Level of support reclassified to high for 2007, because of repeated visits. Limited support at these visits This study was sponsored by Pharmacia and Upjohn Conflicts of interest: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated allocation list was prepared centrally and allocated subjects to treatment numbers". Randomisation stratified by centre
Allocation concealment (selection bias)	Low risk	See process above
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Active and placebo patches were identical in appearance and packaging. In order to maintain blinding, all subjects continued to use two patches for a total of 26 weeks"; i.e. non‐tapered groups were switched to placebo patches
Incomplete outcome data (attrition bias) All outcomes	Low risk	22% lost to 12‐month follow‐up, and 54% withdrew