Oncken 2006
| Methods | Country: USA Setting: 10 research centres Aim: To evaluate efficacy and safety of 4 varenicline dose regimens Dates conducted: Not stated Study Design: Phase 2 double‐blind placebo‐controlled RCT Analysis: Power calculation (90%, 2‐tailed, alpha = 0.05); Logistic regression with treatment and centre as independent variables. Likelihood ratio Chi² statistic |
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| Participants | 647 healthy volunteer smokers, aged 18 ‐ 65, smoking at least 10 CPD. 49.5% men, 80% white, av CPD 21, mean FTND 5.5. Allocated to group 1 (129), group 2 (130), group 3 (129), group 4 (130) or placebo (129) Exclusion criteria: Standard pharmacotherapy trial criteria, + use of NRT or bupropion within last 3m; use of marijuana or tobacco other than cigarettes with last month. | |
| Interventions | 1. 0.5 mg nontitrated (2/day for 12 wks) 2. 0.5 mg titrated (wk1 1/day, wks 2 ‐ 12 2/day) 3. 1.0 mg nontitrated (2/day for 12 wks) 4. 1.0 mg titrated (0.5 mg 1/day for 3 days, 0.5 mg 2/day for 4 days, 1.0 mg 2/day wks 2 ‐ 12) 5. placebo tablets 2/d 12 wks All groups received self‐help booklet at baseline, + brief (≤ 10 mins) counselling at weekly clinic visits throughout treatment phase, and phone call 3 days post‐TQD. At each visit smoking status reported and CO verified; vital signs, weight and adverse events. Urine, blood tests and ECGs at screening, baseline, wks 1, 2, 4, 7 and 12. Follow‐up phase: smoking status + CO measured at wks 13, 24, 52; self‐reported status by phone at wks 16, 20, 28, 32, 36, 40, 44 | |
| Outcomes | Primary outcome: Continuous verified 4‐wk abstinence at wks 4 ‐ 7 and 9 ‐ 12 Secondary outcomes: Continuous verified abstinence at wks 2 ‐ 12 and 9 ‐ 52; 7‐day PPA throughout treatment phase and at wks 12, 24 and 52 Other outcomes: weight change; craving and withdrawal changes using MNWS and mCEQ; adverse events Validation was by expired CO ≤ 10 ppm Cessation analyses were ITT (all participants randomised), while tolerability and safety analyses were based only on those known to have used the intervention drug (N = 627). Attrition was 27% during treatment phase, and 22% of follow‐up consenters lost in follow‐up phase | |
| Treatment type | Medication: VARENICLINE | |
| Notes | For cessation analyses, titrated and nontitrated results were reported separately and pooled. 24‐wk continuous cessation data supplied by authors The trial was funded by Pfizer Inc | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not stated |
| Allocation concealment (selection bias) | Unclear risk | "Eligible subjects were randomly assigned to 1 of 5 groups" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "Subjects and investigators were blinded to the study drug treatment [, and] were not encouraged to guess their treatment assignment" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Missing COs or visits OK if confirmed abstinent before and after missed measure |
| Selective reporting (reporting bias) | Low risk | All expected and predicted outcomes covered |
| Other bias | Unclear risk | None noted |