title: Evidence of nicotine replacement's effectiveness dissolves when meta-regression accommodates multiple sources of bias.
abstract: To accommodate and correct identifiable bias and risks of bias among clinical trials of nicotine replacement therapy (NRT).
  
  
  
  Meta-regression analysis of a published Cochrane Collaboration systematic review of 122 placebo-controlled clinical trials.
  
  
  
  Both identified risks of bias and potential publication (or reporting or small sample) bias are associated with an increase in the reported effectiveness of NRT. Whenever multiple sources of biases are accommodated by meta-regression, no evidence of a practically notable or statistically significant overall increased rate of smoking cessation remains. Our findings are in stark contrast with the 50% to 70% increase in smoking cessation reported by the Cochrane Collaboration systematic review.
  
  
  
  After more than 100 randomized clinical trials have been conducted, the overall effectiveness of NRT is in doubt. Simple, well-established meta-regression methods can test, accommodate, and correct multiple sources biases, often mentioned but dismissed by conventional systematic reviews.
authors.affiliation: Department of Economics, Hendrix College, 1600 Washington, Conway, AR 72032, USA; Faculty of Arts and Education, Deakin University, 221 Burwood HWY, Burwood, Victoria 3125, Australia. Electronic address: Stanley@hendrix.edu.
authors.forename: T D
authors.initials: TD
authors.lastname: Stanley
authors.affiliation: Oklahoma State University, College of Osteopathic Medicine, 1111 W. 17th St, Tulsa, OK 74107, USA.
authors.forename: Shelby
authors.initials: S
authors.lastname: Massey
mesh_terms: D015982:Bias; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016540:Smoking Cessation / Q000379:methods* / Q000706:statistics & numerical data*; D061485:Tobacco Use Cessation Devices / Q000706:statistics & numerical data*; D016896:Treatment Outcome
keywords: Egger regression; Meta-regression; Nicotine replacement therapy; Precision-effect test; Publication bias; Risks of bias