title: Improving efficiency of initial tests for efficacy in smoking cessation drug discovery.
abstract: BACKGROUND
  One obstacle to rapid development of new smoking cessation medications is the inefficient early clinical evaluation of the efficacy of novel drugs, which inform us as to whether or not to proceed with the greater expense and time of more formal clinical trials. The vast majority of novel drugs fail to show efficacy for cessation only after substantial resources have been spent and, thus, are largely wasted.
  
  
  METHODS
  The author reviews the general limitations in the current typical procedures for initial tests of cessation efficacy in novel drugs. Small, randomized clinical trials often have good validity but may have practical limitations in achieving adequate statistical power to test novel versus placebo treatment conditions. Lab tests of acute drug effects on abstinence symptoms, during brief enforced cessation periods, are practical but have limited clinical predictive validity.
  
  
  CONCLUSIONS
  Initial efficacy testing may be more efficient if done using innovative crossover designs that evaluate brief 'practice' quit periods for both active and placebo treatments within the same smokers, recruiting those high in quit motivation. Because this approach would require far fewer subjects and a shorter duration of testing, results could be obtained more rapidly and inexpensively to indicate that a novel drug may, or may not, be sufficiently efficacious as to warrant the greater costs and time of formal randomized clinical trials.
authors.affiliation: University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic , 3811 O'Hara Street, Pittsburgh, PA 15213 , USA +1 412 246 5395 ; +1 412 246 5390 ; perkinska@upmc.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D012907:Smoking / Q000188:drug therapy; D016540:Smoking Cessation / Q000379:methods*; D016896:Treatment Outcome
keywords: experimental design; medication screening; nicotine dependence; smoking cessation