title: An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.
abstract: BACKGROUND
  Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing.
  
  
  OBJECTIVE
  This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil.
  
  
  RESULTS
  This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation).
  
  
  CONCLUSIONS
  A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.
authors.affiliation: Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA, perkinska@upmc.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D016642:Bupropion / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D018592:Cross-Over Studies; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D006801:Humans; D011810:Quinoxalines / Q000627:therapeutic use; D012107:Research Design; D016540:Smoking Cessation / Q000379:methods*; D054928:Validation Studies as Topic; D000068580:Varenicline
chemical_list: D018687:Antidepressive Agents, Second-Generation; D001552:Benzazepines; D011810:Quinoxalines; D016642:Bupropion; D000068580:Varenicline