RATIONALE: The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to large-scale clinical trials and unpromising drugs do not. Screening procedures for smoking cessation medications either are not sufficiently practical or lack clinical validity. Clinical trials have clinical validity but are often impractical as initial tests of efficacy (i.e., screening) or suffer from limited statistical power. The alternative approach of short-term, laboratory-based studies of purported mechanisms of efficacy may overcome some of the practical problems of clinical trials but appear to have limited clinical validity. OBJECTIVES: This commentary identifies some of the limitations of current short-term screening procedures and provides suggestions for improving such studies. RESULTS: Short-term screening studies typically use smokers unmotivated to abstain (i.e., nontreatment seekers) as participants and examine brief medication effects on clinical markers or potential mechanisms of action, including relief of withdrawal and craving during enforced abstinence or on reduction in the reinforcing effects of smoked tobacco. The limitation of these approaches is shown by their insensitivity to effects of nicotine replacement and bupropion, which are effective in clinical trials for smoking cessation. CONCLUSIONS: The clinical validity of short-term screening studies may improve if these studies simulate some clinical trial procedures within practical limitations. Thus, they should recruit smokers motivated to abstain, emphasize smoking abstinence as a primary index of medication response, examine effects over sufficiently long time periods to encompass the drug's mechanism of action, and assess responses in the natural environment. Whether these changes improve the sensitivity of screening studies is testable. Other research aimed specifically at identifying the mechanisms of therapeutic action of a medication may also profit from using this approach of simulating a short-term clinical trial.
RATIONALE: The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to large-scale clinical trials and unpromising drugs do not. Screening procedures for smoking cessation medications either are not sufficiently practical or lack clinical validity. Clinical trials have clinical validity but are often impractical as initial tests of efficacy (i.e., screening) or suffer from limited statistical power. The alternative approach of short-term, laboratory-based studies of purported mechanisms of efficacy may overcome some of the practical problems of clinical trials but appear to have limited clinical validity. OBJECTIVES: This commentary identifies some of the limitations of current short-term screening procedures and provides suggestions for improving such studies. RESULTS: Short-term screening studies typically use smokers unmotivated to abstain (i.e., nontreatment seekers) as participants and examine brief medication effects on clinical markers or potential mechanisms of action, including relief of withdrawal and craving during enforced abstinence or on reduction in the reinforcing effects of smoked tobacco. The limitation of these approaches is shown by their insensitivity to effects of nicotine replacement and bupropion, which are effective in clinical trials for smoking cessation. CONCLUSIONS: The clinical validity of short-term screening studies may improve if these studies simulate some clinical trial procedures within practical limitations. Thus, they should recruit smokers motivated to abstain, emphasize smoking abstinence as a primary index of medication response, examine effects over sufficiently long time periods to encompass the drug's mechanism of action, and assess responses in the natural environment. Whether these changes improve the sensitivity of screening studies is testable. Other research aimed specifically at identifying the mechanisms of therapeutic action of a medication may also profit from using this approach of simulating a short-term clinical trial.
Authors: Rebecca L Ashare; Rajita Sinha; Rachel Lampert; Andrea H Weinberger; George M Anderson; Meaghan E Lavery; Katherine Yanagisawa; Sherry A McKee Journal: Psychopharmacology (Berl) Date: 2011-09-21 Impact factor: 4.530
Authors: Timothy B Baker; Robin Mermelstein; Linda M Collins; Megan E Piper; Douglas E Jorenby; Stevens S Smith; Bruce A Christiansen; Tanya R Schlam; Jessica W Cook; Michael C Fiore Journal: Ann Behav Med Date: 2011-04
Authors: Dorothy K Hatsukami; Kenneth A Perkins; Mark G Lesage; David L Ashley; Jack E Henningfield; Neal L Benowitz; Cathy L Backinger; Mitch Zeller Journal: Tob Control Date: 2010-10 Impact factor: 7.552