A meta-analytic model for integrating outcomes in drug research: Subjective effects of phenylpropanolamine related to abuse potential

Concern about the potential for adverse stimulant-type effects associated with the widely used over-the-counter (OTC) medication, phenylpropanolamine hydrochloride (PPA), has resulted in a number of carefully controlled clinical studies of its effect on humans. Doses studied have ranged up to three times the recommended dose for OTC appetite suppressants. These trials have used a standardized methodololy that allows a comparison of PPA effects relative to placebo for standardized measures of amphetamine-like effect (the Addiction Research Center Inventory [ARCI] A-Scale) and for measures of euphorigenic effect (the ARCI MBG-Scale). We review the recent clinical trial literature on subjective effects of PPA, first from a qualitative/narrative point of view and then using a meta-analytic approach that emphasized a quantitative evaluation of magnitude and homogeneity of effects. Both of these approaches to knowledge synthesis suggest that PPA is not reliably distinguishable from placebo in terms of the subjective effects that are known to be related to the abuse potential of stimulant drugs. These results suggest that the general absence of stimulant-type abuse potential in the original investigations that examined the subjective effects of PPA can not be due simply to a lack of statistical power to find such effects. This article illustrates how the statistical technique of meta-analysis can be applied to help summarize data involved in drug development and to make regulatory decisions regarding a behaviorally defined safety endpoint.