Researchers working in the field of clinical trials for addictive disorders have discussed whether the use of responder analyses (analyses which compare the proportion of patients in each treatment arm who achieve the desired response) in these trials represents "setting the bar too high." These discussions involve assumptions about the relative ease or difficulty of establishing a treatment effect using group means versus doing so using responder analyses. In (placeholder for title of McCann paper, Ref. 1), the authors have shown that using a responder analysis identified a treatment effect in methamphetamine dependence, which an initial analysis of group means did not. This demonstrates that responder analysis may be a more appropriate approach, and depending on the study design, may demonstrate differences not appreciated by group means. Other authors have also identified situations in which a responder approach demonstrates an effect where group means did not [2], or where a comparison of means yielded equivocal results of uncertain clinical significance [3]. In addition, Falk et al. [4] recently compared the use of a responder analysis to customarily used group mean comparisons in alcoholism trials and found that their responder definition was as sensitive as customary measures in detecting treatment effects.Addictions are behavioral disorders, characterized by compulsive self-administration of substances despite physical and psychosocial consequences. Although considerable attention is given in addiction trials to biological measures of drug use as endpoints, cocainuria or methamphetaminuria is only a marker and not the disorder under treatment. The aim of treatment is often expressed as an effort to modifying patients' drug use behavior, but the desired effect is improvement in physical and psychosocial consequences. Changing the behavior only minimally, without having impact on the consequences, would be pointless. Drug-taking behavior observed during the brief window of a clinical trial is a surrogate endpoint, as trials intended to show effects on physical or psychosocial consequences of drug use would need to be very long and very large, and may be impractical. When drug-taking behavior is used as a surrogate endpoint, there should be a demonstration of change in behavior that can be reasonably predictive of improvement, such as avoidance of alcohol-related health and social consequences.

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