EFFECT AND EFFICACY - ON THE FUNCTION OF MODELS IN CONTROLLED PHASE-III TRIALS AND THE NEED FOR PROSPECTIVE PHARMACOEPIDEMIOLOGIC STUDIES

While the ''effect'' of a drug can be observed or deduced from observa tional data, the concept of ''therapeutic efficacy'' represents mainly a theoretical construction of a high degree of abstraction which is i nconceivable without reciprocal combination with other theoretical con structs. The ''therapeutic efficacy'' of drugs can be investigated onl y via clinical-pharmacological or clinical ''models''. Several example s are given and discussed against the background of the actual conside rations for shortening phase III studies and extending pharmacoepidemi ological phase IV studies for scientific, practical and economic reaso ns. Of special relevance is the question whether study data of phase I II allow an extrapolation to the wider patient population which it is intended to treat. Thus, it is well known that the criteria for repres entativeness in the investigated population are rarely achieved in pha se III studies. Furthermore, observations have shown that various inte rvening moderator variables, such as the investigated subgroup or the trial setting (e.g. inpatient or respectively outpatient treatment), m ight influence therapeutic efficacy and the possibility of generalizin g the results. This again raises the crucial question of clinical rele vance of significant effects. Possible ways of overcoming this unsatis factory situation are suggested.