In the last years, several new drugs were withdrawn from the market, or their approval was either postponed or rejected, mostly for safety reasons. Serious adverse events were found to be the sixth most important cause of death in hospitalised patients in the USA. Mibefradil (Posicor) was withdrawn because of side effects caused by interactions with many cardiovascular drugs, based on common biotransformation via cytochrome P450 isoenzymes. Moreover, the prolongation of the QT-interval and of QTc (LQTS) was found in two cases reported here and two syncopes appeared in patients on Posicor. This effect might have been overlooked, disregarded or underestimated in preclinical trials. The main disadvantage of big multicenter studies is the heterogeneity of populations compared, caused by ethnic and other individual differences, the instability of some criteria used, and the manifold concomitant medication. This disparity is a limiting factor of internal and external validity: only a small part of patients recruited into the study can be evaluated: 7% in SOLVD, 1% in SHEP and 19,4% in EPICAL study. Consequently, the results are not applicable to some special groups of patients and have only a limited predictive value for the management of individual patients.

        Key words: clinical studies - heterogeneity of population, validity of results, drug interactions, QT-interval, LQTS. J.