Adverse drug effects and the controlled clinical trial

Summary

The controlled clinical triad is designed not to discover new drug effects, but to verify those effects, about which prior knowledge exists adequate for formulating exact null hypotheses. Therapeutic effects always meet this requirement. The question of a drug's clinical toxicity is essentially vague and open-ended and, therefore, ineligible for being fully answered by controlled trial. It can examine only those adverse drug effects which are predicted or anticipated, which occur with a certain frequency compatible with a practical trial size, and which do not pose ethical restrictions to human experimentation. Most toxic drug effects must be assessed empirically, i. e., by incompletely controlled observation or survey of events as they happen during ordinary drug use. This does not mean arbitrary collection of isolated data, but requires purposeful, systematic and coordinated procedures. Observational evidence is circumstantial and disputable from a strictly scientific viewpoint. Nevertheless, if observational data satisfy certain criteria, they contribute to decisions which are reasonable and practically useful by minimizing the risks for patients from adverse drug effects.