[Use-risk consideration of anti-infective agents from the point of view of the licensing authority].

The present standard requirements for the clinical evaluation of anti-infective drugs are so high that in most cases strong evidence for the benefit of a new medicine can be provided. Therefore risk estimation is much more emphasized than proof of efficacy during the review process performed by the regulatory authority. The total number of patients treated with an investigational drug before an application is made for a product licence varies between 2,000 and 4,000; in rare instances up to 9,000 patients are evaluable. It is obvious that adverse effects with incidences of 0.5% cannot be detected during clinical investigation, even with such a great number of patients. The risk estimation of a new anti-infective drug is based on results from the following sources: toxicity studies in animals, studies on general pharmacology (preclinical and clinical), clinical studies on safety and efficacy, finger-print of adverse reactions of new compounds belonging to approved chemical classes, experience in other countries, and monitoring of safety after licensing. As many drugs share chemical or pharmacological characteristics with approved drugs, the pattern of adverse effects can be anticipated. When reviewing a new anti-infective agent not belonging to an approved chemical class, there remains more uncertainty. In the case of infections for which current treatment exists, the possible risks which can be accepted for a new compound cannot be higher than that of the alternatives. If no alternatives exist, in certain cases high risks can be accepted, especially when a potentially life-saving or life-prolonging drug is being evaluated. Among the adverse effects which cannot be anticipated are: hypersensitivity, ocular toxicity and CNS reactions.(ABSTRACT TRUNCATED AT 250 WORDS)