DEALING WITH ADVERSE EVENTS IN PHASE-I TR IALS

A questionnaire was completed by members of the Association for Applie d Human Pharmacology (AGAH) in Germany with the aim of assessing the p resent situation regarding management of adverse events (AEs). A recom mendation for documentation and evaluation of AEs was to be presented after discussion within the AGAH. The questionnaire referred to genera l questions, documentation of AEs, intensity and causality, coding and serious adverse events (SAE). Percentage return of answered questionn aires was 54.5%. Of the people contacted, 9.1% said they did not carry out phase I trials, and 36.4% did not reply. The survey in the 24 ins titutes convers an estimated 11200 volunteers who are included in clin ical trials each year. The discussion about commencement of AEs docume ntation and its duration was contentious. Of the respondents, 38.5% AE s only after application of the trial substance, while 61.5% also make a documentation during the pre-trial phase (recruitment, pre-examinat ion, supervision before application). 13.6% document only up to the po st-examination and half of those questioned until AE symptoms have dis appeared. 22.7% document until disappearance of symptoms only when AEs are definitely associated with the trial substance. A 3-point scale i s used by most people questioned for evaluation of the intensity of an AE. Evaluation of causality, mostly undertaken by the examining physi cian and the director of the clinical trial, is not carried out homoge neously. There are several categories, but four classifications are mo st commonly used. 62.5% of codings of AEs are carried out according to the WHO Adverse Reaction Terminology. 12.5% of those questioned used Costart, HARTS, as well as internal systems for coding. AEs manifested in altered laboratory and vital parameters are mostly documented by a nalyses beyond the normal range of values. There was widespread agreem ent regarding management of SAEs relative to emergency equipment and c are. After evaluation of different documentation report forms which se rved as examples, the fundamental content of a documentation report fo rm will be suggested.