[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)]. / Erfassung und Anzeige von Nebenwirkungen in klinischen Prüfungen Neue gesetzliche Bestimmungen in der 12. AMG-Novelle und der GCP-Verordnung.

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

[Documentation and assessment of adverse drug effects with ofloxacin as an example]. / Dokumentation und Bewertung von Arzneimittelnebenwirkungen am Beispiel des Ofloxacins.

A systematical and comprehensive evaluation of all reports on adverse drug reactions ascribed to ofloxacin since this antibiotic was launched (1985) until October 1988 shows that rare and severe adverse drug reactions are more often reported spontaneously than in the course of clinical trials. In particular, severe reductions of white blood cell counts, shock and shock fragments, and impairment of sensory organs and renal functions have for the first time been detected by spontaneous case reports. The results demonstrate exemplarily the potency of the spontaneous reporting system as superior to that of clinical trials in providing information on rare adverse drug reactions.