EXPERIENCE WITH A CROSS-STUDY END-POINT REVIEW COMMITTEE FOR AIDS CLINICAL-TRIALS

Objectives: To describe the methods and results of a standardized syst em for clinical endpoint determination for defining and reviewing endp oints in clinical trials for HIV-infected individuals. Design: A syste m was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease'. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carnii pneumonia (PCP), for example, for a subject co-enrolled in an a ntiretroviral trial and a PCP prophylaxis trial was only reported once . Methods: A central committee was established to define clinical even ts and review endpoints across all studies. Events were classified acc ording to established criteria for confirmed, probable and possible le vels of certainty. Results: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events fo r 8097 subjects enrolled in one or more of nine clinical trials. Data an the diagnostic certainty of events and agreement between site clini cians and the endpoint committee are presented. Conclusions: Uniform c lassification of endpoints across AIDS clinical trials can be accompli shed by multicenter, multitrial organizations with standardized defini tions and review of endpoint documentation. Our experience suggests th at nurse coordinators reviewing all submitted endpoints for every tria l are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted. (C) 1998 Lippinco tt Williams & Wilkins.