Determination of the underlying cause of death in three multicenter international HIV clinical trials - PubMed (original) (raw)

. 2008 May-Jun;9(3):177-85.

doi: 10.1310/hct0903-177.

INSIGHT Cause of Death Writing Group; Waldo H Belloso, Cate Carey, Richard T Davey, Daniel Duprez, Wafaa M El-Sadr, Jose M Gatell, Daniela C Gey, Jennifer F Hoy, Eric A Krum, Ray Nelson, Daniel E Nixon, Nick Paton, Court Pedersen, George Perez, Richard W Price, Ronald J Prineas, Frank S Rhame, James Sampson, John Worley

Collaborators, Affiliations

Determination of the underlying cause of death in three multicenter international HIV clinical trials

Alan R Lifson et al. HIV Clin Trials. 2008 May-Jun.

Abstract

Purpose: Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials.

Method: Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36 countries during 1999-2008. Three ERC members independently reviewed each death report and supporting source documentation to assign underlying cause of death; differences of opinion were adjudicated.

Results: Of 453 deaths reported through January 14, 2008, underlying causes were as follows: 10% AIDS-defining diseases, 21% non-AIDS malignancies, 9% cardiac diseases, 9% liver disease, 8% non-AIDS-defining infections, 5% suicides, 5% other traumatic events/accidents, 4% drug overdoses/acute intoxications, 11% other causes, and 18% unknown. Major reasons for unknown classification were inadequate clinical information or supporting documentation to determine cause of death. Half (51%) of deaths reviewed by the ERC required follow-up adjudication; consensus was eventually always reached.

Conclusion: ERCs can successfully provide blinded, independent, and systematic determinations of underlying cause of death in HIV clinical trials. Committees should include those familiar with AIDS and non-AIDS-defining diseases and have processes for adjudicating differences of opinion. Training for local investigators and procedure manuals should emphasize obtaining maximum possible documentation and follow-up information on all trial deaths.

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