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

Alan R. Lifson, 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

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalHIV Clinical Trials
Volume9
Issue number3
DOIs
StatePublished - May 2008

Keywords

  • Cause of death
  • Clinical trials
  • Endpoint review committees
  • HIV
  • Mortality

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