Document 0301
 DOCN  M9550301
 TI    Considerations in choice of a clinical endpoint for AIDS clinical
       trials. Terry Beirn Community Programs for Clinical Research on AIDS
       (CPCRA).
 DT    9505
 AU    Neaton JD; Wentworth DN; Rhame F; Hogan C; Abrams DI; Deyton L; Division
       of Biostatistics, School of Public Health, University of; Minnesota,
       Minneapolis 55414.
 SO    Stat Med. 1994 Oct 15-30;13(19-20):2107-25. Unique Identifier : AIDSLINE
       MED/95149006
 AB    In most clinical trials of antiretroviral therapy for patients infected
       with HIV, the major outcome variable has been the combined clinical
       endpoint of any new or recurrent AIDS defining event. We review features
       of combined endpoints and use data from the Terry Beirn Community
       Programs for Clinical Research on AIDS (CPCRA) to evaluate this outcome
       measure in terms of relevance, diagnostic certainty and sensitivity. We
       conclude that this endpoint is not relevant because: (i) the 19
       different events constituting the combined endpoint are equally weighted
       in analyses even though they vary considerably in terms of risk of
       death; and (ii) events after the first are ignored, thus the event
       profile of patients is not taken into account in making treatment
       comparisons. We also conclude that power may be low with use of this
       endpoint if treatments under study do not have an immediate impact on
       disease progression, if some events which occur soon after randomization
       represent a disease process that has already begun to incubate, or if
       treatment differences for the various events constituting the combined
       endpoint are differentially effected by treatment. Since the ease and
       certainty of diagnosis of each of the 19 events also vary, we recommend
       that survival be the primary endpoint of antiretroviral trials, and that
       all opportunistic events experienced by patients, not just the first, be
       collected and summarized. Trial reports should include comparisons of
       incidence of each event by treatment group so that readers can rank
       events as they please. A single summary measure which considers severity
       and the entire event profile, as described here, would also be useful
       for assessing the impact of treatments on quality of life. Further
       research on approaches for weighting and combining multiple outcome
       measures is needed.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/EPIDEMIOLOGY
       AIDS-Related Opportunistic Infections  Clinical Trials/*STATISTICS &
       NUMER DATA  *Data Interpretation, Statistical  Disease Progression
       Human  *Models, Statistical  Survival Analysis  Treatment Outcome
       JOURNAL ARTICLE  REVIEW  REVIEW LITERATURE

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