  In the realm of medical research, the intricate interplay of epidemiological
risk, genomic activity, adverse events, and clinical response necessitates a
nuanced consideration of multiple variables. Clinical trials, designed to
meticulously assess the efficacy and safety of interventions, routinely
incorporate a diverse array of endpoints. While a primary endpoint is
customary, supplemented by key secondary endpoints, the statistical
significance is typically evaluated independently for each. To address the
inherent challenges in studying multiple endpoints, diverse strategies,
including composite endpoints and global testing, have been proposed. This work
stands apart by focusing on the evaluation of a clinical trial, deviating from
the conventional approach to underscore the efficacy of a multiple-endpoint
procedure. A double-blind study was conducted to gauge the treatment efficacy
in adults infected with human immunodeficiency virus type 1 (HIV-1), featuring
CD4 cell counts ranging from 200 to 500 per cubic millimeter. A total of 2467
HIV-1-infected patients (43 percent without prior antiretroviral treatment)
were randomly assigned to one of four daily regimens: 600 mg of zidovudine; 600
mg of zidovudine plus 400 mg of didanosine; 600 mg of zidovudine plus 2.25 mg
of zalcitabine; or 400 mg of didanosine. The primary endpoint comprised a >50
percent decline in CD4 cell count, development of acquired immunodeficiency
syndrome (AIDS), or death. This study sought to determine the efficacy and
safety of zidovudine (AZT) versus didanosine (ddI), AZT plus ddI, and AZT plus
zalcitabine (ddC) in preventing disease progression in HIV-infected patients
with CD4 counts of 200-500 cells/mm3. By jointly considering all endpoints, the
multiple-endpoints approach yields results of greater significance than a
single-endpoint approach.
