Data Monitoring in the AIDS Clinical Trials Group Study #981: Conflicting Interim Results

Abstract

In 1989, the NIH sponsored AIDS Clinical Trials Group (ACTG) mounted a large prospective randomized trial (known as ACTG 981) to compare fluconazole (200 mg daily) with clotrimazole lozenges (10mg, five times daily) for prevention of invasive fungal infections in patients with advanced HIV disease. At the fourth DSMB review of the study in November 1992, the patients on fluconazole had a significantly lower risk of invasive, serious and superficial fungal infections, but a higher mortality rate than the patients on clotrimazole. The DSMB recommended keeping the study open in spite of the fact that a boundary had been crossed for the primary endpoint. The final analysis of this study, published in the New England Journal of Medicine, reported that the trial gave evidence of the superiority of fluconazole in preventing the most serious fungal infections, but did not show an advantage in reducing overall mortality, thus vindicating the recommendations of the DSMB to keep the trial open until the planned follow-up had been completed. This paper is a review of the DSMB process for this study, and how the Board dealt with the challenges of interpretation of apparently contradictory evidence on treatment efficacy.