Considerations in choosing a primary endpoint that measures durability of virological suppression in an antiretroviral trial

Abstract

A time from randomization endpoint is usually recommended because of its advantages in flexibility and sample size, especially at interim analyses, and for its interpretation for patient management.

Methodological issues in the use of composite endpoints in clinical trials: examples from the HIV field

“…They found that both the choice of definition of the early failure time and the assigned failure time in this time-to-event endpoint definition influenced the results. The authors concluded that a time-from-randomization endpoint should be used that assigns subjects with early virological failure within T weeks a failure time of T weeks (where T is chosen such that >95% of responders are expected to respond by time T) [37].…”

Viral suppression in HIV studies: Combining times to suppression and rebound

“…Gilbert et al, (2000) expand on the discussion of virologic failure and consider several competing definitions. Ribaudo et al (2006) discussed design issues in HIV trials, concentrating the discussion of endpoints on further refinements in virologic failure.…”

“…However, in some settings a clear definition of the event of interest is a challenge. An example of such settings include clinical trials evaluating the difference between treatments which are intended to suppress the level of HIV-1 RNA viral load (henceforth viral load) in people infected with HIV (DeGruttola et al, 1998; Gilbert et al, 2000; Ribaudo et al, 2006). …”

Illustration of a Measure to Combine Viral Suppression and Viral Rebound in Studies of HIV Therapy

“…Perhaps the most commonly used endpoint to compare the efficacy of treatment plans is the time to “virologic failure” 3–7 . The time to virologic failure for patients whose viral load is not suppressed by a predetermined time during the study period is often set to that predetermined time 5,6 or time zero 8 .…”