Counterfactual Controls for HIV Prevention Trials

• Activity Number: 365 - Causal Integration of Randomized Clinical Trials and Real-World Data: Challenges and Opportunities
• Type: Invited
• Date/Time: Wednesday, August 10, 2022 : 8:30 AM to 10:20 AM
• Sponsor: WNAR
• Author(s): Deborah Donnell* and Fei Gao
• Companies: Fred Hutchinson Cancer Research Center and Fred Hutchinson Cancer Research Center
• Keywords: clinical trials; counterfactual; HIV prevention; PrEP; placebo

Abstract

Clinical trials of new antiretroviral-based agents for pre-exposure prophylaxis (PrEP) for HIV prevention are becoming increasingly difficult, as there is now proven biomedical prevention with > 90% efficacy. It is not ethical to include a placebo-only group and HIV infections rates are expected to be very low (< 0.5/100 person years) when trial participants are randomized to use existing prevention drugs. Innovative ways to evaluate the placebo-based efficacy of new PrEP modalities are needed given that sample sizes in at-risk persons, required for traditional non-inferiority trials, are not feasible. Approaches to develop valid, robust counterfactual placebo estimates of HIV incidence may offer a pathway to approval of new PrEP drugs tested in clinical trials. In this talk I will discuss the statistical challenges of several new strategies that have been proposed. These include the use of HIV recent infection testing algorithms (RITAs) in untreated, HIV-positive people identified during screening, and bridging placebo data on HIV infection rates from external trials.