Ethical and Legal Considerations for Realising Post-trial Access of Novel Experimental Interventions: Lessons from the CAPRISA 004 Trial

Abstract

The CAPRISA 004 trial, a phase 2b, double-blind, randomised, placebo-controlled trial, revolutionised the HIV prevention arena, particularly the microbicide field, by becoming the first study to demonstrate efficacy of a HIV microbicide product. The trial found that 1% tenofovir gel was 39 % efficacious in preventing vaginal HIV infection, and 51% efficacious in preventing herpes simplex virus type 2 (HSV-2) amongst women [1]. The study also found that women who adhered to the prescribed regimen of two doses of tenofovir gel for more than 80% of their sex acts had a 54% lower risk of HIV infection. Despite the trial’s success, as the CAPRISA 004 trial was a phase 2b trial, drug regulatory authorities—such as the United States Federal Drug Administration (FDA) and South Africa’s Medicine Control Council (MCC)—required additional confirmatory evidence from a phase 3 trial before registering and license the product as a HIV prevention agent for females. In the aftermath of the CAPRISA 004 trial, even if a follow-up phase 3 confirmatory trial yielded evidence in support of the CAPRISA 004 trial’s findings, it was realistic to expect that tenofovir gel would only obtain licensure 4–5 years after the conclusion of the CAPRISA 004 trial. Such a delay raised profound ethical, legal and human rights issues regarding CAPRISA 004 trial participants’ access to tenofovir gel during the period between the conclusion of the CAPRISA 004 trial and the results of the follow-up phase 3 confirmatory trial (the FACTS-001 trial [2]), and moreover, between the conclusion of the CAPRISA 004 trial and its potential licensure by regulatory authorities. How CAPRISA considered and realised its post-trial obligations towards relevant participants of the CAPRISA 004 trial may be instructive to others facing similar dilemmas.