Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D 2 EFT

作者：Emmanuelle Papot, Simone Jacoby, Dona Arlinda, Anchalee Avihingsanon, Iskandar Azwa, Margaret Borok, Dannae Brown, Mohamed Cissé, Sounkalo Dao, Nnakelu Eriobu, Richard Kaplan, Muhammad Karyana, Nagalingeswaran Kumarasamy, Johnnie Lee, Marcelo Losso, Gail Matthews, Leonardo Perelis, Carmen Pérez Casas, Kiat Ruxrungtham, Melynda Watkins, H. Clifford Lane, Anthony D. Kelleher, Matthew Law, Mark N. Polizzotto · 发表于：HIV Research & Clinical Practice · 年份：2022 · DOI：10.1080/25787489.2022.2103572 · 被引用次数：7 · 研究领域：Health Systems, Economic Evaluations, Quality of Life、Statistical Methods in Clinical Trials、Pharmaceutical Economics and Policy

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a...