2019/06/19 by Peter B. Gilbert, Gilbert, Peter B.
Immunology and Microbiology · Mathematics · #HIV Research and Treatment #Statistical Methods in Clinical Trials #Advanced Causal Inference Techniques
paper · pdf · doi:10.48550/arxiv.1906.08409
Four randomized placebo-controlled efficacy trials of a candidate vaccine or\npassively infused monoclonal antibody for prevention of HIV-1 infection are\nunderway (HVTN 702 in South African men and women; HVTN 705 in sub-Saharan\nAfrican women; HVTN 703/HPTN 081 in sub-Saharan African women; HVTN 704/HPTN\n085 in U.S., Peruvian, Brazilian, and Swiss men or transgender persons who have\nsex with men). Several challenges are posed to the optimal design of the sequel\nefficacy trials, including: (1) how to account for the evolving mosaic of\neffective prevention interventions that may be part of the trial design or\nstandard of prevention; (2) how to define viable and optimal sequel trial\ndesigns depending on the primary efficacy results and secondary 'correlates of\nprotection' results of each of the ongoing trials; and (3) how to define the\nprimary objective of sequel efficacy trials if HIV-1 incidence is expected to\nbe very low in all study arms such that a standard trial design has a steep\nopportunity cost. After summarizing the ongoing trials, I discuss statistical\nscience considerations for sequel efficacy trial designs, both generally and\nspecifically to each trial listed above. One conclusion is that the results of\n'correlates of protection' analyses, which ascertain how different host\nimmunological markers and HIV-1 viral features impact HIV-1 risk and prevention\nefficacy, have an important influence on sequel trial design. This influence is\nespecially relevant for the monoclonal antibody trials because of the focused\npre-trial hypothesis that potency and coverage of serum neutralization\nconstitutes a surrogate endpoint for HIV-1 infection... (see manuscript for the\nfull abstract)\n