Mosaic effectiveness: measuring the impact of novel PrEP methods

Abstract

Summary: A number of ongoing trials seek to evaluate long-acting PrEP agents in by demonstrating it is non-inferior to daily oral TDF/FTC. A trial comparing oral PrEP to a new method compares effectiveness in a setting where only one or the other is provided; however, a new product will likely be delivered in a context where oral PrEP is also available. Its impact is best measured by its potential contribution in a context that also includes oral TDF/FTC as an option. Will it extend the reach of effective biomedical HIV prevention? We offer an alternative standard for long-acting products—a measure of the effectiveness of the new product in addition to oral TDF/FTC as compared to oral TDF/FTC alone. We term this quantity “mosaic effectiveness”—a compelling measure of impact. We illustrate scenarios where a novel product can fail the to show non-inferiority but demonstrates substantial mosaic effectiveness, thus implying the public health utility of the novel product even if it is less effective than oral PrEP. Regulatory standards should take into account mosaic effectiveness not just comparative effectiveness. Thus, standards for products that combine rigor with public health relevance can accelerate progress against the HIV epidemic.

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study

“…Additional statistical and operational approaches have been proposed and will need to be explored for future trials. 11,[25][26][27] The ethical conduct of research mandates access to effective prevention, which includes PrEP. Ease of access to tenofovir disoproxil fumarate and emtricitabine PrEP has sometimes been a logistical challenge in trials, presenting a substantial barrier to actual use of PrEP.…”

“…Additional statistical and operational approaches have been proposed and will need to be explored for future trials. 11 , 25 , 26 , 27 …”

Future directions for HIV service delivery research: Research gaps identified through WHO guideline development

“…Given the range of differentiated service delivery models being considered by national HIV treatment programs (e.g., community- and facility-based adherence clubs), the guideline development group considered that research on the comparative effectiveness, comparative cost-effectiveness, and comparative implementability of these models would be important to inform policy and prioritization. The introduction of one model to existing models would be useful to understand the additional contribution of a program to “mosaic effectiveness” [ 21 ].…”

A Bayesian averted infection framework for PrEP trials with low numbers of HIV infections: application to the results of the DISCOVER trial

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There is an urgent need for innovative trial approaches which can ethically and rigorously assess new HIV prevention methods. [1][2][3][4] Randomized active controlled trials, with an oral emtricitabine plus tenofovir disoproxil fumarate (F/TDF) control group, have been the preferred design for assessing new pre-exposure prophylaxis (nPrEP) agents. To date, active controlled nPrEP trials have been large and expensive, with power calculations requiring observation of at least 100 incident HIV infections.

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