Trial designs for evaluating combination HIV prevention approaches

Chen, Ying Qing; Peng, Liang-You; Wang, Yixin; Appelmans, Eline; Dasgupta, Sayan; Fleming, Thomas R.

doi:10.1080/25787489.2020.1798083

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Integrated healthcare delivery models and ways to leverage community models of care could be examined during the study phase rather than only after the medications are approved. Factorial designs 54 could be leveraged to see which clinic supports are best positioned to enhance medication adherence, for example. Even open-label extension phases of protocols—which frequently are tacked onto Phase 3 studies after a medication is found to be effective—could be modified to have ancillary care services examined rigorously within the protocols for specified measurable outcomes.…”

Section: Provider and Clinic Characteristicsmentioning

confidence: 99%

Overcoming structural barriers to diffusion of HIV pre-exposure prophylaxis

Magnus,

Yellin,

Langlands

et al. 2023

The Journal of Medicine Access

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HIV prevention with antiretroviral medication in the form of pre-exposure prophylaxis (PrEP) offers a critical tool to halt the HIV pandemic. Barriers to PrEP access across drug types, formulations, and delivery systems share remarkable commonalities and are likely to be generalizable to future novel PrEP strategies. Appreciation of these barriers allows for planning earlier in the drug-development pathway rather than waiting for the demonstration of efficacy. The purpose of this article is to propose a core set of considerations that should be included in the drug-development process for future PrEP interventions. A literature synthesis of key barriers to PrEP uptake in the United States was conducted to elucidate commonalities across PrEP agents and delivery methods. Based on the published literature, we divided challenges into three main categories of structural barriers: (1) provider and clinic characteristics; (2) cost considerations; and (3) disparities and social constructs, with potential solutions provided for each. Pragmatic strategies for examining and overcoming these barriers before future PrEP regulatory approval are recommended. If these strategies are considered well before the time of commercial availability, the potential for PrEP to interrupt the HIV pandemic will be greatly enhanced.

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Section: Provider and Clinic Characteristicsmentioning

confidence: 99%

Overcoming structural barriers to diffusion of HIV pre-exposure prophylaxis

Magnus,

Yellin,

Langlands

et al. 2023

The Journal of Medicine Access

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Designing & Conducting Trials to Reliably Evaluate HIV Prevention Interventions

Fleming

DeGruttola

Donnell

2019

Statistical Communications in Infectious Diseases

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While much has been achieved, much remains to be accomplished in the science of preventing the spread of HIV infection. Clinical trials that are properly designed, conducted and analyzed are of integral importance in the pursuit of reliable insights about HIV prevention. As we build on previous scientific breakthroughs, there will be an increasing need for clinical trials to be designed to efficiently achieve insights without compromising their reliability and generalizability. Key design features should continue to include: (1) the use of randomization and evidence-based controls, (2) specifying the use of intention-to-treat analyses to preserve the integrity of randomization and to increase interpretability of results, (3) obtaining direct assessments of effects on clinical endpoints such as the risk of HIV infection, (4) using either superiority designs or non-inferiority designs with rigorous non-inferiority margins, and (5) enhancing generalizability through the choice of a relative risk rather than risk difference metric. When interventions have complementary and potentially synergistic effects, factorial designs should be considered to increase efficiency as well as to obtain clinically important insights about interaction and the contribution of component interventions to the efficacy and safety of combination regimens. Key trial conduct issues include timely enrollment of participants at high HIV risk recruited from populations with high viral burden, obtaining ‘best real-world achievable’ levels of adherence to the interventions being assessed and ensuring high levels of retention. High quality of trial conduct occurs through active rather than passive monitoring, using pre-specified targeted levels of performance with defined methods to achieve those targets. During trial conduct, active monitoring of the performance standards not only holds the trial leaders accountable but also can assist in the development and implementation of creative alternative approaches to increase the quality of trial conduct. Designing, conducting and analyzing HIV prevention trials with the quality needed to obtain reliable insights is an ethical as well as scientific imperative.

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Trial designs for evaluating combination HIV prevention approaches

Cited by 2 publications

References 25 publications

Overcoming structural barriers to diffusion of HIV pre-exposure prophylaxis

Overcoming structural barriers to diffusion of HIV pre-exposure prophylaxis

Designing & Conducting Trials to Reliably Evaluate HIV Prevention Interventions

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