# Statistical methods for clinical trials of novel PrEP agents

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $121,125

## Abstract

PROJECT SUMMARY
HIV pre-exposure prophylaxis (PrEP) with co-formulated emtricitabine tenofovir (TDF/FTC) in HIV negative
persons is safe and effective for preventing HIV infection. Despite notable successes, PrEP has important
limitations as a broad prevention tool. Some people who would benefit from PrEP refuse it or are poorly
adherent. Surveys indicate that many of those at risk for HIV believe that daily oral TDF/FTC to be difficult to
adhere to or unappealing and would be prefer a non-oral alternative. This has also been shown to be true in
contraception. To maximize the benefits of biomedical prevention, we need alternatives to oral TDF/FTC.
There is a robust pipeline of novel PrEP methods (NPM) in development. There are antiretrovirals formulated
as injectables, infusions, implantables and microbicides. Some of these have entered phase III randomized
trials and others could enter trials over the next 2-4 years. Since PrEP has shown effectiveness, the trials must
make some provision for it ethically. For injections and implants, TDF/FTC will likely be a comparator arm and
the degree of TDF/FTC adherence in these future studies is very uncertain – greatly complicating the
comparison of the two arms. Standard methods lead to long expensive studies which will slow PrEP
innovation.
We believe can significantly increase power and/or lower the cost of future active-controlled randomized trials.
By innovatively using post-baseline TDF/FTC pharmacology, which is well-studied in previous trials, to
reconstruct a counterfactual placebo arm. This permits comparisons of the novel PrEP method to putative
placebo in both intent to treat (ITT) and as-treated (AT) analyses – gaining substantial insight and statistical
efficiency. We will also develop models and methods to understand who will sustain engagement with a NPM
but not oral PrEP. By leveraging the well-studied TDF/FTC pharmacology and modern causal inference
methods, we will to develop analysis methods and non-inferiority frameworks that allow next generation PrEP
trials to be smaller, quicker and more informative.

## Key facts

- **NIH application ID:** 9984288
- **Project number:** 5R01AI143357-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DAVID V. GLIDDEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $121,125
- **Award type:** 5
- **Project period:** 2018-09-24 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984288

## Citation

> US National Institutes of Health, RePORTER application 9984288, Statistical methods for clinical trials of novel PrEP agents (5R01AI143357-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9984288. Licensed CC0.

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