Clinical trials provide the highest standard of evidence for HIV/TB co-infected patients, but they utilize substantial resources in terms of personnel, subjects, time, and cost. Ongoing research questions regarding both diagnosis and management of co-infected patients lead to many clinical trial concepts, not all of which can viably be pursued. This renewal application to NIAID will uniquely apply a mathematical simulation modeling framework, based on the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) Model, to the NIAID clinical trials infrastructure. In the first 3 years of the initial award, we have used these novel methods to publish 17 papers (and 2 editorials) related to the conduct, design, and value of HIV/TB-related clinical trials, including one in The New England Journal of Medicine. We now propose 2 new specific aims: 1) To develop and advance the practical use of methods for Value of Information (VOI) analysis, particularly to estimate the Expected Value of Sample Information (EVSI) of potential clinical trials. EVSI offers insight into whether further trial-based research is beneficial; into the extent of that benefit gien current pre-trial information; and into the most efficient trial size and design. We will streamlin computational approaches and assess the marginal benefits and costs of changes associated with alternative trial sample sizes. 2) To inform clinical trial design and priority setting in th area of HIV/TB by conducting a series of policy evaluations that leverage the analytic advances developed in the prior cycle and in Aim 1. Long-acting pre-exposure prophylaxis (LA-PrEP). We will examine the value of mounting an LA- PrEP trial in resource-limited settings, taking into account both the projected incremental efficacy benefit, as well as the drug and management costs of LA-PrEP. *Tuberculosis diagnostics. We will assess the value of a clinical trial of novel TB diagnostics at the time of HIV diagnosis in TB endemic areas. We will account for uncertainty in empiric TB therapy rates and examine the incremental benefit of larger trial sample sizes given increased trial costs. HIV cure. We will examine critical benchmarks for the viability of a trial of alternative HIV cure strategies in resource-limited settings. These benchmarks include: population eligibility, intervention efficacy and toxicity, relapse and re-infection rates, quality of life benefits, and costs. The ultimate goal of this proposal is to help decision makers choose the best possible use of scarce clinical trial resources by developing and disseminating novel methods to understand the value of information of proposed HIV/TB-related trials over the next decade.

Public Health Relevance

The global HIV/TB pandemic has resulted in a breadth of research questions, not all of which may be affordably addressed using the gold-standard clinical trial research design. We propose to apply innovative modeling approaches to the CEPAC-International Model - a microsimulation model of HIV/TB disease, populated with data from resource-limited settings - to add unique value to HIV/TB clinical trial development. We will apply these rapid, efficient, and novel methods to help prioritize HIV/TB clinical trials among those that will provide the most value and have the greatest policy impact.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI093269-07
Application #
9336787
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
Project Start
2011-09-01
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
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Luz, Paula M; Osher, Benjamin; Grinsztejn, Beatriz et al. (2018) The cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil. J Int AIDS Soc 21:e25096
Neilan, Anne M; Cohn, Jennifer E; Lemaire, Jean-Francois et al. (2018) HIV Testing After a First Positive Rapid Diagnostic Test: A Role for Nucleic Acid Testing? Open Forum Infect Dis 5:ofy170
Freedberg, Kenneth A; Kumarasamy, Nagalingeswaran; Borre, Ethan D et al. (2018) Clinical Benefits and Cost-Effectiveness of Laboratory Monitoring Strategies to Guide Antiretroviral Treatment Switching in India. AIDS Res Hum Retroviruses 34:486-497
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Zheng, Amy; Kumarasamy, Nagalingeswaran; Huang, Mingshu et al. (2018) The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India. J Int AIDS Soc 21:e25085
Rabideau, Dustin J; Pei, Pamela P; Walensky, Rochelle P et al. (2018) Implementing Generalized Additive Models to Estimate the Expected Value of Sample Information in a Microsimulation Model: Results of Three Case Studies. Med Decis Making 38:189-199
Borre, Ethan D; Hyle, Emily P; Paltiel, A David et al. (2017) The Clinical and Economic Impact of Attaining National HIV/AIDS Strategy Treatment Targets in the United States. J Infect Dis 216:798-807
Walensky, Rochelle P; Borre, Ethan D; Bekker, Linda-Gail et al. (2017) Do Less Harm: Evaluating HIV Programmatic Alternatives in Response to Cutbacks in Foreign Aid. Ann Intern Med 167:618-629

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