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 diagnostics and strategies for treatment of co- infected patients lead to many clinical trial concepts, not all of which can be viably pursued. This proposal to NIAID will uniquely apply a mathematical simulation modeling framework, based on the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) Model, to the NIAID/ACTG clinical trials infrastructure. We propose to inform the development, design, and assessment of therapeutic, diagnostic, and 'strategy'clinical trials in HIV/TB care in international settings with 3 focused specific aims: 1) To use microsimulation methods to determine the value of information of specific clinical trials, balancing the projected clinical and economic costs of uncertainty with the overall resources necessary to obtain trial-quality evidence. 2) To utilize model-based pre-trial evaluation methods to inform multiple aspects of HIV/TB trial design, including specification of alternative strategies, estimation of clinically meaningful outcomes, and establishment of targets for statistical standards of evidence. 3) To utilize short-term outcomes obtained from recently completed trials in order to project clinical and economic results beyond the boundaries imposed by trial limitations, including longer time horizons, alternative patient populations, as well as clinical and policy application to countries beyond the clinical trial sites. The ultimate goal of this proposal from Dr. Rochelle Walensky -- Principal Investigator and accomplished CEPAC investigator -- is to apply novel scientific methods in a highly innovative fashion, to maximize trial investments. It will develop new scientific knowledge of value to HIV/TB investigators, as well as clinical trialists in many areas of medicine. Relevance In this difficult economy, HIV, tuberculosis, and their co-infection remain among the largest challenges to global health. Given that research funding availability prohibits the pursuit of answers to all questions through gold-standard clinical trials, this proposal will use novel microsimulation methods to evaluate trials under development for efficiency and to optimize the value of trials that are ultimately conducted.

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. In collaboration with the Adult AIDS Clinical Trial Group (ACTG), we propose to use the CEPAC-International Model - a microsimulation model of HIV/TB disease, populated with data from resource-limited settings - to add unique added value to HIV/TB clinical trial development. The proposed microsimulation analyses will offer a comparatively rapid and efficient way to evaluate clinical trials that are worth doing and likely to have a policy impact.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI093269-03
Application #
8519284
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
Project Start
2011-09-01
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$545,328
Indirect Cost
$155,683
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Hermans, Sabine; Caldwell, Judy; Kaplan, Richard et al. (2017) The impact of the roll-out of rapid molecular diagnostic testing for tuberculosis on empirical treatment in Cape Town, South Africa. Bull World Health Organ 95:554-563
Bassett, Ingrid V; Coleman, Sharon M; Giddy, Janet et al. (2017) Barriers to Care and 1-Year Mortality Among Newly Diagnosed HIV-Infected People in Durban, South Africa. J Acquir Immune Defic Syndr 74:432-438
Bassett, Ingrid V; Coleman, Sharon M; Giddy, Janet et al. (2016) Sizanani: A Randomized Trial of Health System Navigators to Improve Linkage to HIV and TB Care in South Africa. J Acquir Immune Defic Syndr 73:154-60
Girouard, Michael P; Sax, Paul E; Parker, Robert A et al. (2016) The Cost-effectiveness and Budget Impact of 2-Drug Dolutegravir-Lamivudine Regimens for the Treatment of HIV Infection in the United States. Clin Infect Dis 62:784-91
Walensky, Rochelle P; Jacobsen, Margo M; Bekker, Linda-Gail et al. (2016) Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection. J Infect Dis 213:1523-31
Jacobsen, Margo M; Walensky, Rochelle P (2016) Modeling and Cost-Effectiveness in HIV Prevention. Curr HIV/AIDS Rep 13:64-75
Kaplan, R; Caldwell, J; Hermans, S et al. (2016) An integrated community TB-HIV adherence model provides an alternative to DOT for tuberculosis patients in Cape Town. Int J Tuberc Lung Dis 20:1185-91
Blaser, Nello; Zahnd, Cindy; Hermans, Sabine et al. (2016) Tuberculosis in Cape Town: An age-structured transmission model. Epidemics 14:54-61
Freedberg, Kenneth A; Possas, Cristina; Deeks, Steven et al. (2015) The HIV Cure Research Agenda: The Role of Mathematical Modelling and Cost-Effectiveness Analysis. J Virus Erad 1:245-249
Ciaranello, Andrea L; Doherty, Kathleen; Penazzato, Martina et al. (2015) Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African children less than 3 years of age. AIDS 29:1247-59

Showing the most recent 10 out of 39 publications