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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
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Massachusetts General Hospital
United States
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