During the first 3.5 years of this R37 cycle, Novel Methods to Inform HIV/TB Clinical Trial Development has used decision science methodologies, focusing on value of information, and demonstrated outstanding productivity, methods expansion, trainee development, policy impact, and international collaboration. As we complete this cycle and look forward to the subsequent one, we will continue to develop and utilize novel VOI methods, applying them to ongoing and new international trial activities with the following specific aims: 1) To calculate the expected value of sample information (ESVI) using generalized additive models (GAMs) within the Monte Carlo simulation of the Cost-effectiveness of Preventing AIDS Complications (CEPAC) model. 2) To expand upon the methods developed in Aim 1 to inform new clinical trial design, post-trial evaluation, and priority setting in the areas of HIV and TB in South Africa, focusing on newly reported and potential high-impact trials. We will focus on three areas: i. Antiretroviral Treatment Strategies ii. Vaccines and Antibody-Mediated Prevention iii. Novel Tuberculosis Diagnostic, Treatment, and Vaccination Strategies We anticipate continued major productivity in the next R37 cycle, informing decision makers on efficient use of resources both in the implementation of trial results once already performed and in the conduct of those being designed. RELEVANCE (See instructions): HIV and TB remain high among the top ten causes of death in low-income countries. Given the budgetary constraints to conduct the array of ongoing and potential clinical trials, we have developed a Value of Information (VOI) framework to assess a priori which trials might provide the best value, formally comparing courses of action with and without new information – as might be obtained from a trial – to quantify the value of information acquisition, accounting for both the trial benefits and costs.