1. Introduction
TB, sepsis, Sepsis, human immunodeficiency virus (HIV)
SEPSIS, SEPSIS, DISEASES, TUBERCULOSIS (TB)
Sepsis is a significant cause of mortality among people living with human immunodeficiency virus (HIV) in sub-Saharan Africa. In the planning period prior to the start of a large multi-country clinical trial studying the efficacy of the immediate empiric addition of anti-tuberculosis therapy to standard-of-care antibiotics for sepsis in people living with HIV, we used decision analysis to assess the costs and potential health outcome impacts of the clinical trial design based on preliminary data and epidemiological parameter estimates. The purpose of this analysis was to highlight this approach as a case example where decision analysis can estimate the cost effectiveness of a proposed clinical trial design. In this case, we estimated the impact of immediate empiric anti-tuberculosis (TB) therapy versus the diagnosis-dependent standard of care using three different TB diagnostics: urine TB-LAM, sputum Xpert-MTB/RIF, and the combination of LAM/Xpert. We constructed decision analytic models comparing the two treatment strategies for each of the three diagnostic approaches. Immediate empiric-therapy demonstrated favorable cost-effectiveness compared with all three diagnosis-dependent standard of care models. In our methodological case exemplar, the proposed randomized clinical trial intervention demonstrated the most favorable outcome within this decision simulation framework. Applying the principles of decision analysis and economic evaluation can have significant impacts on study design and clinical trial planning. Clinical tuberculosis (TB) caused by the pathogen Microbiological culture for the detection of TB is the gold standard, but it is expensive and has a long wait time [Randomized control trials have become increasingly innovative and complex as adaptive designs, multi-center, and multi-country trials become the standard for many diseases including TB and sepsis [Decision analytic modeling is an analytic and simulation approach that integrates and synthesizes sources of evidence in the form of parameter estimates to calculate the cost-effectiveness of applying an intervention. In turn, this estimate can be used to anticipate the impact of the approach on a health system, payer, or society at large, and can be an integral component of clinical trial planning [The purpose of this analysis was to highlight this approach as a case example where decision analysis can estimate the cost effectiveness of a proposed clinical trial design and allow investigators and stakeholders to visualize the potential costs and health impacts based on prior knowledge of expected utilities. In this case, we estimated the impact of immediate empiric anti-TB therapy versus the diagnosis-dependent standard of care using three different TB diagnostics, urine TB-LAM (Alere Determine TB-LAM Ag, Abbot, Chicago, IL, USA) [