The Value-of-Information and Value-of-Implementation from Clinical Trials of Diagnostic Tests for HIV-Associated Tuberculosis: A Modeling Analysis

Objectives. Conventional value-of-information (VOI) analysis assumes complete uptake of an optimal decision. We employed an extended framework that includes value-of-implementation (VOM)—the benefit of encouraging adoption of an optimal strategy—and estimated how future trials of diagnostic tests for HIV-associated tuberculosis could improve public health decision making and clinical and economic outcomes. Methods. We evaluated the clinical outcomes and costs, given current information, of 3 tuberculosis screening strategies among hospitalized people with HIV in South Africa: sputum Xpert (Xpert), sputum Xpert plus urine AlereLAM (Xpert+AlereLAM), and sputum Xpert plus the newer, more sensitive, and costlier urine FujiLAM (Xpert+FujiLAM). We projected the incremental net monetary benefit (INMB) of decision making based on results of a trial comparing mortality with each strategy, rather than decision making based solely on current knowledge of FujiLAM’s improved diagnostic performance. We used a validated microsimulation to estimate VOI (the INMB of reducing parameter uncertainty before decision making) and VOM (the INMB of encouraging adoption of an optimal strategy). Results. With current information, adopting Xpert+FujiLAM yields 0.4 additional life-years/person compared with current practices (assumed 50% Xpert and 50% Xpert+AlereLAM). While the decision to adopt this optimal strategy is unaffected by information from the clinical trial (VOI = $ 0 at $3,000/year-of-life saved willingness-to-pay threshold), there is value in scaling up implementation of Xpert+FujiLAM, which results in an INMB (representing VOM) of $650 million over 5 y. Conclusions. Conventional VOI methods account for the value of switching to a new optimal strategy based on trial data but fail to account for the persuasive value of trials in increasing uptake of the optimal strategy. Evaluation of trials should include a focus on their value in reducing barriers to implementation. HIGHLIGHTS: In conventional VOI analysis, it is assumed that the optimal decision will always be adopted even without a trial. This can potentially lead to an underestimation of the value of trials when adoption requires new clinical trial evidence. To capture the influence that a trial may have on decision makers’ willingness to adopt the optimal decision, we also consider value-of-implementation (VOM), a metric quantifying the benefit of new study information in promoting wider adoption of the optimal strategy. The overall value-of-a-trial (VOT) includes both VOI and VOM. Our model-based analysis suggests that the information obtained from a trial of screening strategies for HIV-associated tuberculosis in South Africa would have no value, when measured using traditional methods of VOI assessment. A novel strategy, which includes the urine FujiLAM test, is optimal from a health economic standpoint but is underutilized. A trial would reduce uncertainties around downstream health outcomes but likely would not change the optimal decision. The high VOT (nearly $700 million over 5 y) lies solely in promoting uptake of FujiLAM, represented as VOM. Our results highlight the importance of employing a more comprehensive approach for evaluating prospective trials, as conventional VOI methods can vastly underestimate their value. Trialists and funders can and should assess the VOT metric instead when considering trial designs and costs. If VOI is low, the VOM and cost of a trial can be compared with the benefits and costs of other outreach programs to determine the most cost-effective way to improve uptake.