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Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis.

ABSTRACT: Background: Active case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting?

Methods and findings: We constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) 'moderate accuracy' testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) 'high accuracy' testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75-1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions.

Conclusions: Our results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.

SUBMITTER: Cilloni L

PROVIDER: S-EPMC7710036 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis.

Cilloni Lucia L Kranzer Katharina K Stagg Helen R HR Arinaminpathy Nimalan N

PLoS medicine 20201202 12

<h4>Background</h4>Active case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting?<h4>Methods and findings</h4>We constructed a dynamic transmissi ...[more]

PMID: 33264288

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Project description:BackgroundIn the last decade, active case finding (ACF) strategies for tuberculosis (TB) have been implemented in many diverse settings, with some showing large increases in case detection and reporting at the sub-national level. There have also been several studies which seek to provide evidence for the benefits of ACF to individuals and communities in the broader context. However, there remains no quantification of the impact of ACF with regards to reducing the burden of transmission. We sought to address this knowledge gap and quantify the potential impact of active case finding on reducing transmission of TB at the national scale and further, to determine the intensification of intervention efforts required to bring the reproduction number (R0) below 1 for TB.MethodsWe adopt a dynamic transmission model that incorporates heterogeneity in risk to TB to assess the impact of an ACF programme (IMPACT TB) on reducing TB incidence in Vietnam and Nepal. We fit the models to country-level incidence data using a Bayesian Markov Chain Monte Carlo approach. We assess the impact of ACF using a parameter in our model, which we term the treatment success rate. Using programmatic data, we estimate how much this parameter has increased as a result of IMPACT TB in the implementation districts of Vietnam and Nepal and quantify additional efforts needed to eliminate transmission of TB in these countries by 2035.ResultsExtending the IMPACT TB programme to national coverage would lead to moderate decreases in TB incidence and would not be enough to interrupt transmission by 2035. Decreasing transmission sufficiently to bring the reproduction number (R0) below 1, would require a further intensification of current efforts, even at the sub-national level.ConclusionsActive case finding programmes are effective in reducing TB in the short term. However, interruption of transmission in high-burden countries, like Vietnam and Nepal, will require comprehensive incremental efforts. Complementary measures to reduce progression from infection to disease, and reactivation of latent infection, are needed to meet the WHO End TB incidence targets.

Project description:Value-based decision-making involves trading off the cost associated with an action against its expected reward. Research has shown that both physical and mental effort constitute such subjective costs, biasing choices away from effortful actions, and discounting the value of obtained rewards. Facing conflicts between competing action alternatives is considered aversive, as recruiting cognitive control to overcome conflict is effortful. Moreover, engaging control to proactively suppress irrelevant information that could conflict with task-relevant information would presumably also be cognitively costly. Yet, it remains unclear whether the cognitive control demands involved in preventing and resolving conflict also constitute costs in value-based decisions. The present study investigated this question by embedding irrelevant distractors (flanker arrows) within a reversal-learning task, with intermixed free and instructed trials. Results showed that participants learned to adapt their free choices to maximize rewards, but were nevertheless biased to follow the suggestions of irrelevant distractors. Thus, the perceived cost of investing cognitive control to suppress an external suggestion could sometimes trump internal value representations. By adapting computational models of reinforcement learning, we assessed the influence of conflict at both the decision and learning stages. Modelling the decision showed that free choices were more biased when participants were less sure about which action was more rewarding. This supports the hypothesis that the costs linked to conflict management were traded off against expected rewards. During the learning phase, we found that learning rates were reduced in instructed, relative to free, choices. Learning rates were further reduced by conflict between an instruction and subjective action values, whereas learning was not robustly influenced by conflict between one's actions and external distractors. Our results show that the subjective cognitive control costs linked to conflict factor into value-based decision-making, and highlight that different types of conflict may have different effects on learning about action outcomes.

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Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis.

Publications

Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis.

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