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


Journal

PLoS medicine
ISSN: 1549-1676
Titre abrégé: PLoS Med
Pays: United States
ID NLM: 101231360

Informations de publication

Date de publication:
12 2020
Historique:
received: 12 09 2019
accepted: 02 11 2020
entrez: 2 12 2020
pubmed: 3 12 2020
medline: 2 2 2021
Statut: epublish

Résumé

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? 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 33264288
doi: 10.1371/journal.pmed.1003456
pii: PMEDICINE-D-19-03327
pmc: PMC7710036
doi:

Substances chimiques

Antitubercular Agents 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1003456

Subventions

Organisme : Medical Research Council
ID : MR/R008345/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : 1645544
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Lucia Cilloni (L)

MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.

Katharina Kranzer (K)

Clinical Research Department, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Biomedical Research and Training Institute, Harare, Zimbabwe.
Research Centre Borstel, Sülfeld, Germany.

Helen R Stagg (HR)

Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.

Nimalan Arinaminpathy (N)

MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.

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