Sarosh Nagar
David Nicholls
Dalia Dawoud- 1National Institute for Health and Care Excellence (NICE), London, United Kingdom
- 2Department of Chemistry & Department of Economics, Harvard College, Harvard University, Boston, MA, United States
- 3Faculty of Pharmacy, Cairo University, Cairo, Egypt
Objectives: The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development.
Methods: Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized.
Results: Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence.
Conclusion: Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.
Introduction
Tuberculosis (TB) is a highly infectious bacterial disease caused by the pathogen Mycobacterium tuberculosis (1). The disease infects over 10 million individuals worldwide and occurs when the bacterium infects individual’s lungs; however, initially, such infections are latent and asymptomatic as the infection is limited to the granuloma (2, 3). Over time, however, latent TB turns into active TB, resulting in coughing, fever, and other symptoms (4). Diagnosis of the disease usually occurs through a sputum culture, supplemented with additional tuberculin skin tests (TST), interferon-gamma assays (IGAs), and other approaches (5).
The discovery of streptomycin in 1944 opened the door to pharmacological treatments against TB, though initial trials identified that use of streptomycin alone induced antimicrobial resistance (AMR) (6). However, the use of para-aminosalicylic acid (PAS) with streptomycin soon introduced the concept of combination therapy using one or more pharmacological interventions, which was far more effective against the disease (7). Using these combination regimens, common anti-TB drugs, such as isoniazid, rifampin, and ethambutol, successfully reduced global TB burden for several decades (7). The global HIV-AIDS epidemic, however, introduced the risk of HIV-AIDS and TB co-infection, causing a rapid increase in TB prevalence, especially in developing nations (8). New infections were further driven by increasingly prevalent multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), which rendered traditional pharmacological interventions ineffective (9). A lack of investment in developing new antimicrobials against TB further compounded this problem — with only few products, introduced in the last 45 years against drug-resistant TB (10). The COVID-19 pandemic further disrupted global TB eradication efforts and fueled a surge of infections (11).
In response to this increasing global prevalence of tuberculosis, pharmaceutical companies and governments are trying to accelerate the development of novel treatments against tuberculosis through public-private partnership projects like the European Regimen Accelerator for Tuberculosis (ERA4TB) (12). However, access to these novel regimens will only be possible if they are cost-effective and of demonstrated value compared to currently available regimens. To assess this, Health technology assessment (HTA) agencies, that currently exist in many countries to facilitate evidence-informed decision making regarding the allocation of the scarce health system resources, need to understand the key drivers of cost effectiveness of TB treatments and any additional value attributes.
While there have been several past systematic reviews of economic evaluations of treatments for latent TB or both active and latent TB, reviews that focused specifically on active tuberculosis are much rarer (13, 14). The most recent review by Byun et al. focused on active TB but included both pharmacological and non-pharmacological treatments (15). Additionally, to our knowledge, no reviews of published HTA reports of active TB treatments have been published so far.
Therefore, to inform novel regimen development activities and facilitate future appraisals of such novel pharmacological interventions for active TB, we conducted this systematic review. It aimed to describe economic evaluation approaches used in past studies and HTA reports, identify estimates and key drivers of the cost effectiveness and value attributes of pharmacological interventions against TB.
Methods
PICOS
This systematic review qualitatively synthesized past economic evaluations of pharmacological treatments of active TB. A review protocol was developed to define the Population, Intervention, Comparator, Outcomes, Study design (PICOS) of the studies to include. Given the limited time available for this review, which was conducted as part of a summer internship, and to minimize research waste, it was conducted as an update of the most recently published systematic review of economic evaluation on the topic and supplemented by a de-novo review of HTA reports and the gray literature. Thus, we started by conducting a rapid review to identify the most relevant and recent systematic review that aligns with our review protocol to update it. Through this initial stage, we identified that the most recent systematic review of interventions for active TB was the one performed by Byun et al., which identified relevant economic evaluations published until January 1st, 2020 (15).
As the scope of Byun et al. review covered both pharmacological and non-pharmacological treatment strategies and interventions for active TB, we only focused on its included studies involving pharmacological interventions (15). We then conducted a systematic search to identify all relevant economic evaluations published after its search cut-off date until June 2022.
Search strategy & information sources
The search strategy was designed to identify all economic evaluations of pharmacological treatments of any form of active TB, including multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). We searched six databases: MEDLINE (Ovid), MEDLINE-In Process (OVID), MEDLINE Epub Ahead of Print (Ovid), EMBASE (Ovid), Cochrane Database of Systematic Reviews (Cochrane) and Econlit (Ovid). Published HTA reports were identified through searching the International HTA Database (International Network of Agencies for Health Technology Assessment). Citation referencing and checking was performed on included studies. The search was conducted on June 13th and 14th, 2022.
The search strategy was structured based on the National Institute for Health and Care Excellence’s existing TB population search strategy (used in the 2016 NICE NG33 guidelines for the management of TB) and its most recent economic evaluation search strategies that were used in recently published systematic reviews (16–18). This strategy consisted of using terms related to TB (e.g., mycobacterium), disease pathology (e.g., phlegm), or existing disease diagnosis techniques (e.g., bronchoalveolar lavage), and pairing these search terms with existing terms related to current antitubercular agents (e.g., isoniazid). We then applied economic evaluation filters to these results. We limited results to articles published in English after January 1st, 2020.
The search for HTA reports was conducted in the International HTA database, utilizing a search string focused on TB or synonymous names for the disease. Further detail on all search strategies can be found in the Supplemental material.
Eligibility criteria
Our review protocol specified that studies can be included if they were full economic evaluations (including cost-minimization, cost-utility, cost-effectiveness, cost–benefit, and cost-consequence studies) or cost-comparison studies evaluating two or more pharmaceutical interventions designed to treat one or more suspected or confirmed active variants of mycobacterium tuberculosis.
Studies were excluded based on the first criteria they met in the following order:
1. The target population did not have tuberculosis.
2. The intervention was a diagnostic technology, a preventive intervention (e.g., vaccines), or a public health intervention (e.g., face coverings, population screening).
3. The study was a partial economic evaluation.
4. The study was a modeling study that predicted epidemiological outcomes over time without an economic evaluation.
5. The study was a poster abstract that did not provide sufficient methodological detail.
6. The study was a letter to the editor, commentary, or editorial.
Results were first screened under the selection criteria by one reviewer (S.N.) based on titles and abstracts, with a second reviewer (D.D.) reviewing 10% of the previous sample to ensure screening was done correctly. Records that potentially met inclusion criteria were assessed in full. The decision to exclude studies after full-text review was done by both reviewers, with any remaining disagreements resolved through discussion. Data extraction was performed on included studies. Studies included in the Byun et al. review were reassessed using the same criteria, for inclusion in our review (15).
Data extraction
Data extracted from the published studies included study characteristics, consisting of the country, currency, setting, interventions and comparators, type of economic evaluation, analysis approach, study perspective, model time horizon, cost categories, cost year, discounting rates, health outcomes, and sources of efficacy and utility data (see Table 1). Study results were also collected, consisting of cost and health outcome results, incremental cost-effectiveness ratios, net benefits of interventions versus, comparators, cost-effectiveness thresholds, sensitivity and scenario analysis, the authors’ conclusions regarding cost-effectiveness, and the authors’ reported limitations and challenges (see Table 2).
Table 1. Background details of included studies.
Table 2. Summary of the results of included studies.
Quality assessment
We also assessed the quality of all included studies using the methodological limitations checklist provided by the NICE guidelines manual (39). Studies were evaluated to have either minor, potentially serious, or very serious limitations based on study characteristics, including sources of outcomes data, study assumptions, whether incremental cost-effectiveness ratios (ICERs) were reported, the relative rigor of sensitivity and scenario analyses. Completed methodological quality assessment of all included studies can be found in the Supplemental material.
Data extracted from the HTA reports included the intervention and comparator evaluated, the value elements discussed in each HTA report, and the final recommendation on the cost-effectiveness and value of the appraised intervention.
Results
Search results
Our search returned 991 published studies, which was combined with the 17 previous studies identified from the past systematic review by Byun et al. (15). After screening, 20 total studies were included in the review, as described in the PRISMA flowchart (see Figure 1). The most common reason for exclusion of published studies was that studies were either not focused specifically on active TB or were not an economic evaluation.
Figure 1. PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases, registers and other.
A total of 53 HTA reports was found from our search of the INAHTA database, of which 50 were excluded, most commonly because evaluations focused on latent tuberculosis or non-pharmacological interventions. Therefore, 20 published studies were considered potentially includable in our review (19–38). Of the 20 studies, 4 studies were found to have minor limitations, while 14 studies were found to have potentially serious limitations, and 2 studies were found to have very serious limitations (19–38). Methodological quality limitations commonly found in studies included short time horizons, omission of relevant outcomes, or suboptimal sources of outcome and intervention effects data. The characteristics of the included studies are summarized in Table 1.
Study characteristics
Sixteen studies out of 20 conducted cost-utility analyses, while 6 conducted cost-effectiveness analyses and 2 conducted cost-comparison analyses, while some studies conducted multiple analyses. Twelve studies used a multi-state Markov model to simulate TB infection and recovery, while 4 studies used a decision tree model that combined various outcomes weighted based on probabilities to estimate cost-effectiveness. Two studies reported economic evaluations conducted alongside randomized control trials (RCTs). Nineteen out of 20 studies did not specify a specific patient population, while 2 studies focused on patients receiving ambulatory treatment.
Ten out of 20 studies specifically focused on MDR-TB or XDR-TB while 11 remaining studied all forms of active TB. Studies were conducted across a large variety of international settings, with South Africa being the most common setting (7 out of 20). Most studies occurred in the year 2017 (5 out of 20) and results were reported in USD ($) (15 out of 20). Most studies also adopted a healthcare perspective (13 out of 20) as the sole or main perspective, while a smaller portion of studies only used a societal perspective (6 out of 20).
Of the 3 HTA reports evaluated, two reports evaluated the value of bedaquiline relative to background regimens (40, 41). The third HTA report by EUnetHTA evaluated the combination of a pretomanid, bedaquiline, and linezolid (BPaL) regimen against three comparator regimens of various common tuberculosis medications (42). Due to heterogeneity in the content of HTA reports, HTA results were not included in Tables 1, 2 (40–42).
Given the extensive heterogeneity and significant limitations posed when attempting quantitative synthesis of cost-effectiveness estimates, we conducted a qualitative, narrative synthesis of included studies. See Table 2 for summary of studies’ results.
Cost-effectiveness of bedaquiline
Eleven of 20 studies evaluated the cost-effectiveness of bedaquiline versus a background regimen (BR) or other standard-of-care regimens. Codecasa et al. found that addition of bedaquiline to background regimen (BBR) in an Italian setting was cost-effective in 88 and 96% of cases, respectively, at thresholds of 40,000 EUR/life-year gained (LYG) and 60,000 EUR/LYG, with BBR having an ICER of 15,684 EUR/quality-adjusted life year (QALY) from a healthcare perspective and 3,847 EUR/QALY from a societal perspective (27). Park et al. similarly found that addition of bedaquiline to a standard regimen in a Korean setting was cost-effective in a majority of cases at a threshold of 26 million KRW with an ICER of 10,822,992 KRW/LYG (25). Wolfson similarly found in a British setting that addition of bedaquiline to a background regimen dominated a background regimen at thresholds of 20,000 and 30,000 GBP/QALY, with an ICER of 10,0008.75 GBP/QALY gained (22).
Schippel et al. drew similar conclusions South African setting, finding that adding bedaquiline to a standard regimen have an ICER of $1,242/disability-adjusted life-year (DALY) for patients with MDR/RR-TB, making it cost-effective at a threshold of 1 GDP (gross domestic product) per capita equal to $5,718 (29). A follow-up analysis in Schippel et al. also found that the cost-effectiveness of adding bedaquiline to existing regimens increased if the effects of adverse reactions to pharmacological treatments were included in cost-effectiveness determinations (30). Fan et al. agreed with this analysis in a Hong Kong setting, finding bedaquiline’s addition to a background regimen had an ICER of $12/QALY and was cost-effective in 99.98% of cases at a threshold of one GDP per capita equal to $46,182 (32). Agnarson et al. similarly found that bedaquiline was cost-effective over a generic injectable short-course regimen with an ICER of $982 USD/DALY at a threshold of $6,160 (34).
Other studies found similar results even when comparing the addition of bedaquiline to background regimen against other tuberculosis drugs. Wirth et al. found that, in a German setting, a bedaquiline plus background regimen strategy dominated both a linezolid plus background regimen and bedaquiline plus background regimen strategy with an ICER of 22,238 EUR/QALY gained at thresholds of both 30,000 and 50,000 EUR/QALY gained (31). Gomez et al. conducted a cost-comparison analysis in a six-country setting and similarly estimated that the addition of bedaquiline to a regimen of pretomanid and linezolid was most likely to be cost-effective compared to local standards of care (38). More pessimistically, a cost comparison analysis by Manalan et al. in a UK setting found bedaquiline to be cost-neutral compared to current injectable regimens (33).
Only one study, Lu et al., found mixed evidence on the cost-effectiveness of bedaquiline, finding adding the drug to standard regimens to be cost-effective in 32–94% of cases across four international settings (Estonia, China, Russia, and Peru) depending on if a threshold of one or three times GDP per capita was used (28). Lu et al. did not calculate an ICER for bedaquiline (28).
Cost-effectiveness of shorter vs. longer duration regimens
Six studies evaluated the cost-effectiveness of using short-course regimens versus long-course regimens for the treatment of MDR-TB and XDR-TB. Knight et al. found that in a South African setting, a shorter 4 month-regimen was likely to be cost-effective over a 6-month regimen with an ICER of $436/DALY at a threshold of $6,618 (23). Gomez et al. also found a shorter regimen to be cost-effective across several settings at a threshold of one GDP per capita in each country (26). Cost-comparison analysis found similar results as well, with both Bada et al., in a Nigerian setting, and Madan et al. in an Ethiopian and South African setting finding that short-course treatment regimens were likely more cost-effective than longer regimens (35, 37). This result also aligned with the hypothetical modeling in Owens et al., which analyzed a hypothetical shorter-duration, higher-cost treatment in a hypothetical country setting and found the shorter regimen to be cost-effective as well (21). Only Reddy et al. contradicted these findings in a South African setting and found a 6-month regimen dominated a 4-month regimen at a $940/LYG threshold (36).
Cost-effectiveness of ethambutol
Two studies assessed the cost-effectiveness of ethambutol as compared to other interventions. Law et al. found that ethambutol, when added to a standard WHO regimen, was least likely to be cost-effective at threshold of one GDP per capita in an Ecuadorian setting (20). Manabe et al. found that a 4-month regimen of isoniazid plus rifampicin dominated a 6-month regimen of isoniazid plus ethambutol by comparing mortality rates and costs of treatment (19). Both results suggest than ethambutol may not be a cost-effective addition to most standard TB treatment regimens.
Cost-effectiveness of delamanid
Lastly, one remaining study, Diel studied the value of delamanid and found that addition of the drug to existing background regimens dominated existing background regimens in a German setting with an ICER of 3,494 EUR/QALY at a threshold of 10,000 EUR (24). However, as Diel was the only study in our sample to study Delamanid, it is difficult to draw conclusions on the cost-effectiveness of delamanid or its future role in treatment regimens (24).
Sensitivity analysis
Probabilistic and deterministic sensitivity analyses found that the cost-effectiveness determinations were largely stable, but were sensitive to several key factors depending on the intervention being evaluated. For adding bedaquiline to background or standard regimens, cost-effectiveness determinations were most sensitive to the number of TB cases and the proportion of cases with sputum culture conversion (25, 27). For studies evaluating the cost-effectiveness of shorter versus longer regimens for MDR-TB, results were most-sensitive to existing health service costs, drug costs, treatment delivery costs, and treatment efficacy in limiting recurrent-TB mortality (37, 38).
Findings from HTA reports
Lastly, the HTA reports found similar results to the aforementioned studies. The HTA report by EUNEHTA in 2020 found that the BpaL regimen had a high rate of cost-effectiveness relative to existing background regimens (42). The report from the German G-BA comparing bedaquiline to an unspecified background regimen found a non-quantifiable additional benefit from the addition of bedaquiline (41). The HTA report by the All Wales Medicines Strategy Group (AWMSG) similarly recommended bedaquiline over multiple background regimens (40).
Discussion
This study synthesizes 20 economic evaluations and 3 HTA reports evaluating various pharmacological interventions for TB. Heterogeneity and variation in studies prevent the quantitative synthesis of our results, but several broad trends are observable.
For the addition of bedaquiline to background regimens or standard regimens for TB, clinical evidence on bedaquiline’s efficacy has been limited (43). However, nearly all studies in our review found the addition of bedaquiline to existing background or standard regimens against drug-resistant TB was cost-effective across a variety of international settings (22, 25, 27, 29–34, 38). Bedaquiline also became cost-effective in a greater number of cases if analyses accounted for adverse reactions (30). Bedaquiline’s high cost-effectiveness, thus, despite limited clinical evidence, may justify a slightly higher value-based price. Similarly, this result highlights a need for effective antimicrobial stewardship to limit the prevalence of bedaquiline-resistant strains and maintain the drug’s effectiveness and, hence, its cost-effectiveness.
For the question of short-course versus long-course treatment regimens, our findings broadly support the conclusion that shorter-course regimens may be more effective, even if a shorter-course regimen was more expensive than its longer counterpart. Even in Reddy et al., where a longer regimen dominated a shorter one, suggested that a shorter-regimen may be more cost-effective if patient loss to follow-up/drop out was accounted for in the model. (44) This result suggests that evidence-based clinical guidelines could consider shortening treatment regimens, especially in low-resource settings, to maximize the number of lives saved given limited resources. Lastly, our findings for ethambutol finds that addition of the drug to existing TB regimens is not likely to be cost-effective, but our analysis is based on solely two studies and hence are not conclusive of the drug’s value (19, 20).
This review also highlights more specific gaps in current economic evaluations of treatments for active tuberculosis. First, most studies did not consider the transmission costs of TB in their models — a uniquely problematic oversight due to the disease’s high infectivity and latency periods (1–3). Acc-ounting for these transmission costs may alter the cost-effectiveness of various TB treatments depending on the stage at which interventions successfully treat TB. Second, no study accounted for the potential costs of AMR— an important and common oversight for antimicrobial drugs like bedaquiline, where the treatment’s relative novelty should create an impetus for proper stewardship policies to limit the advent of drug-resistant strains. Third, only one study, Schippel et al. accounted for the costs of adverse reactions (30). Given that many standard tuberculosis regimens can have several adverse effects, and even new drugs like bedaquiline can induce corrected QT prolongations, hyperlactatemia, and more, accounting for such effects is integral to future cost-effectiveness analyses (45).
Beyond specific interventions for TB, this systematic review highlights a strong need for novel pharmacological interventions for active TB. Of the interventions in our review, the only drug with favorable cost-effectiveness across multiple settings was bedaquiline, with other interventions displaying more unclear results. Given that bedaquiline is a single drug against which resistant strains have already emerged, our results highlight a need for pharmaceutical companies and governments to accelerate the development of novel MDR-TB and XDR-TB treatments (46). Such developments would help ease reliance on bedaquiline as a last-resort treatment for drug-resistant TB and may prove more efficacious in treating future drug-resistant strains.
The HTA reports find similar results to those in the studies. Two out of three HTA reports deemed bedaquiline to be cost-effective compared to existing comparators and background regimens (40–42). The third report similarly found bedaquiline to be cost-effective as part of a combination BPaL regimen, but further studies are likely needed to more strongly characterize BpaL’s cost-effectiveness relative to existing background regimens (40–42). Additionally worth noting is that many core elements of value — including scientific spillovers, productivity effects, family spillovers, equity, and more were not discussed by any HTA reports. This result may highlight a current deficiency with existing HTA appraisal strategies, and suggests that existing HTA agencies should consider considering additional elements of value in appraisal decisions. However, given that our sample size is limited, we cannot make a definitive conclusion on this matter.
Limitations
This review has a number of limitations. We excluded studies that were not published in English, were abstracts with insufficient detail or were preprints. Our decision to omit such studies may have limited our ability to identify papers from foreign nations, especially in several non-English countries which may have TB incidence, influencing the results of our analysis (8). Lastly, our analysis is certainly not definitive as to the cost-effectiveness of various pharmacological interventions for TB. There is limited clinical evidence for the efficacy of drugs like bedaquiline, and as new pharmacological interventions are developed, and new data emerges, such findings are likely to influence cost-effectiveness determinations. Moreover, conducting economic evaluations in the context of anti-tuberculosis interventions can often face difficulties, such as limited data on the efficacy of a given intervention vs. a comparator (23).
Despite these limitations, this review provides the most comprehensive overview of the economic evidence available relating to cost effectiveness of pharmacological treatments of active TB, the key drivers of the results and the additional value attributes to consider when assessing these treatments by HTA agencies. Optimizing the development of novel treatment regimens to address these value attributes will be key in ensuring positive assessment outcomes, which in turn will lead to prompt patient access to these treatments particularly in resource limited settings.
Conclusion
Our review of economic evaluations of pharmacological interventions for active drug-resistant TB shows that the addition of bedaquiline to existing background or standard regimens for drug-resistant TB is likely to be highly cost-effective across a number of international settings. However, such findings are tempered by the limited clinical evidence collected on the real-world effectiveness of bedaquiline. It also shows that shortening TB treatment regimens, especially in low-resource settings, may be a cost-effective strategy, while we lack sufficient evidence to draw strong conclusions about the cost-efficacy of other drugs like ethambutol and delamanid.
These results highlight a need for both the private and public sector to support the development of novel antimicrobial treatments against active drug-resistant TB, especially given the limited number of cost-effective treatments for MDR-TB and XDR-TB present at this time. Our results also highlight a growing need for economic modeling to consider the costs of transmission, antimicrobial resistance, and adverse events, especially given the relevance of all three cost categories for pharmacological interventions against active TB. Lastly, our results also suggest that in certain resource poor settings, scientists ought to consider the feasibility of shortening treatment regimens to maximize the number of lives saved while ensuring efficient allocation of resources. Such policy steps could ensure that the world has the necessary innovation and resources to combat drug-resistant tuberculosis in an evidence-based and equitable manner.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.
Author contributions
SN: Data curation, Methodology, Conceptualization, Formal analysis, Writing – original draft. DN: Data curation, Methodology, Writing – review & editing. DD: Data curation, Methodology, Supervision, Conceptualization, Formal analysis, Validation, Funding acquisition, Resources, Writing – review & editing.
Funding
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 853989. The JU receives support from the European Union’s Horizon 2020 Research and Innovation Programme and EFPIA and Global Alliance for TB Drug Development Non-Profit Organisation, Bill & Melinda Gates Foundation, University of Dundee.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Author disclaimer
This work reflects only the author’s views, and the JU is not responsible for any use that may be made of the information it contains.
Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2024.1201512/full#supplementary-material
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Keywords: tuberculosis, anti-microbial resistance, public health, economic evaluations, systematic review, cost effectiveness, value attributes
Citation: Nagar S, Nicholls D and Dawoud D (2024) A systematic review of economic evaluations of pharmacological treatments for active tuberculosis. Front. Public Health. 12:1201512. doi: 10.3389/fpubh.2024.1201512
Edited by:
Claudiu Morgovan, Lucian Blaga University of Sibiu, RomaniaReviewed by:
Nattiya Kapol, Silpakorn University, ThailandMalaisamy Muniyandi, National Institute of Research in Tuberculosis (ICMR), India
Copyright © 2024 Nagar, Nicholls and Dawoud. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Dalia Dawoud, Dalia.Dawoud@nice.org.uk