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Managing Uncertainties Due to Limited Evidence in Economic Evaluations of Novel Anti-Tuberculosis Regimens: A Systematic Review.

ABSTRACT: BACKGROUND:Limited evidence for the implementation of new health technologies in low- and middle-income countries (LMICs) may lead to uncertainties in economic evaluations and cause the evaluations to produce inaccurate information for decision making. We performed a systematic review of economic evaluations on implementing new short-course regimens (SCR) for drug-sensitive and drug-resistant tuberculosis (TB), to explore how uncertainties due to the limited evidence in the studies were dealt with and to identify useful information for decision making from these studies. METHODS:We searched in electronic databases PubMed, EMBASE, NHSEED, and CEA registry for economic evaluations addressing the implementation of new anti-TB SCRs in LMICs published until September 2018. We included studies addressing both the cost and outcomes of implementing a new regimen for drug-sensitive and drug-resistant TB with a shorter treatment duration than the currently used regimens. The quality of the included studies was assessed using The Consensus Health Economic Criteria checklist. We extracted information from the included studies on uncertainties and how they were managed. The management of uncertainties was compared with approaches used in early health technology assessments (HTAs), including sensitivity analyses and pragmatic scenario analyses. We extracted information that could be useful for decision making such as cost-effectiveness conclusions, and barriers to implementing the intervention. RESULTS:Four of the 322 studies found in the search met the eligibility criteria. Three studies were model-based studies that investigated the cost effectiveness of a new first-line SCR. One study was an empirical study investigating the cost effectiveness of new regimens for drug-resistant TB. The model-based studies addressed uncertainties due to limited evidence through various sensitivity analyses as in early HTAs. They performed a deterministic sensitivity analysis and found the main drivers of the cost-effectiveness outcomes, that is, the rate of treatment default and treatment delivery costs. Additionally, two of the model-based studies performed a pragmatic scenario analysis and found a potential barrier to implementing the new first-line SCR, that is, a weak health system with a low TB care utilization rate. The empirical study only performed a few scenario analyses with different regimen prices and volumes of TB care utilization. Therefore, the study could only provide information on the main cost drivers. CONCLUSION:Using an approach similar to that used in early HTAs, where uncertainties due to the limited evidence are rigorously explored upfront, the economic evaluations could inform not only the decision to implement the intervention but also how to manage risks and implementation barriers.

SUBMITTER: Padmasawitri TIA

PROVIDER: S-EPMC7248140 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Managing Uncertainties Due to Limited Evidence in Economic Evaluations of Novel Anti-Tuberculosis Regimens: A Systematic Review.

Padmasawitri T I Armina TIA Saragih Sarah Maria SM Frederix Gerardus W GW Klungel Olaf O Hövels Anke M AM

PharmacoEconomics - open 20200601 2

<h4>Background</h4>Limited evidence for the implementation of new health technologies in low- and middle-income countries (LMICs) may lead to uncertainties in economic evaluations and cause the evaluations to produce inaccurate information for decision making. We performed a systematic review of economic evaluations on implementing new short-course regimens (SCR) for drug-sensitive and drug-resistant tuberculosis (TB), to explore how uncertainties due to the limited evidence in the studies were ...[more]

PMID: 31297751

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Project description:Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens.The emergence and spread of multidrug-resistant M. tuberculosis are a major threat to global public health. Linezolid is an oxazolidinone that is licensed for human use and has demonstrated potent activity against multidrug-resistant M. tuberculosis. However, long-term use of linezolid has shown to be toxic in patients, often resulting in thrombocytopenia. We examined therapeutic linezolid regimens in an in vitro model to characterize the exposure-toxicity relationship. The antibacterial activity against M. tuberculosis was also assessed for these regimens, including the amplification or suppression of resistant mutant subpopulations by the chosen regimen. Higher exposures of linezolid resulted in greater antibacterial activity, but with more toxicity and, for some regimens, increased resistant mutant subpopulation amplification, illustrating the trade-off between activity and toxicity. These findings can provide valuable insight for designing optimal dosage regimens for linezolid that are part of the long combination courses used to treat multidrug-resistant M. tuberculosis.

Project description:BackgroundMobile health (mHealth) is often reputed to be cost-effective or cost-saving. Despite optimism, the strength of the evidence supporting this assertion has been limited. In this systematic review the body of evidence related to economic evaluations of mHealth interventions is assessed and summarized.MethodsSeven electronic bibliographic databases, grey literature, and relevant references were searched. Eligibility criteria included original articles, comparison of costs and consequences of interventions (one categorized as a primary mHealth intervention or mHealth intervention as a component of other interventions), health and economic outcomes and published in English. Full economic evaluations were appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist and The PRISMA guidelines were followed.ResultsSearches identified 5902 results, of which 318 were examined at full text, and 39 were included in this review. The 39 studies spanned 19 countries, most of which were conducted in upper and upper-middle income countries (34, 87.2%). Primary mHealth interventions (35, 89.7%), behavior change communication type interventions (e.g., improve attendance rates, medication adherence) (27, 69.2%), and short messaging system (SMS) as the mHealth function (e.g., used to send reminders, information, provide support, conduct surveys or collect data) (22, 56.4%) were most frequent; the most frequent disease or condition focuses were outpatient clinic attendance, cardiovascular disease, and diabetes. The average percent of CHEERS checklist items reported was 79.6% (range 47.62-100, STD 14.18) and the top quartile reported 91.3-100%. In 29 studies (74.3%), researchers reported that the mHealth intervention was cost-effective, economically beneficial, or cost saving at base case.ConclusionsFindings highlight a growing body of economic evidence for mHealth interventions. Although all studies included a comparison of intervention effectiveness of a health-related outcome and reported economic data, many did not report all recommended economic outcome items and were lacking in comprehensive analysis. The identified economic evaluations varied by disease or condition focus, economic outcome measurements, perspectives, and were distributed unevenly geographically, limiting formal meta-analysis. Further research is needed in low and low-middle income countries and to understand the impact of different mHealth types. Following established economic reporting guidelines will improve this body of research.

Project description:PURPOSE:To present an analytical formalism for the in depth assessment of uncertainties of field output factors in small fields related to detector positioning based on dose profile measurements. Additionally, a procedure for the propagation of these uncertainties was developed. METHODS:Based on the assumption that one dimensional and two dimensional second-order polynomial functions can be fitted to dose profiles of small photon beams, equations for the calculation of the expectation value, the variance, and the standard deviation were developed. The following fitting procedures of the dose profiles were considered: A one-dimensional case (1D), a quasi two-dimensional case (2Dq) based on independently measured line profiles and a full 2D case (2Df) which also considers cross-correlations in a two-dimensional dose distribution. A rectangular and a Gaussian probability density function (PDF) characterizing the probability of possible positions of the detector relative to the maximum dose were used. Uncertainty components such as the finite resolution of the scanning water phantom, the reproducibility of the determination of the position of the maximum dose, and the reproducibility of the collimator system were investigated. This formalism was tested in a 0.5 x 0.5 cm2 photon field where dose profiles were measured using a radiochromic film, a synthetic diamond detector, and an unshielded diode detector. Additionally, the dose distribution measured with the radiochromic film was convoluted with a convolution kernel mimicking the active volume of the unshielded diode. RESULTS:Analytic expressions for the calculation of uncertainties on field output factors were found for the 1D, the 2Dq, and the 2Df case. The uncertainty of the field output factor related to the relative position of the detector to the maximum dose increased quadratically with increasing limits of possible detector positions. Analysis of the radiochromic film showed that the 2Dq case gave a more conservative assessment of the uncertainty compared to the 2Df case with a difference of < 0.1%. The 2Dq case applied to the film measurements agreed well with the same approach as was applied to the unshielded diode. The investigated uncertainty components propagated to an uncertainty of the field output factors of 0.5% and 0.4% for the synthetic diamond and the unshielded diode, respectively. Additionally, the expectation value was lower than the maximum dose. The difference was 0.4% and 0.3% for the synthetic diamond and the unshielded diode, respectively. CONCLUSIONS:The assessment of uncertainties of field output factors related to detector positioning is feasible using the proposed formalism. The 2Dq case is applicable when using online detectors. Accurate positioning in small fields is essential for accurate dosimetry as its related uncertainty increases quadratically. The observed drop of the expectation value needs to be considered in small field dosimetry.

Project description:BackgroundThe economic evaluation of health interventions is important in priority setting. Several guidance documents exist to support the conduct of economic evaluations, however, there is limited guidance for the evaluation of non-medical interventions. For tuberculosis (TB), where equity-deserving groups are disproportionately impacted, assessing interventions aimed at addressing social risk factors is necessary to effectively reduce TB burden.ObjectiveThis scoping review seeks to assess the existing literature on model-based economic evaluations of TB interventions to gauge the extent to which non-medical interventions have been evaluated in low-TB-incidence jurisdictions. As a secondary objective, this review aims to characterize key features of existing economic evaluations of medical and non-medical interventions.MethodsA literature search was conducted in the grey literature and MEDLINE, Embase, EconLit, and PsychINFO databases to September 6, 2022 following the Arksey and O'Malley framework. Eligible articles were those that used decision-analytic modeling for economic evaluation of TB interventions in low-TB-incidence jurisdictions.ResultsThis review identified 127 studies that met the inclusion criteria; 11 focused on prevention, 73 on detection, and 43 on treatment of TB. Only three studies (2%) evaluated non-medical interventions, including smoking reduction strategies, improving housing conditions, and providing food vouchers. All three non-medical intervention evaluations incorporated TB transmission and robust uncertainty analysis into the evaluation. The remainder of the studies evaluated direct medical interventions, eight of which were focused on specific implementation components (e.g., video observed therapy) which shared similar methodological challenges as the non-medical interventions. The majority of remaining evaluated medical interventions were focused on comparing various screening programs (e.g., immigrant screening program) and treatment regimens.ConclusionsThis scoping review identified a gap in literature in the evaluation of non-medical TB interventions. However, the identified articles provided useful examples of how economic modeling can be used to explore non-traditional interventions using existing economic evaluation methods.

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Managing Uncertainties Due to Limited Evidence in Economic Evaluations of Novel Anti-Tuberculosis Regimens: A Systematic Review.

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Managing Uncertainties Due to Limited Evidence in Economic Evaluations of Novel Anti-Tuberculosis Regimens: A Systematic Review.

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