Health-economic modelling of infectious disease diagnostics: current approaches and future opportunities

Objectives: Antimicrobial resistance (AMR) is a public health threat; infections with resistant organisms are estimated to cause over 650.000 infections and over 30.000 deaths in Europe. AMR is associated with antibiotic consumption: appropriate prescribing of antibiotics is key in combating AMR. To fight this threat, it has been suggested that point-of-care diagnostics to inform antibiotics prescribing are an important tool in reducing antibiotics prescriptions. With the objective of knowing the state of the art, we reviewed diagnostic cost-effectiveness analyses (CEAs) for infectious disease, focussing on model types, effects on prescriptions and AMR.  Methods: We searched the literature comprehensively through the PUBMED, Web of Science and EMBASE databases, as well as grey literature for the period 2000-2018. We included economic evaluations for diagnostic strategies for infectious disease in all geographic areas. Data extraction was based on the Consolidated Health Economic Evaluation Reporting Standards statement, with an additional focus on the modelling type and inclusion of AMR.Results: In general, CEAs of diagnostics for infectious disease fall in two categories: trial-based cost-effectiveness, focusing on short-term outcomes, and long-term models, focusing on outcomes extrapolated beyond the trial. Outcomes measured are for example prescriptions saved or hospitalizations saved. Cost-utility analyses seem to be difficult, as QALY differences between various diagnostic strategies are minor. Antimicrobial resistance is considered indirectly: as an ICER with prescriptions saved as an outcome; by calculating the threshold cost of resistance that would change the conclusion of cost-effectiveness; or as a point estimate; often, it is not considered at all.Conclusions: CEAs of diagnostic strategies for infectious disease are relatively scarce and it can be challenging to prove the cost-effectiveness of diagnostic strategies, especially in the context of relatively inexpensive treatments, such as antibiotics. However, there is an important opportunity of including the societal costs of AMR in future CEAs.<br/

Cost-effectiveness and budget impact of a lifestyle intervention to improve cardiometabolic health in patients with severe mental illness

Introduction: This study assessed the cost-effectiveness and budget impact of a lifestyle intervention to improve cardiometabolic health in severe mentally ill (SMI) patients in the LION trial.Methods: Patients (n = 244) were randomized to receive either care-as-usual or a lifestyle intervention in which mental health nurses coached patients in changing their lifestyle by using a web tool. Costs and quality of life were assessed at baseline and at 6 and 12 months. Incremental costs per centimeter waist circumference (WC) lost and per Quality-Adjusted Life Year (QALY) gained were assessed. Budget impact was estimated based on three intervention-uptake scenarios using a societal and a third-party payer perspective.Results: Costs and reduction in WC were higher in the intervention (n = 114) than in the control (n = 94) group after 12 months, although not statistically significant, resulting in (sic)1,370 per cm WC lost. QALYs did not differ between the groups, resulting in a low probability of the intervention being cost-effective in cost/QALY gained. The budget impact analysis showed that for a reasonable participation of 43%, total costs were around (sic)81 million over 5 years, or on average (sic)16 million annually (societal perspective).Conclusions: The intervention is not cost-effective at 12 months and the budget impact over 5 years is substantial. Possibly, 12 months was too short to implement the intervention, improve cardiometabolic health, and reduce care costs. Therefore, the incentive for this intervention cannot be found in short-term financial advantages. However, there may be benefits associated with lifestyle interventions in the long term that remain unclear.</p

Evaluations of training and education interventions for improved infectious disease management in low-income and middle-income countries:a systematic literature review

OBJECTIVES: To identify most vital input and outcome parameters required for evaluations of training and education interventions aimed at addressing infectious diseases in low-income and middle-income countries. DESIGN: Systematic review. DATA SOURCES: PubMed/Medline, Web of Science and Scopus were searched for eligible studies between January 2000 and November 2021. STUDY SELECTION: Health economic and health-outcome studies on infectious diseases covering an education or training intervention in low-income and middle-income countries were included. RESULTS: A total of 59 eligible studies covering training or education interventions for infectious diseases were found; infectious diseases were categorised as acute febrile infections (AFI), non-AFI and other non-acute infections. With regard to input parameters, the costs (direct and indirect) were most often reported. As outcome parameters, five categories were most often reported including final health outcomes, intermediate health outcomes, cost outcomes, prescription outcomes and health economic outcomes. Studies showed a wide range of per category variables included and a general lack of uniformity across studies. CONCLUSIONS: Further standardisation is needed on the relevant input and outcome parameters in this field. A more standardised approach would improve generalisability and comparability of results and allow policy-makers to make better informed decisions on the most effective and cost-effective interventions

Study on intracranial meningioma using PET ligand investigation during follow-up over years (SIMPLIFY)

Purpose Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of C-11-methionine positron emission tomography (MET-PET) to the regular MRI follow-up. Methods This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and C-11-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's kappa. Results Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUVpeak T/N-cortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A kappa of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data. Conclusion In this pilot study, C-11-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging

Correction to:Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

After publication of our article [1] we were notified that Figure 1 was wrongly presented

Oral esketamine for treatment-resistant depression:rationale and design of a randomized controlled trial

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016