Lessons Learned from Model-based Economic Evaluations of COVID-19 Drug Treatments Under Pandemic Circumstances: Results from a Systematic Review.

BACKGROUND: Following clinical research of potential coronavirus disease 2019 (COVID-19) treatments, numerous decision-analytic models have been developed. Due to pandemic circumstances, clinical evidence was limited and modelling choices were made under great uncertainty. This study aimed to analyse key methodological characteristics of model-based economic evaluations of COVID-19 drug treatments, and specifically focused on modelling choices which pertain to disease severity levels during hospitalisation, model structure, sources of effectiveness and quality of life and long-term sequelae. METHODS: We conducted a systematic literature review and searched key databases (including MEDLINE, EMBASE, Web of Science, Scopus) for original articles on model-based full economic evaluations of COVID-19 drug treatments. Studies focussing on vaccines, diagnostic techniques and non-pharmaceutical interventions were excluded. The search was last rerun on 22 July 2023. Results were narratively synthesised in tabular form. Several aspects were categorised into rubrics to enable comparison across studies. RESULTS: Of the 1047 records identified, 27 were included, and 23 studies (85.2%) differentiated patients by disease severity in the hospitalisation phase. Patients were differentiated by type of respiratory support, level of care management, a combination of both or symptoms. A Markov model was applied in 16 studies (59.3%), whether or not preceded by a decision tree or an epidemiological model. Most cost-utility analyses lacked the incorporation of COVID-19-specific health utility values. Of ten studies with a lifetime horizon, seven adjusted general population estimates to account for long-term sequelae (i.e. mortality, quality of life and costs), lasting for 1 year, 5 years, or a patient's lifetime. The most often reported parameter influencing the outcome of the analysis was related to treatment effectiveness. CONCLUSION: The results illustrate the variety in modelling approaches of COVID-19 drug treatments and address the need for a more standardized approach in model-based economic evaluations of infectious diseases such as COVID-19. TRIAL REGISTRY: Protocol registered in PROSPERO under CRD42023407646.

The value of artificial intelligence for the treatment of mechanically ventilated intensive care unit patients: An early health technology assessment.

PURPOSE: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients. MATERIALS AND METHODS: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death. The model simulates two scenarios, care as usual and care with the AI system, and compares these scenarios to estimate their cost-effectiveness. RESULTS: The generic health-economic model we developed is suitable for estimating the cost-effectiveness of various AI systems. By varying input parameters and assumptions, the model can examine the cost-effectiveness of AI systems across a wide range of different clinical settings. CONCLUSIONS: Using the proposed generic health-economic model, investors and innovators can easily assess whether implementing a certain AI system is likely to be cost-effective before an exact clinical impact is determined. The results of the early HTA can aid investors and innovators in deployment of AI systems by supporting development decisions, informing value-based pricing, clinical trial design, and selection of target patient groups.

Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension.

About one-third of patients with depression do not achieve adequate response to current treatment options. Although intravenous and intranasal administrations of (es)ketamine have shown antidepressant properties, their accessibility and scalability are limited. We investigated the efficacy, safety, and tolerability of generic oral esketamine in patients with treatment-resistant depression (TRD) in a randomized placebo-controlled trial with open-label extension. This study consisted of 1) a six-week fixed low-dose treatment phase during which 111 participants received oral esketamine 30 mg or placebo three times a day; 2) a four-week wash-out phase; and 3) an optional six-week open-label individually titrated treatment phase during which participants received 0.5 to 3.0 mg/kg oral esketamine two times a week. The primary outcome measure was change in depressive symptom severity, assessed with the Hamilton Depression Rating Scale (HDRS17), from baseline to 6 weeks. Fixed low-dose oral esketamine when compared to placebo had no benefit on the HDRS17 total score (p = 0.626). Except for dizziness and sleep hallucinations scores, which were higher in the esketamine arm, we found no significant difference in safety and tolerability aspects. During the open-label individually titrated treatment phase, the mean HDRS17 score decreased from 21.0 (SD 5.09) to 15.1 (SD 7.27) (mean difference -6.0, 95% CI -7.71 to -4.29, p < 0.001). Our results suggest that fixed low-dose esketamine is not effective in TRD. In contrast, individually titrated higher doses of oral esketamine might have antidepressant properties.

Mechanical ventilation as a major driver of COVID-19 hospitalization costs: a costing study in a German setting.

BACKGROUND: While COVID-19 hospitalization costs are essential for policymakers to make informed health care resource decisions, little is known about these costs in western Europe. The aim of the current study is to analyze these costs for a German setting, track the development of these costs over time and analyze the daily costs. METHODS: Administrative costing data was analyzed for 598 non-Intensive Care Unit (ICU) patients and 510 ICU patients diagnosed with COVID-19 at the Frankfurt University hospital. Descriptive statistics of total per patient hospitalization costs were obtained and assessed over time. Propensity scores were estimated for length of stay (LOS) at the general ward and mechanical ventilation (MV) duration, using covariate balancing propensity score for continuous treatment. Costs for each additional day in the general ward and each additional day in the ICU with and without MV were estimated by regressing the total hospitalization costs on the LOS and the presence or absence of several treatments using generalized linear models, while controlling for patient characteristics, comorbidities, and complications. RESULTS: Median total per patient hospitalization costs were €3,010 (Q1 - Q3: €2,224-€5,273), €5,887 (Q1 - Q3: €3,054-€10,879) and €21,536 (Q1 - Q3: €7,504-€43,480), respectively, for non-ICU patients, non-MV and MV ICU patients. Total per patient hospitalization costs for non-ICU patients showed a slight increase over time, while total per patient hospitalization costs for ICU patients decreased over time. Each additional day in the general ward for non-ICU COVID-19 patients costed €463.66 (SE: 15.89). Costs for each additional day in the general ward and ICU without and with mechanical ventilation for ICU patients were estimated at €414.20 (SE: 22.17), €927.45 (SE: 45.52) and €2,224.84 (SE: 70.24). CONCLUSIONS: This is, to our knowledge, the first study examining the costs of COVID-19 hospitalizations in Germany. Estimated costs were overall in agreement with costs found in literature for non-COVID-19 patients, except for higher estimated costs for mechanical ventilation. These estimated costs can potentially improve the precision of COVID-19 cost effectiveness studies in Germany and will thereby allow health care policymakers to provide better informed health care resource decisions in the future.

A blended module (STAIRS) to promote functional and personal recovery in patients with a major depressive disorder in remission: study protocol of a concurrent mixed methods randomized controlled trial.

BACKGROUND: Despite the availability of a wide variety of evidence-based treatments for major depressive disorder (MDD), many patients still experience impairments in their lives after remission. Programs are needed that effectively support patients in coping with these impairments. The program Storytelling and Training to Advance Individual Recovery Skills (STAIRS) was developed to address this need and combines the use of peer contact, expert-by-experience guidance, family support and professional blended care. The aim of the planned study is (1) to assess the efficacy of the STAIRS program in patients with remitted MDD, (2) to investigate patients' subjective experiences with STAIRS, and (3) to evaluate the program's cost-effectiveness. METHODS: A concurrent mixed-methods randomized controlled trial design will be used. Patients aged between 18 and 65 years with remitted MDD (N = 140) will be randomized to either a group receiving care as usual (CAU) + the STAIRS-program or a control group receiving CAU + some basic psychoeducation. Quantitative efficacy data on functional and personal recovery and associated aspects will be collected using self-report questionnaires at the start of the intervention, immediately following the intervention, and at the six-month follow-up. Insights into patients' experiences on perceived effects and the way in which different program elements contribute to this effect, as well as the usability and acceptability of the program, will be gained by conducting qualitative interviews with patients from the experimental group, who are selected using maximum variation sampling. Finally, data on healthcare resource use, productivity loss and quality of life will be collected and analysed to assess the cost-effectiveness and cost-utility of the STAIRS-program. DISCUSSION: Well-designed recovery-oriented programs for patients suffering from MDD are scarce. If efficacy and cost-effectiveness are demonstrated with this study and patients experience the STAIRS program as usable and acceptable, this program can be a valuable addition to CAU. The qualitative interviews may give insights into what works for whom, which can be used to promote implementation. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on 1 July 2021, registration number NCT05440812.

Cost-effectiveness analysis of a first-trimester screening test for preterm preeclampsia in the Netherlands.

OBJECTIVES: The risk of preterm preeclampsia (PT PE) can significantly be reduced by starting acetylsalicylic acid ≤ 16 weeks of gestational age. First trimester predictive models based on maternal risk factors to effectively start this therapy lacked sufficient power, but recent studies showed that these models can be improved by including test results of biochemical and/or -physical markers. To investigate whether testing a biochemical marker in the first trimester is cost-effective in the Netherlands, a cost-effectiveness analysis was performed in this study. STUDY DESIGN: The outcome of this study was expressed as an incremental cost-effectiveness ratio (ICER) with as effect prevented PT PE cases. To evaluate the impact of each model parameter and to determine model uncertainties, both univariate and probabilistic sensitivity analyses were performed. RESULTS: When compared to the baseline strategy, the test strategy is estimated to save almost 4 million euros per year on a national scale and at the same time this would prevent an additional 228 PT PE cases. The sensitivity analyses showed that the major drivers of the result are the costs to monitor a high-risk pregnancy and the specificity and that most of the model simulations were in the southeast quadrant: cost saving and more prevented complications. CONCLUSIONS: This study showed that a first-trimester test strategy to screen for PT PE in the first trimester is potentially cost-effective in the Dutch healthcare setting. The fact that the specificity is a major driver of the ICER indicates the importance for a (new) screening model to correctly classify low-risk pregnancies.

Early Detection of Breast Cancer in Indonesia: Barriers Identified in a Qualitative Study.

BACKGROUND: The lack of early detection in breast cancer management has been identified as the primary factor contributing to the high mortality rate. The introduction of BPJS Kesehatan, Indonesia's national health insurance, was intended to ensure the provision of adequate health services for breast cancer patients. This study aimed to investigate the current state of health services in Indonesia concerning the early detection of breast cancer, following the implementation of BPJS Kesehatan introduction. METHODS: The study was conducted in 2017 in Yogyakarta, Indonesia. Subjects were recruited using a purposive sampling technique with maximum variation. The sample comprised breast cancer patients, health care professionals (HCPs), and healthy women from the general population with no history of breast cancer. The subjects' experiences and knowledge of health services regarding the early detection of breast cancer were investigated through in-depth interviews. Thematic analysis was used to synthesize the results from interviews with 25 participants. RESULT: This study identified several issues that hinder the timely detection of breast cancer. The lack of both screening and diagnostic procedures emerged as a prominent obstacle in breast cancer management. The study identified the following barriers: (1) limited community knowledge about early detection; (2). lack of urgency among patients to seek medical treatment; (3) limited access to health facilities; and (4) inconsistent adherence among health care professionals to guidelines for both screening and diagnostic procedures. CONCLUSIONS: This study revealed multiple factors contributing to the delay in breast cancer detection in Indonesia, leading to suboptimal management of the disease. It is crucial for the government to prioritize the improvement of enabling factors across all levels of care for early detection. These factors include initiatives to increase public awareness, improve access to health services, strengthen the referral system, and enhance health facilities.

Pralsetinib for RET Fusion-Positive Advanced Non-small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Roche) of pralsetinib (Gavreto®), as part of the single technology appraisal (STA) process, to submit evidence for the clinical effectiveness and cost effectiveness of pralsetinib for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small-cell lung cancer (NSCLC) not previously treated with a RET inhibitor. Kleijnen Systematic Reviews Ltd, in collaboration with University Medical Center Groningen, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarizes the company submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS reported data from the ARROW trial. ARROW is a single-arm, multicenter, non-randomized, open-label, multi-cohort study in patients with RET fusion-positive NSCLC and other advanced solid tumors. The CS included both untreated and pre-treated RET fusion-positive NSCLC patients, among other disease types. The comparators in the untreated population were pembrolizumab + pemetrexed + chemotherapy and pembrolizumab monotherapy. The comparators for the pre-treated population were docetaxel monotherapy, docetaxel + nintedanib, and platinum-based chemotherapy ± pemetrexed. As no comparators were included in ARROW, an indirect treatment comparison was conducted to estimate relative effectiveness. The ERG's concerns included the immaturity of data, small sample size, and lack of comparative safety evidence. The ERG considers the clinical evidence presented to be insufficiently robust to inform the economic model. Even when all the ERG preferred assumptions were implemented in the model, uncertainty remained on a number of issues, such as the appropriateness of the hazard ratios and the methods and data used to derive them, long-term efficacy of pralsetinib, and direct evidence for health-related quality of life (HRQoL). NICE did not recommend pralsetinib within its marketing authorization for treating RET fusion-positive advanced non-small-cell lung cancer (NSCLC) in adults who have not had a RET inhibitor before. The uncertainty of the clinical evidence and the estimates of cost effectiveness were too high to be considered a cost-effective use of NHS resources. Therefore, pralsetinib was not recommended for routine use.

Filgotinib for Treating Moderately to Severely Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited the manufacturer (Galapagos) of filgotinib (Jyseleca®), as part of the Single Technology Appraisal process, to submit evidence for the clinical effectiveness and cost effectiveness of filgotinib for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, loss of response or were intolerant to a previous biologic agent or conventional therapy. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group. This paper summarises the company submission, presents the Evidence Review Group's critical review on the clinical and cost-effectiveness evidence in the company submission, highlights the key methodological considerations and describes the development of the National Institute for Health and Care Excellence guidance by the Appraisal Committee. The company submission included one relevant study for the comparison of filgotinib versus placebo: the SELECTION trial. As there was no head-to-head evidence with any of the comparators, the company performed two separate network meta-analyses, one for the biologic-naïve population and one for the biologic-experienced population, and for both the induction and maintenance phases. The Evidence Review Group questioned the validity of the maintenance network meta-analysis because it assumed all active treatments to be comparators in this phase, which is not in line with clinical practice. The economic analysis used a number of assumptions that introduced substantial uncertainty, which could not be fully explored, for instance, the assumption that a risk of loss of response would be independent of health state and constant over time. Company and Evidence Review Group results indicate that at its current price, and disregarding confidential discounts for comparators and subsequent treatments, filgotinib dominates some comparators (golimumab and adalimumab in the company base case, all but intravenous and subcutaneous vedolizumab in the Evidence Review Group's base case) in the biologic-naïve population. In the biologic-experienced population, filgotinib dominates all comparators in both the company and the Evidence Review Group's base case. Results should be interpreted with caution as some important uncertainties were not included in the modelling. These uncertainties were mostly centred around the maintenance network meta-analysis, loss of response, health-related quality-of-life estimates and modelling of dose escalation. The National Institute for Health and Care Excellence recommended filgotinib within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional or biological treatment cannot be tolerated, or if the disease has not responded well enough or has stopped responding to these treatments, and if the company provides filgotinib according to the commercial arrangement.

Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION.

BACKGROUND: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. METHODS: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. DISCUSSION: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for. TRIAL REGISTRATION: EudraCT 2021-005059-35 . Registered on 12 December 2021. Study Code TMP-2204-2021-47.

The Opportunity of Point-of-Care Diagnostics in General Practice: Modelling the Effects on Antimicrobial Resistance.

OBJECTIVES: Antimicrobial resistance (AMR) is a public health threat associated with antibiotic consumption. Community-acquired acute respiratory tract infections (CA-ARTIs) are a major driver of antibiotic consumption in primary care. We aimed to quantify the investments required for a large-scale rollout of point-of care (POC) diagnostic testing in Dutch primary care, and the impact on AMR due to reduced use of antibiotics. METHODS: We developed an individual-based model that simulates consultations for CA-ARTI at GP practices in the Netherlands and compared a scenario where GPs test all CA-ARTI patients with a hypothetical diagnostic strategy to continuing the current standard-of-care for the years 2020-2030. We estimated differences in costs and future AMR rates caused by testing all patients consulting for CA-ARTI with a hypothetical diagnostic strategy, compared to the current standard-of-care in GP practices. RESULTS: Compared to the current standard-of-care, the diagnostic algorithm increases the total costs of GP consultations for CA-ARTI by 9% and 19%, when priced at €5 and €10, respectively. The forecast increase in Streptococcus pneumoniae resistance against penicillins can be partly restrained by the hypothetical diagnostic strategy from 3.8 to 3.5% in 2030, albeit with considerable uncertainty. CONCLUSIONS: Our results show that implementing a hypothetical diagnostic strategy for all CA-ARTI patients in primary care raises the costs of consultations, while lowering antibiotic consumption and AMR. Novel health-economic methods to assess and communicate the potential benefits related to AMR may be required for interventions with limited gains for individual patients, but considerable potential related to antibiotic consumption and AMR.

Early cost-effectiveness analysis of screening for preeclampsia in nulliparous women: A modelling approach in European high-income settings.

BACKGROUND: Preeclampsia causes substantial maternal and perinatal morbidity and mortality and significant societal economic impact. Effective screening would facilitate timely and appropriate prevention and management of preeclampsia. OBJECTIVES: To develop an early cost-effectiveness analysis to assess both costs and health outcomes of a new screening test for preeclampsia from a healthcare payer perspective, in the United Kingdom (UK), Ireland, the Netherlands and Sweden. METHODS: A decision tree over a 9-month time horizon was developed to explore the cost-effectiveness of the new screening test for preeclampsia compared to the current screening strategy. The new test strategy is being developed so that it can stratify healthy low risk nulliparous women early in pregnancy to either a high-risk group with a risk of 1 in 6 or more of developing preeclampsia, or a low-risk group with a risk of 1 in 100 or less. The model simulated 25 plausible scenarios in a hypothetical cohort of 100,000 pregnant women, in which the sensitivity and specificity of the new test were varied to set a benchmark for the minimum test performance that is needed for the test to become cost-effective. The input parameters and costs were mainly derived from published literature. The main outcome was incremental costs per preeclampsia case averted, expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Base case results showed that the new test strategy would be more effective and less costly compared to the current situation in the UK. In the Netherlands, the majority of scenarios would be cost-effective from a threshold of €50,000 per preeclampsia case averted, while in Ireland and Sweden, the vast majority of scenarios would be considered cost-effective only when a threshold of €100,000 was used. In the best case analyses, ICERs were more favourable in all four participating countries. Aspirin effectiveness, prevalence of preeclampsia, accuracy of the new screening test and cost of regular antenatal care were identified as driving factors for the cost-effectiveness of screening for preeclampsia. CONCLUSION: The results indicate that the new screening test for preeclampsia has potential to be cost-effective. Further studies based on proven accuracy of the test will confirm whether the new screening test is a cost-effective additional option to the current situation.

Impact of personality functioning and pathological traits on mental wellbeing of older patients with personality disorders.

BACKGROUND: Although personality disorders are common and consequential, they are largely ignored in geriatric mental healthcare. We examined the relative contributions of different aspects of personality disorders and comorbid mental disorders to the impairment of mental wellbeing in older adults. METHODS: Baseline data were used of 138 patients who participated in a randomized controlled trial on schema therapy for geriatric mental health outpatients with a full or subthreshold cluster B or C personality disorder. Personality was assessed according to both the categorical and dimensional model of DSM-5. Aspects of mental wellbeing assessed were; psychological distress, positive mental health, subjective health, and life satisfaction. The current study uses baseline data of the RCT to examine the associations between different aspects of personality pathology and mental wellbeing by multivariate regression analysis, controlling for age, sex, level of education, and number of chronic somatic illnesses. RESULTS: The vast majority of patients (79.0%) had one or more mental disorders in addition to personality disorder. Personality pathology was responsible for the core of the mental health burden experienced by patients, and negated the influence of co-occurring mental disorders when entered subsequently in multivariate analysis. Personality dimensions proved to be highly predictive of mental wellbeing, and this contrasted with absence of influence of personality disorder diagnosis. Although the personality functioning dimensions - and in particular Identity integration (large effect size with partial eta-squared = 0.36) - were the primary predictors of mental wellbeing, personality trait dimensions added significant predictive value to that (Disinhibition 0.25 and Negative affect 0.24). CONCLUSIONS: Personality disorders seriously affect the mental wellbeing of patients, and this overshadows the impact of comorbid mental disorders. In particular personality functioning and pathological traits of the Alternative Model of Personality Disorders (AMPD) of DSM-5 contribute to this impact on mental wellbeing. Alertness for and treatment of personality disorders in geriatric mental healthcare seems warranted.

Health-Economic Analyses of Diagnostics: Guidance on Design and Reporting.

Cost-effectiveness analyses (CEAs) can be used to assess the value of diagnostics in clinical practice. Due to the introduction of the European in vitro diagnostic and medical devices regulations, more clinical data on new diagnostics may become available, which may improve the interest and feasibility of performing CEAs. We present eight recommendations on the reporting and design of CEAs of diagnostics. The symptoms patients experience, the clinical setting, locations of test sampling and analysis, and diagnostic algorithms should be clearly reported. The used time horizon should reflect the time horizon used to model the treatment after the diagnostic pathway. Quality-adjusted life-years (QALYs) or disability-adjusted life-years (DALYs) should be used as the clinical outcomes but may be combined with other relevant outcomes, such as real options value. If the number of tests using the same equipment can vary, the economy of scale should be considered. An understandable graphical representation of the various diagnostic algorithms should be provided to understand the results, such as an efficiency frontier. Finally, the budget impact and affordability should be considered. These recommendations can be used in addition to other, more general, recommendations, such as the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) or the reference case for economic evaluation by the international decision support initiative.

Economic Analyses of Respiratory Tract Infection Diagnostics: A Systematic Review.

BACKGROUND: Diagnostic testing for respiratory tract infections is a tool to manage the current COVID-19 pandemic, as well as the rising incidence of antimicrobial resistance. At the same time, new European regulations for market entry of in vitro diagnostics, in the form of the in vitro diagnostic regulation, may lead to more clinical evidence supporting health-economic analyses. OBJECTIVE: The objective of this systematic review was to review the methods used in economic evaluations of applied diagnostic techniques, for all patients seeking care for infectious diseases of the respiratory tract (such as pneumonia, pulmonary tuberculosis, influenza, sinusitis, pharyngitis, sore throats and general respiratory tract infections). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles from three large databases of scientific literature were included (Scopus, Web of Science and PubMed) for the period January 2000 to May 2020. RESULTS: A total of 70 economic analyses are included, most of which use decision tree modelling for diagnostic testing for respiratory tract infections in the community-care setting. Many studies do not incorporate a generally comparable clinical outcome in their cost-effectiveness analysis: fewer than half the studies (33/70) used generalisable outcomes such as quality-adjusted life-years. Other papers consider outcomes related to the accuracy of the test or outcomes related to the prescribed treatment. The time horizons of the studies generally are limited. CONCLUSIONS: The methods to economically assess diagnostic tests for respiratory tract infections vary and would benefit from clear recommendations from policy makers on the assessed time horizon and outcomes used.

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 11C-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 11C-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's κ. 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/Ncortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A κ 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, 11C-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.

Efficiency of Diagnostic Testing for Helicobacter pylori Infections-A Systematic Review.

BACKGROUND: The most recommended treatment for a Helicobacter pylori infection is high doses of combined antibiotics. The objective of this article is to perform a systematic review of the economic evaluation studies applied to assess the efficiency of diagnostic testing for H. pylori infections, so that their main characteristics can be identified and to learn from the literature how the antimicrobial resistance (AMR) issue is incorporated into these economic evaluations. METHODS: We conducted a systematic review to compare the costs and clinical effectiveness of diagnostic strategies for H. pylori infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and extracted the items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: We found thirteen articles that were of good quality according to CHEERS: six studies focused on diagnostics of Helicobacter pylori infections associated with dyspepsia and four on duodenal ulcers. Testing was found to be the most cost-effective strategy in eight articles. Four studies considered AMR. CONCLUSIONS: Testing was more cost-effective than empirical treatment, except in cases of high prevalence (as with developing countries) or when patients could be stratified according to their comorbidities. The introduction of AMR into the model may change the efficiency of the testing strategy.

Diagnostic Testing for Sepsis: A Systematic Review of Economic Evaluations.

INTRODUCTION: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies. MATERIAL AND METHODS: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts. RESULTS: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens). CONCLUSION: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients.

Knowledge and Acceptance Towards Mammography as Breast Cancer Screening Tool Among Yogyakarta Women and Health Care Providers (Mammography Screening in Indonesia).

Annual mammography remains the gold standard of asymptomatic breast cancer screening for women starting at the age of 40. However, Indonesia has not designated mammography as its national screening program. To help policymakers decide whether mammography should be introduced into a national program, it is important to comprehensively understand the knowledge and acceptance of both consumers and providers. A total of 25 subjects including a range of women and health care professionals (HCPs) in Yogyakarta Province were recruited using purposive, maximum variation sampling and then interviewed in-depth. The interviews were recorded and all data were taken and transcribed from the audio recording, which were subsequently translated to English and analyzed thematically. Almost all of Yogyakarta women had heard about the term of mammography. However, only few of them have let themselves be screened, mainly because of their perceived lack of urgency to screen for asymptomatic breast cancer. Another important reason was the high cost of mammography. Meanwhile, several HCPs believed that breast cancer has not been a priority for the government and hence the government limited mammography screening's access and excluded it from the national insurance coverage. Most women in Yogyakarta have a good understanding about breast cancer screening, but their acceptance of mammography as a breast cancer screening tool is significantly influenced by high cost, limited access, and lack of urgency.

Lenalidomide with Rituximab for Previously Treated Follicular Lymphoma and Marginal Zone Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of lenalidomide (Revlimid®), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of lenalidomide in combination with rituximab (MabThera®), together referred to as R2, for the treatment of adults with treated follicular lymphoma (FL) or marginal zone lymphoma (MZL). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS included one relevant study, for the comparison of R2 versus rituximab monotherapy (R-mono): the AUGMENT trial. In addition, the company performed an unanchored indirect comparison of R2 versus rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and rituximab combined with cyclophosphamide, vincristine, and prednisolone (R-CVP), using data for R2 from the AUGMENT trial and pooled data for R-CHOP/R-CVP from the Haematological Malignancy Research Network (HMRN) database. During the STA process, the company provided an addendum containing evidence on only the FL population, in line with the marketing authorisation obtained at that time, which did not include MZL. The probabilistic incremental cost-effectiveness ratios (ICERs) presented by the company were £27,768 per quality-adjusted life year (QALY) gained for R2 versus R-CHOP, £41,602 per QALY gained for R2 versus R-CVP, and £23,412 per QALY gained for R2 versus R-mono. The ERG's concerns included the validity of the unanchored comparison, the unavailability of a state transition model to verify the outcomes of the partitioned survival model, substantial uncertainty in survival curves, and potential over-estimation of utility values. The revised ERG base case resulted in ICERs ranging from £16,874 to £44,888 per QALY gained for R2 versus R-CHOP, from £23,135 to £59,810 per QALY gained for R2 versus R-CVP, and from £18,779 to £27,156 per QALY gained for R2 versus R-mono. Substantial uncertainty remained around these ranges. NICE recommended R2 within its marketing authorisation, as an option for previously treated FL (grade 1-3A) in adults, contingent on the company providing lenalidomide according to the commercial arrangement.