Cost-utility analysis of Dexcom G6 real-time continuous glucose monitoring versus FreeStyle Libre 1 intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in Belgium.

AIMS/HYPOTHESIS: The aim of this study was to assess the long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring (rtCGM) with alert functionality compared with FreeStyle Libre 1 intermittently scanned continuous glucose monitoring (isCGM) without alerts in adults with type 1 diabetes in Belgium. METHODS: The IQVIA CORE Diabetes Model was used to estimate cost-effectiveness. Input data for the simulated baseline cohort were sourced from the randomised ALERTT1 trial (ClinicalTrials.gov. REGISTRATION NO: NCT03772600). The age of the participants was 42.9 ± 14.1 years (mean ± SD), and the baseline HbA1c was 57.8 ± 9.5 mmol/mol (7.4 ± 0.9%). Participants using rtCGM showed a reduction in HbA1c of 3.6 mmol/mol (0.36 percentage points) based on the 6-month mean between-group difference. In the base case, both rtCGM and isCGM were priced at €3.92/day (excluding value-added tax [VAT]) according to the Belgian reimbursement system. The analysis was performed from a Belgian healthcare payer perspective over a lifetime time horizon. Health outcomes were expressed as quality-adjusted life years. Probabilistic and one-way sensitivity analyses were used to account for parameter uncertainty. RESULTS: In the base case, rtCGM dominated isCGM, resulting in lower diabetes-related complication costs and better health outcomes. The associated main drivers favouring rtCGM were lower HbA1c, fewer severe hypoglycaemic events and reduced fear of hypoglycaemia. The results were robust under a wide range of one-way sensitivity analyses. In models where the price of rtCGM is €5.11/day (a price increase of 30.4%) or €12.34/day (a price increase of 214.8%), rtCGM was cost-neutral or reached an incremental cost-effectiveness ratio of €40,000 per quality-adjusted life year, respectively. CONCLUSIONS/INTERPRETATION: When priced similarly, Dexcom G6 rtCGM with alert functionality has both economic and clinical benefits compared with FreeStyle Libre 1 isCGM without alerts in adults with type 1 diabetes in Belgium, and appears to be a cost-effective glucose monitoring modality. Trial registration ClinicalTrials.gov NCT03772600.

Implementation and evaluation of a multi-level mental health promotion intervention for the workplace (MENTUPP): study protocol for a cluster randomised controlled trial.

BACKGROUND: Well-organised and managed workplaces can be a source of wellbeing. The construction, healthcare and information and communication technology sectors are characterised by work-related stressors (e.g. high workloads, tight deadlines) which are associated with poorer mental health and wellbeing. The MENTUPP intervention is a flexibly delivered, multi-level approach to supporting small- and medium-sized enterprises (SMEs) in creating mentally healthy workplaces. The online intervention is tailored to each sector and designed to support employees and leaders dealing with mental health difficulties (e.g. stress), clinical level anxiety and depression, and combatting mental health-related stigma. This paper presents the protocol for the cluster randomised controlled trial (cRCT) of the MENTUPP intervention in eight European countries and Australia. METHODS: Each intervention country will aim to recruit at least two SMEs in each of the three sectors. The design of the cRCT is based on the experiences of a pilot study and guided by a Theory of Change process that describes how the intervention is assumed to work. SMEs will be randomly assigned to the intervention or control conditions. The aim of the cRCT is to assess whether the MENTUPP intervention is effective in improving mental health and wellbeing (primary outcome) and reducing stigma, depression and suicidal behaviour (secondary outcome) in employees. The study will also involve a process and economic evaluation. CONCLUSIONS: At present, there is no known multi-level, tailored, flexible and accessible workplace-based intervention for the prevention of non-clinical and clinical symptoms of depression, anxiety and burnout, and the promotion of mental wellbeing. The results of this study will provide a comprehensive overview of the implementation and effectiveness of such an intervention in a variety of contexts, languages and cultures leading to the overall goal of delivering an evidence-based intervention for mental health in the workplace. TRIAL REGISTRATION: Please refer to Item 2a and registration ISRCTN14104664. Registered on 12th July 2022.

Economic Evaluation of Medically Assisted Reproduction: A Methodological Systematic Review.

BACKGROUND: Medically assisted reproduction (MAR) is a challenging application area for health economic evaluations, entailing a broad range of costs and outcomes, stretching out long-term and accruing to several parties. PURPOSE: To systematically review which costs and outcomes are included in published economic evaluations of MAR and to compare these with health technology assessment (HTA) prescriptions about which cost and outcomes should be considered for different evaluation objectives. DATA SOURCES: HTA guidelines and systematic searches of PubMed Central, Embase, WOS CC, CINAHL, Cochrane (CENTRAL), HTA, and NHS EED. STUDY SELECTION: All economic evaluations of MAR published from 2010 to 2022. DATA EXTRACTION: A predetermined data collection form summarized study characteristics. Essential costs and outcomes of MAR were listed based on HTA and treatment guidelines for different evaluation objectives. For each study, included costs and outcomes were reviewed. DATA SYNTHESIS: The review identified 93 cost-effectiveness estimates, of which 57% were expressed as cost-per-(healthy)-live-birth, 19% as cost-per-pregnancy, and 47% adopted a clinic perspective. Few adopted societal perspectives and only 2% used quality-adjusted life-years (QALYs). Broader evaluations omitted various relevant costs and outcomes related to MAR. There are several cost and outcome categories for which available HTA guidelines do not provide conclusive directions regarding inclusion or exclusion. LIMITATIONS: Studies published before 2010 and of interventions not clearly labeled as MAR were excluded. We focus on methods rather than which MAR treatments are cost-effective. CONCLUSIONS: Economic evaluations of MAR typically calculate a short-term cost-per-live-birth from a clinic perspective. Broader analyses, using cost-per-QALY or BCRs from societal perspectives, considering the full scope of reproduction-related costs and outcomes, are scarce and often incomplete. We provide a summary of costs and outcomes for future research guidance and identify areas requiring HTA methodological development. HIGHLIGHTS: The cost-effectiveness of MAR procedures can be exceptionally complex to estimate as there is a broad range of costs and outcomes involved, in principle stretching out over multiple generations and over many stakeholders.We list 21 key areas of costs and outcomes of MAR. Which of these needs to be accounted for alters for different evaluation objectives (determined by the type of economic evaluation, time horizon considered, and perspective).Published studies mostly investigate cost-effectiveness in the very short-term, from a clinic perspective, expressed as cost-per-live-birth. There is a lack of comprehensive economic evaluations that adopt a broader perspective with a longer time horizon. The broader the evaluation objective, the more relevant costs and outcomes were excluded.For several costs and outcomes, particularly those relevant for broader, societal evaluations of MAR, the inclusion or exclusion is theoretically ambiguous, and HTA guidelines do not offer sufficient guidance.

Public health impact and return on investment of Belgium's pediatric immunization program.

Objective: We evaluated the public health impact and return on investment of Belgium's pediatric immunization program (PIP) from both healthcare-sector and societal perspectives. Methods: We developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0-10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre-vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit-cost ratio. Scenario analyses considered alternate assumptions for key model inputs. Results: Across all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium's PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs. Conclusion: Belgium's PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact.

The value of treatment for infertility: A systematic literature review of willingness-to-pay thresholds and approaches for determining the cost effectiveness of fertility therapies.

Willingness to pay (WTP) for an infertility treatment is the maximum amount of money a patient is willing to pay per treatment, or to achieve a live birth or pregnancy. Such thresholds are important to determine the cost effectiveness of a treatment. A systematic review was conducted to identify and explore the studies that attempt to ascertain WTP for infertility and compare them with the cost-effectiveness studies that claimed to use WTP thresholds. For comparison, all the costs were converted and inflated to 2021 euros. The results demonstrated that there were no standard outcomes or WTP thresholds for an outcome/treatment, and the methodologies used vary. Cost-effectiveness studies either used the incremental cost-effectiveness ratio to imply a WTP threshold, or used thresholds that were previously accepted for a quality-adjusted life year outcome converted, inappropriately, to an infertility outcome. There is a need for further research by health economists to develop a consensus for the meaningful assessment of WTP for ART.

Cost-effectiveness of point-of-care interventions to tackle inappropriate prescribing of antibiotics in high- and middle-income countries: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is propagated by widespread inappropriate use of antibiotics. In response, point-of-care interventions (POCIs) have been developed in primary care to preserve antibiotic effectiveness. Many of these POCIs are adopted based on their clinical value. However, assessment of their cost-effectiveness is crucial as well. OBJECTIVES: To summarize the evidence on cost-effectiveness of POCIs aimed at tackling inappropriate antibiotic prescriptions in primary care in middle- and high-income countries. We also evaluate the quality of the evidence with particular attention to how these economic evaluations faced the challenge of capturing the impact of these POCIs on AMR. METHODS: Six scientific databases (MEDLINE, Embase, Web of Science, NHS EED, NHS HTA, the Cochrane Library) were searched for eligible articles published from 1999 to 2022. Their quality was appraised by means of the Drummond and CHEERS checklist. RESULTS: Twenty-nine articles met the selection criteria. Using their own (implicit) definitions of cost-effectiveness, evidence reported that point-of-care testing, scoring tools, electronic interventions, communication training, and multidimensional and educational interventions are more cost-effective than standard care. In contrast, studies found dipstick testing and audit-and-feedback interventions to be not cost-effective. Data synthesis took a narrative approach as eligible studies were not similar and/or reliable enough to pool their results through meta-analysis. CONCLUSIONS: More high-quality evidence is needed to attain a thorough understanding of the cost-effectiveness of POCIs. Heterogeneity in terms of interventions and efficiency measures complicates comparing and generalizing results. Methodological recommendations are urgently needed to economically evaluate POCIs, focusing on how AMR should be accounted for.

Accounting for Adverse Events Following Immunization in Economic Evaluation: Systematic Review of Economic Evaluations of Pediatric Vaccines Against Pneumococcus, Rotavirus, Human Papillomavirus, Meningococcus and Measles-Mumps-Rubella-Varicella.

OBJECTIVES: Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events following immunization (AEFI). We investigated to what extent economic evaluations of pediatric vaccines account for AEFI, which methods are used to do so and whether inclusion of AEFI is associated with study characteristics and the vaccine's safety profile. METHODS: A systematic literature search (MEDLINE, EMBASE, Cochrane Systematic Reviews and Trials, Database of the Centre for Reviews and Dissemination of the University of York, EconPapers, Paediatric Economic Database Evaluation, Tufts New England Cost-Effectiveness Analysis Registry, Tufts New England Global Health CEA, International Network of Agencies for Health Technology Assessment Database) was performed for economic evaluations published between 2014 and 29 April 2021 (date of search) pertaining to the five groups of pediatric vaccines licensed in Europe and the United States since 1998: the human papillomavirus (HPV) vaccines, the meningococcal vaccines (MCV), the measles-mumps-rubella-varicella (MMRV) combination vaccines, the pneumococcal conjugate vaccines (PCV) and the rotavirus vaccines (RV). Rates of accounting for AEFI were calculated, stratified by study characteristics (e.g., region, publication year, journal impact factor, level of industry involvement) and triangulated with the vaccine's safety profile (Advisory Committee on Immunization Practices [ACIP] recommendations and information on safety-related product label changes). The studies accounting for AEFI were analyzed in terms of the methods used to account for both cost and effect implications of AEFI. RESULTS: We identified 112 economic evaluations, of which 28 (25%) accounted for AEFI. This proportion was significantly higher for MMRV (80%, four out of five evaluations), MCV (61%, 11 out of 18 evaluations) and RV (60%, nine out of 15 evaluations) compared to HPV (6%, three out of 53 evaluations) and PCV (5%, one out of 21 evaluations). No other study characteristics were associated with a study's likelihood of accounting for AEFI. Vaccines for which AEFI were more frequently accounted for also had a higher frequency of label changes and a higher level of attention to AEFI in ACIP recommendations. Nine studies accounted for both the cost and health implications of AEFI, 18 studies considered only costs and one only health outcomes. While the cost impact was usually estimated based on routine billing data, the adverse health impact of AEFI was usually estimated based on assumptions. DISCUSSION: Although (mild) AEFI were demonstrated for all five studied vaccines, only a quarter of reviewed studies accounted for these, mostly in an incomplete and inaccurate manner. We provide guidance on which methods to use to better quantify the impact of AEFI on both costs and health outcomes. Policymakers should be aware that the impact of AEFI on cost-effectiveness is likely to be underestimated in the majority of economic evaluations.

Stability of Stated Preferences: Vaccine Priority Setting before and during the First COVID-19 Lockdown.

BACKGROUND: Discrete choice experiments (DCEs) are frequently used to study preferences and quantify tradeoffs in decision making. It is important to understand how stable their results are. OBJECTIVE: To investigate to what extent an extreme change in context, the COVID-19 pandemic, affected preferences for vaccine priority setting, as observed in an earlier DCE. METHODS: We replicated a DCE in which participants had to prioritize vaccination programs for public funding. The initial DCE was executed in Flanders (Belgium) right before the onset of the SARS-CoV-2 pandemic (December 2019, N = 1,636). The replicated DCE was executed 6 months later when the population was in lockdown (April 2020, N = 1,127). A total of 612 respondents participated in both waves of the DCE. We used panel mixed logit models to quantify attribute and level importance and compared utility estimates for consistency. RESULTS: The number of vaccine-preventable deaths became less important during the pandemic than before, whereas the influential attributes, the vaccine's contribution to disease eradication and certainty about vaccine effectiveness became even more important. Respondents attached equal importance to the number of patients with transient or permanent morbidity, to the disease's economic impact as well as to its equity profile. CONCLUSION: Different preferences for vaccine priority setting were observed during the first COVID-19 lockdown as compared with before, although these differences were, given the extreme nature of the changing circumstances, relatively small. HIGHLIGHTS: We replicated a discrete choice experiment (DCE) about vaccine priority setting during the first COVID-19 lockdown and compared results with those from the original setting.The major attributes, contribution to disease eradication, and scientific certainty about vaccine effectiveness became even more important than they already were, whereas avoidable mortality became less important.Respondents attached equal importance to the number of patients with transient or permanent morbidity, to the disease's economic impact as well as to its equity profile.An extreme change in directly related context to the choice assignment led to changes in stated preferences, although these changes were relatively small, given the extreme change in context.Priorities in the second DCE were even less aligned with cost-effectiveness analysis than those observed initially.

Healthcare costs of post-traumatic trigeminal neuropathy in Belgium - A retrospective analysis.

The present aim was to estimate direct health care costs of patients suffering from post-traumatic trigeminal neuropathy (PTTN) and to compare the use of health care services, medications, and costs between temporary and persistent (>3 months) PTTN cohorts. A pre-existing clinical dataset of PTTN patients visiting a tertiary orofacial pain clinic in Belgium was utilized, including symptoms and quality of life measurements. Cost and resource utilization data were obtained by Belgium's largest health insurance provider for a period of 5 years after onset. Data from 158 patients was analyzed. The average cost per patient in the first year after injury was €2353 (IQR 1426-4499) with an out-of-pocket expense of 25% of the total cost. Hospitalization and technical interventions were the main drivers of cumulative costs, followed by consultation costs. For each cost category, expenditure was significantly higher in patients with persistent PTTN than in those with temporary PTTN (median 5-year total costs in persistent PTTN patients yielded €8866 (IQR 4368-18191) versus €4432 (IQR 2156-9032) in temporary PTTN, p <0.001) PTTN patients received repeated and frequent head and neck imaging (mean number of imaging investigations per patient was 10 ± 12). Medication consumption was high, with an unwarranted higher use of opioids and antibiotics in persistent PTTN patients. Within the limitations of this study, it seems there is a need for informing patients in detail on the inherent risks of nerve damage during dental and oromaxillofacial procedures. Every surgery should be preceded by a risk-benefit assessment in order to avoid unnecessary nerve damage.

The effect of a trAnSitional Pharmacist Intervention in geRiatric inpatients on hospital visits after dischargE (ASPIRE): Protocol for a randomized controlled trial.

BACKGROUND: Unplanned rehospitalizations occur frequently in older patients. Drug-related problems constitute a major and largely preventable cause with inappropriate prescribing being a substantial culprit. Solutions are needed to reduce this risk by targeting pharmacotherapy both during and after hospital stay. Therefore, we aim to perform a randomized controlled trial in geriatric inpatients to investigate the impact of a multifaceted clinical pharmacy intervention on health-related outcomes. METHODS/DESIGN: The study concerns a monocenter, non-blinded, randomized controlled trial that will take place at the acute geriatric wards of a large academic hospital. Patients being in a palliative stage with active therapy withdrawal or patients discharged to another ward within the same hospital or another hospital are excluded. In total, 828 patients will be randomized (1:1) to the usual care or intervention group. The multifaceted clinical pharmacy intervention comprises medication reconciliation at admission and discharge, medication review, patient/caregiver education, intensified communication with primary care providers and post-discharge follow-up, which also includes a telepharmacology service. The primary endpoint is defined as the time to an all-cause, unplanned hospital revisit within six months after discharge. Other health-related outcomes such as drug-related readmissions, quality of life and number of potentially inappropriate medications will be analyzed as secondary endpoints. Patient inclusion started in February 2021. DISCUSSION: This study will provide useful insights regarding the impact of clinical pharmacy interventions on geriatric wards with the goal to optimize health-related outcomes such as hospital revisits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617340.

Social preferences for adopting new vaccines in the national immunization program: A discrete choice experiment.

Governments regularly have to decide whether new vaccines should be adopted in their national immunization program. These choices imply complex trade-offs of epidemiological, medical and socio-economic criteria. We investigated how the population in Flanders (Belgium) wants their government to set vaccine-funding priorities. In December 2019, we executed a discrete choice experiment in a sample of the Flemish population (N = 1636). In total, we analysed 16 360 choices between vaccines competing for funding, described in terms of eight characteristics. Using a panel mixed logit model, we quantified the relative importance of each characteristic and investigated differences in preferences across respondent groups. The observed vaccine priorities were different from those that would be identified through cost-effectiveness analysis. People valued the health impact from infectious diseases differently than their weight expressed in QALYs would suggest. Mortality and frequently occurring mild illness were valued higher, whereas lasting morbidity received lower weight. Contribution of the vaccine to disease eradication and uncertainty in vaccine effectiveness were both highly influential factors. Health equity impact was also important whereas the economic impact of the disease did not matter at all. Our results can be used to incorporate public values into vaccine decision-making.

Cost-effectiveness of mental health interventions during and after pregnancy: A systematic review.

BACKGROUND: Mental health problems during and after pregnancy such as depression, anxiety, post-traumatic stress disorder (PTSD), or addiction are common and can have lifelong implications for both parents and offspring. This review investigates the cost-effectiveness of interventions tackling these problems, assesses the methodological quality of included studies, and indicates suggestions for further research. METHODS: Thirteen databases were searched for economic evaluations of interventions related to antenatal, perinatal, and postnatal mental health conditions, published between 2000 and September 2021, in high-income countries. RESULTS: Thirty-nine studies met all inclusion criteria. Interventions considered were screening programs, pharmacological treatments, and various forms of psychosocial and psychological support. Six studies reported that the intervention was cost-saving. Eighteen were cost-effective and seven likely to be cost-effective. Only six studies included health outcomes for the child; one study considered paternal health. The time horizon for which costs and consequences were considered was for most evaluations limited to 1 year (n = 18) or 2 years (n = 11) postpartum. CONCLUSIONS: Given the importance of the subject, a relatively low number of studies have investigated the cost-effectiveness of interventions tackling mental health problems during and after pregnancy. The scant evidence available suggests good overall value for money. Likely, cost-effectiveness is underestimated as costly long-term consequences on offspring are systematically excluded. No evidence was found for several frequently occurring conditions. Further research is required to obtain reliable, long-term effectiveness data and to address the methodological challenges related to measuring all relevant health outcomes for all parties affected.

Economic evaluation of Medically Assisted Reproduction: An educational overview of methods and applications for healthcare professionals.

Economic evaluations of the value-for-money of Medically Assisted Reproduction (MAR) interventions are increasingly important due to growing pressure on healthcare budgets. Although such evaluations are commonplace in the published literature, the number/methodological complexity of different evaluations available, and the challenges specific to MAR interventions, can complicate the interpretation of such analyses for fertility treatments. This article aims to serve as an educational resource and provide context on the design/interpretation of economic analyses for MAR interventions. Several areas are relevant for first-line providers and decision makers: scope of analysis, comparator used, perspective/time horizon considered, outcomes used to measure success, and how results from cost-effectiveness studies can be summarised and used in clinical practice. We aim to help clinicians better understand the strengths/weaknesses of economic analyses, to enable the best use of the evidence in practice, so resources available for MAR interventions can provide maximum value to patients and society.

Short-term effectiveness of face-to-face periodic occupational health screening versus electronic screening with targeted follow-up: results from a quasi-randomized controlled trial in four Belgian hospitals.

OBJECTIVES: In many countries, organisations are legally obliged to have occupational physicians screen employees regularly. However, this system is time-intensive, and there may be more cost-effective alternatives. Our objective is to compare the short-term effectiveness of periodic occupational health screening of hospital employees by an occupational physician with a system of electronic screening with targeted follow-up. METHODS: A randomized controlled trial was set up among personnel of four Belgian hospitals, with three measurement moments between June 2019 and December 2020, to compare differences in self-assessed health, healthcare use, productivity and intermediate outcomes over 19 months. Mixed effects models were used to assess differences in effectiveness. Superiority and non-inferiority post-hoc tests were used as a robustness check. The experiment coincided with the first two COVID-19 waves during which hospital employees were exposed to an exceptional period of occupational stress. RESULTS: In total, 1077 employees (34% of the target population) participated. Although we observed some immediate effects of the intervention (less trust in the physician, absenteeism, and healthcare use), all these effects disappeared over time. After 19 months, including two waves of COVID-19 hospitalizations, no significant differences were observed between employees screened through face-to-face contact and those screened electronically. CONCLUSIONS: Our study finds no indication that, in the short-term, substituting physician screening of the workforce with a quicker survey-based screening with targeted follow-up has different effects on the studied endpoints. However, as health and disease are often the result of a long-term process, more evidence is needed to determine long-term effects.

Cost-effectiveness of check of medication appropriateness: methodological approach.

Background Adverse drug events following inappropriate prescribing in the hospital cause a substantial and avoidable medical and economic burden to hospitals, payers and patients alike. A clinical rule-based, pharmacist-led medication-review service, the 'Check of Medication Appropriateness' (CMA) was implemented in the University Hospitals Leuven. The CMA is shown to be effective in reducing potentially inappropriate prescriptions. Aim This study investigated whether this centralised clinical pharmacy service is cost-effective. Method We performed a cost-effectiveness analysis of three clinical rules of the CMA, targeting adverse drug events at three levels of severity: A) persistent opioid-induced constipation, B) ketorolac-induced gastrointestinal bleeding and C) drug-induced Torsade de Pointes. A decision tree was developed for each clinical rule. Both intervention costs as well as total costs associated with the occurrence of an adverse drug event were considered. The outcomes were reported in the form of an incremental cost-effectiveness ratio, expressed as an incremental cost per adverse drug event avoided. Results Applying clinical rules to avoid persistent opioid-induced constipation and ketorolac-induced gastrointestinal bleeding were cost-saving. Implementation of a medication check to avoid drug-induced Torsade de Pointes costed €8,846 per Torsade de Pointes avoided. Conclusion Our study provides strong indications that the CMA is worth its investment for clinical rules targeting (very) common adverse drug events, that can be avoided with limited expenses. Further research is required to assess the full CMA. The proposed model may be useful to perform cost-effectiveness analyses of other centralised clinical pharmacy services targeting inappropriate prescribing, at the level of individual adverse drug events.

Antibiotic prescribing rate after optimal near-patient C-reactive protein testing in acutely ill children presenting to ambulatory care (ARON project): protocol for a cluster-randomized pragmatic trial.

INTRODUCTION: Children become ill quite often, mainly because of infections, most of which can be managed in the community. Many children are prescribed antibiotics which contributes to antimicrobial resistance and reinforces health-seeking behaviour. Point-of-care C reactive protein (POC CRP) testing, prescription guidance and safety-netting advice can help safely reduce antibiotic prescribing to acutely ill children in ambulatory care as well as save costs at a systems level. METHODS AND ANALYSIS: The ARON (Antibiotic prescribing Rate after Optimal Near-patient testing in acutely ill children in ambulatory care) trial is a pragmatic cluster randomized controlled superiority trial with a nested process evaluation and will assess the clinical and cost effectiveness of a diagnostic algorithm, which includes a standardised clinical assessment, a POC CRP test, and safety-netting advice, in acutely ill children aged 6 months to 12 years presenting to ambulatory care. The primary outcome is antibiotic prescribing at the index consultation; secondary outcomes include clinical recovery, reconsultation, referral/admission to hospital, additional testing, mortality and patient satisfaction. We aim to recruit a total sample size of 6111 patients. All outcomes will be analysed according to the intent-to-treat approach. We will use a mixed-effect logistic regression analysis to account for the clustering at practice level. ETHICS AND DISSEMINATION: The study will be conducted in compliance with the principles of the Declaration of Helsinki (current version), the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements. Ethics approval for this study was obtained on 10 November 2020 from the Ethics Committee Research of University Hospitals Leuven under reference S62005. We will ensure that the findings of the study will be disseminated to relevant stakeholders other than the scientific world including the public, healthcare providers and policy-makers. The process evaluation that is part of this trial may provide a basis for an implementation strategy. If our intervention proves to be clinically and cost-effective, it will be essential to educate physicians about introducing the diagnostic algorithm including POC CRP testing and safety-netting advice in their daily practice. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470518. Protocol V.2.0 date 2 October 2020. (Pre-results).

Future Offspring Costs in Economic Evaluation.

Economic evaluation guidelines increasingly prescribe inclusion of all future costs. We point at an important dimension of future costs that is systematically neglected. Healthcare can affect future offspring, either through affecting the patient's fertility or through determining future offspring's health. As we show, the future costs associated with these changes can be substantial and will vary across interventions and demographic groups. However, systematic inclusion of these future offspring costs would raise many problems on its own. Based on the population ethics concept of necessitarianism, we suggest that only those future costs that spring from 'necessary' future lives should be included in future cost calculations, while all costs associated with 'potential' future lives can be ignored. This approach allows excluding most future offspring costs and avoids skewed cost-effectiveness outcomes of interventions with fertility effects, while taking into account the economic implications of preventing disease in future generations that will exist by necessity. Overall, future generations expose a substantial gap in today's Health Technology Assessment (HTA) methodology and further discussion of the issues they raise is needed.

Belgium's response to the COVID-19 pandemic.

Belgium is often seen as an outlier in the international experience with the coronavirus disease 2019. We summarize the unfolding of the pandemic in Belgium from February to December 2020, discuss the countermeasures that were implemented and provide some explanations why the numbers indicate a stronger pandemic in Belgium than in its neighbouring countries. To some extent, the seemingly poor performance of Belgium is a measurement artefact. Yet, there were indeed particular factors in Belgium that unnecessarily increased the toll of the pandemic. In the first wave insufficient priority was given to protect care homes. The second wave was larger than necessary due to a failure to timely implement restrictive measures. The latter can, at least partly, be explained by a unique political situation: a temporary, minority government in the middle of a major crisis.