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.

A cost analysis of a simplified model for HCV screening and treatment at a tertiary hospital in Zimbabwe.

BACKGROUND: The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe. METHODS: We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care. RESULTS: The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care. CONCLUSION: Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Cost-effectiveness model of trastuzumab deruxtecan as second-line treatment in HER2-positive unresectable and/or metastatic breast cancer in Finland.

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland. METHODS: A three-state partitioned survival analysis model was developed with a payer's perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly-for progression-free survival and time to treatment discontinuation-or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data-for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model. RESULTS: Total quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were €106,800, resulting in an ICER of €55,360 per QALY gained and an ICER of €41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case. CONCLUSIONS: T-DXd is cost-effective based on surrogate WTP thresholds of €72,000 and €139,000 per QALY.

The right time to measure anti-Xa activity in critical illness: pharmacokinetics of therapeutic dose nadroparin.

Background: Peak anti-Xa activity of low-molecular-weight heparin nadroparin is measured 3 to 5 hours after subcutaneous injection. In critically ill patients, physiological changes and medical therapies may result in peak activities before or after this interval, possibly impacting dosing. Objectives: The primary objective was to determine the percentage of critically ill patients with adequately estimated peak activities drawn 3 to 5 hours after subcutaneous administration of a therapeutic dose of nadroparin. Adequate was defined as a peak activity of ≥80% of the actual peak anti-Xa activity. If ≥80% of patients had adequately estimated peak activities in the 3- to 5-hour interval, measurement in this interval was regarded as acceptable. The secondary objective was to determine the pharmacokinetic profile of nadroparin. Methods: In this single-center, prospective study, we evaluated anti-Xa activities in patients admitted to a general intensive care unit. After ≥4 equal doses of nadroparin, anti-Xa activity was measured according to a 12- to 24-hour sampling scheme. Results: In 25 patients, anti-Xa activities drawn between 3 and 5 hours after administration ranged 80% to 100% of the actual peak activity. Compared to the threshold level of an adequate estimation in at least 20 patients (≥80%), measuring anti-Xa activities in the 3- to 5-hour interval is an acceptable method (1-tailed binomial test; P < .02). We found a large interindividual variability for nadroparin exposure (mean ± SD area-under-the-curve0-12h, 10.3 ± 4.8 IU·h/mL) and delayed elimination (t1/2 range, 4.0-120.9 hours) despite adequate renal function. Conclusion: In critically ill patients, measuring anti-Xa activity in a 3- to 5-hour interval after subcutaneous injection of therapeutic nadroparin is an acceptable method to estimate the actual peak anti-Xa activity.

Adherence to protocols for the use of reversal agents in patients treated with direct oral anticoagulants.

OBJECTIVES: This study aimed to evaluate the adherence to protocols for the use of reversal agents in direct oral anticoagulant (DOAC) users in Dutch hospitals. METHODS: A retrospective cohort study was conducted in seven hospitals in the Netherlands. Treatment protocols for bleeding and (urgent) procedures in patients on DOAC were collected from each hospital. All patient data on the use of reversal agents were retrospectively collected from September 2021 to April 2022 and compared to the protocols. The degree of per-protocol adherence (compliance score) was categorized into four levels as follows: poor (<45%), moderate (45-79%), high (80-89%), and full (> 90%) adherence rates. RESULTS: A total of 290 patients were included in our study. In patients with bleeding under DOAC, the protocol adherence for prothrombin complex concentrate (PCC) was "moderate" (61%). In the remaining cases (39%), non-adherence was mainly caused by underdosing (68%), overdosing (12%), and a lack of indication (14%). Furthermore, idarucizumab was administered for bleeding with "full" adherence (96%). For andexanet alfa, adherence to the hospital bleeding protocol was "moderate" (67%), with a lack of indication being the only reason for non-adherence. In case of reversal for an urgent procedure, the protocol adherence for PCC was "low" (45%), with underdosing, a lack of indication, and missing lab data being the main reasons for non-adherence. Missing lab data on dabigatran plasma concentration before reversal was the main reason for "low" adherence (26%) in idarucizumab. The adherence for andexanet alfa was also "low" (0%). CONCLUSION: In case of reversal for bleeding under DOAC, overall adherence to the protocol was "moderate"; however, in patients needing an urgent procedure, it was "low." The major reasons for non-adherence were underdosing, off-label use, and a lack of specific lab testing. The results of this study can assist in improving the implementation of hospital protocols.

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands.

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands. METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.

Correction: Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings.

[This corrects the article DOI: 10.1371/journal.pone.0222658.].

Cost-effectiveness analysis of quadrivalent and nonavalent human papillomavirus vaccines in Ethiopia.

BACKGROUND: In Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia. METHOD: A static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered. RESULTS: At a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita. CONCLUSION: Compared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15.

Cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands in different age groups.

OBJECTIVE: We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. METHODS: A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. RESULTS: The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50-60 years, 50-70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50-60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60-70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50-60 years and 50-70 years. CONCLUSION: This study showed that lung cancer screening is cost-effective in the Netherlands.

Progress on the elimination of viral hepatitis in Zimbabwe: A review of the policies, strategies and challenges.

Very few low-income countries have developed national plans to achieve the viral hepatitis elimination targets set in the World Health Organization (WHO) strategy. We reviewed the policy environment, strategies and challenges on the fight against viral hepatitis in Zimbabwe. The review focussed on the Ministry of Health and Child Care (MoHCC) policy documents, strategic plans and reports. We performed key informant interviews to enhance evidence generated from the document review. Twelve documents were reviewed and interviews with 10 key informants were completed. The MoHCC established a technical working group to work towards elimination of viral hepatitis. The technical working group drafted a strategic plan for elimination of viral hepatitis; however, it is still awaiting implementation. Key strategies that are working well include screening of donated blood for transfusion, safe injection practices and hepatitis B virus (HBV) three-dose vaccination. Current challenges in the drive towards elimination of viral hepatitis include poor to non-existent surveillance systems, lack of epidemiological data, absence of the HBV vaccine birth dose and lack of systematic screening and treatment services for viral hepatitis. In conclusion, despite political will demonstrated towards achieving viral hepatitis elimination, substantial investment and work are required to implement the strategic plan and realize significant success.

Persistent Socioeconomic Inequalities in Measles Vaccine Uptake in Ethiopia in the Period 2005 to 2016.

OBJECTIVE: This study aims to quantify socioeconomic inequalities-and the factors contributing to these inequalities-in measles vaccine uptake among children aged 12 to 23 months in Ethiopia between 2005 and 2016. METHODS: Inequalities in measles vaccine uptake were investigated based on data from the Ethiopian Demographic and Health Surveys conducted in 2005, 2011, and 2016. Concentration curves and concentration indices were used to measure the degree of inequality, and decomposition analysis was used to identify factors contributing to these inequalities. RESULTS: The overall level of national measles vaccine uptake in Ethiopia exhibited an increasing trend between 2005 and 2016. As indicated by the concentration index of measles vaccine uptake, however, which was estimated at 0.202 (P < .01) in 2005, 0.226 (P < .01) in 2011, and 0.223 (P < .01) in 2016, measles vaccine uptake became consistently more concentrated among children from more affluent households. The dominance test of the concentration curve further confirmed the persistence of inequalities in measles vaccine uptake over time. Various factors-including maternal educational level, antenatal care use, institutional delivery, and exposure to media-were identified as the most important contributors to the inequalities. CONCLUSIONS: Although the national measles vaccine uptake showed improvement between 2005 and 2016, socioeconomic inequalities in the uptake persisted over time. Efforts to improve the national immunization coverage should be accompanied by appropriate measures to address the inequalities.

Unintentional ingestion of a high dose of acenocoumarol in a young child.

Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L).

Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study.

OBJECTIVES: For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA. PATIENTS AND METHODS: In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed. CONCLUSIONS: A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding. TRIAL REGISTRATION NUMBER: NCT01431456.

Understanding the Improvement in Full Childhood Vaccination Coverage in Ethiopia Using Oaxaca-Blinder Decomposition Analysis.

In Ethiopia, full vaccination coverage among children aged 12-23 months has improved in recent decades. This study aimed to investigate drivers of the improvement in the vaccination coverage. The Oaxaca-Blinder decomposition technique was applied to identify the drivers using data from Ethiopian Demographic and Health Survey conducted in 2000 and 2016. The vaccination coverage rose from 14.3% in 2000 to 38.5% in 2016. The decomposition analysis showed that most of the rise in vaccination coverage (73.7%) resulted from the change in the effect of explanatory variables over time and other unmeasured characteristics. Muslim religion had a counteracting effect on the observed increase in vaccination coverage. The remaining 26.3% of the increase was attributed to the change in the composition of the explanatory variables between 2000 and 2016, with maternal educational level and maternal health care utilization as significant contributors. The findings highlight the need for further improvements in maternal health care utilization and educational status to maintain the momentum towards universal coverage of childhood vaccination. Targeted intervention among Muslim-dominated communities is also needed to improve the current situation. Besides which, future studies need to be conducted to identify additional potential modifiable factors.

The Cost-Effectiveness of Hepatitis C Virus Screening Strategies among Recently Arrived Migrants in the Netherlands.

OBJECTIVE: We aimed to assess the cost-effectiveness of hepatitis C virus (HCV) screening strategies among recently arrived migrants in the Netherlands. METHODS: A Markov model was used to estimate the health effects and costs of HCV screening from the healthcare perspective. A cohort of 50,000 recently arrived migrants was used. In this cohort, three HCV screening strategies were evaluated: (i) no screening, (ii) screening of migrants from HCV-endemic countries and (iii) screening of all migrants. RESULTS: Strategy (ii) screening of migrants from HCV-endemic countries compared to strategy (i) no screening, yielded an incremental cost-effectiveness ratio (ICER) of €971 per quality-adjusted life-years (QALYs) gained. Strategy (iii) screening of all migrants compared with strategy (ii) screening of migrants from HCV-endemic countries yielded an ICER of €1005 per QALY gained. The budget impact of strategy (ii) screening of migrants from HCV-endemic countries and strategy (iii) screening of all migrants was €13,752,039 and €20,786,683, respectively. CONCLUSION: HCV screening is cost-effective. However, the budget impact may have a strong influence on decision making.

Incidence, treatment and mortality of new-onset atrial fibrillation patients at the intensive care unit.

Objective: Critically ill patients admitted to the intensive care unit (ICU) often develop atrial fibrillation (AF), with an incidence of around 5%. Stroke prevention in AF is well described in clinical guidelines. The extent to which stroke prevention is prescribed to ICU patients with AF is unknown. We aimed to determine the incidence of new-onset AF and describe stroke prevention strategies initiated on the ICU of our teaching hospital. Also, we compared mortality in patients with new-onset AF to critically ill patients with previously diagnosed AF and patients without any AF. Methods: This study was a retrospective cohort study including all admissions to the ICU of the Martini Hospital (Groningen, The Netherlands) in the period 2011 to 2016. Survival analyses were performed using these real-world data. Results: In total, 3334 patients were admitted to the ICU, of whom 213 patients (6.4%) developed new-onset AF. 583 patients (17.5%) had a previous AF diagnosis, the other patients were in sinus rhythm. In-hospital mortality and 1-year mortality after hospital discharge were significantly higher for new-onset AF patients compared with patients with no history of AF or previously diagnosed AF. At hospital discharge, only 56.3% of the new-onset AF-patients eligible for stroke prevention received an anticoagulant. Anticoagulation was not dependent on CHA2DS2-VASc score or other patient characteristics. An effect of anticoagulative status on mortality was not significant. Conclusion: AF is associated with increased mortality in critically ill patients admitted to the ICU. More guidance is needed to optimise anticoagulant treatment in critically ill new-onset AF patients.

Inequalities in Rotavirus Vaccine Uptake in Ethiopia: A Decomposition Analysis.

A previous study in Ethiopia reported significant variation in rotavirus vaccine uptake across socioeconomic strata. This study aims to quantify socioeconomic inequality of rotavirus vaccine uptake in Ethiopia and to identify the contributing factors for the inequality. The concentration curve (CC) and the Erreygers Normalized Concentration Index (ECI) were used to assess the socioeconomic related inequality in rotavirus vaccine uptake using data from the 2016 Ethiopian Demographic and Health Survey. Decomposition analysis was conducted to identify the drivers of inequalities. The CC for rotavirus vaccine uptake lay below the line of equality and the ECI was 0.270 (p < 0.001) indicating that uptake of rotavirus vaccine in Ethiopia was significantly concentrated among children from families with better socioeconomic status. The decomposition analysis showed that underlining inequalities in maternal health care services utilization, including antenatal care use (18.4%) and institutional delivery (8.1%), exposure to media (12.8%), and maternal educational level (9.7%) were responsible for the majority of observed inequalities in the uptake of rotavirus vaccine. The findings suggested that there is significant socioeconomic inequality in rotavirus vaccine uptake in Ethiopia. Multi-sectoral actions are required to reduce the inequalities, inclusive increasing maternal health care services, and educational attainments among economically disadvantaged mothers.

Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings.

INTRODUCTION: Randomized clinical trials (RCTs) and real-world data (RWD) in patients with atrial fibrillation have shown that-compared to vitamin K antagonists (VKAs)-non-VKA oral anticoagulants (NOACs) are at least as effective in the prevention of ischaemic stroke, while decreasing the risk of bleeding. OBJECTIVE: We aim to evaluate the cost-effectiveness of the NOAC apixaban versus other NOACs (dabigatran, edoxaban and rivaroxaban) and VKA, for stroke prevention in patients with atrial fibrillation by including the available data both from RCT and real-world analyses of all NOACs into one integrative previously published model. METHODS: The model was updated to the current Dutch healthcare situation. The incremental cost-effectiveness ratio was calculated using either efficacy/effectiveness and safety data derived from a network meta-analysis (NMA) synthesizing NOAC RCTs or RWD. We conducted a systematic literature search to identify eligible publication to best inform the RWD-based analysis. Additional sensitivity and scenario analyses were conducted to test the robustness of the outcomes. RESULTS: In the NMA-based analysis, apixaban appeared to be cost-effective compared to VKA (€3,506 per quality adjusted life-year) and dominant (cost-saving and more effective) over dabigatran 110 mg, dabigatran 150 mg, edoxaban and rivaroxaban. In the RWD-based analysis, apixaban was dominant over all other anticoagulants. In the scenario analysis apixaban appeared to be not cost-effective compared to dabigatran 150 mg, when using equal event-unrelated treatment discontinuation rates for each drug. In all other scenarios apixaban is cost-effective or cost-saving compared to VKA and other NOACs. CONCLUSION: Based on RCTs as well as RWD, we conclude that apixaban is generally cost-effective or even cost-saving (less costly and more effective) compared to VKA and other NOACs in the overall population of patients with atrial fibrillation.

Pharmacotherapy within a learning healthcare system: rationale for the Dutch Santeon Farmadatabase.

OBJECTIVES: The increasing number of available, often expensive, medicines asks for continuous assessment of rational prescribing. We aimed to develop a simple and robust data infrastructure in order to monitor hospital medicine utilisation in real time. METHODS: Within a collaboration (Santeon) of large teaching hospitals in the Netherlands, we set up a process for extraction, transformation, anonymisation and load of individual medicine prescription data and major clinical outcomes from different hospital information systems into a central database. Quarterly reports were constructed to monitor and validate the quality of the uploaded data. RESULTS: A central database has been developed that includes data from all patients from 2010 onwards and is refreshed on a weekly basis by an automated process. Beginning in 2017, the database holds data from almost 800 000 patients with prescriptions. All hospitals provide at least 18 mandatory data items per patient. Provided data include, among others, individual prescriptions, diagnosis data, and hospitalisation and survival data. The database is currently used to benchmark the level of biosimilar prescribing and to assess the impact of novel systemic treatments on survival rates in metastatic cancers. CONCLUSION: We showed that it is feasible for a group of hospitals to construct their own database that can serve as a tool to benchmark the positioning of medicines and to start with monitoring their impact on clinical outcomes.