Validating Health Economic Models With the Probabilistic Analysis Check dashBOARD.

OBJECTIVES: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making. This study aimed to develop and test a generic dashboard to systematically explore the workings of HE models and validate their model parameters and outcomes. METHODS: The Probabilistic Analysis Check dashBOARD (PACBOARD) was developed using insights from literature, health economists, and a data scientist. Functionalities of PACBOARD are (1) exploring and validating model parameters and outcomes using standardized validation tests and interactive plots, (2) visualizing and investigating the relationship between model parameters and outcomes using metamodeling, and (3) predicting HE outcomes using the fitted metamodel. To test PACBOARD, 2 mock HE models were developed, and errors were introduced in these models, eg, negative costs inputs, utility values exceeding 1. PACBOARD metamodeling predictions of incremental net monetary benefit were validated against the original model's outcomes. RESULTS: PACBOARD automatically identified all errors introduced in the erroneous HE models. Metamodel predictions were accurate compared with the original model outcomes. CONCLUSIONS: PACBOARD is a unique dashboard aiming at improving the feasibility and transparency of validation efforts of HE models. PACBOARD allows users to explore the working of HE models using metamodeling based on HE models' parameters and outcomes.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNFi in JIA patients. METHODS: Retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were either immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalisation) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9,165/patient on active treatment (pre-withdrawal) and decreased significantly to €5,063/patient (-44.8%) and €6,569/patient (-28.3%) in the first and second year post-withdrawal, respectively (p< 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1,180/patient, and €1,320/patient, in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first, and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs are decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdraw decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

Determining the Comparative Value of Pharmaceutical Risk-Sharing Policies in Non-Small Cell Lung Cancer Using Real-World Data.

BACKGROUND: Risk-sharing arrangements (RSAs) can be used to mitigate uncertainty about the value of a drug by sharing the financial risk between payer and pharmaceutical company. We evaluated the projected impact of alternative RSAs for non-small cell lung cancer (NSCLC) therapies based on real-world data. METHODS: Data on treatment patterns of Dutch NSCLC patients from four different hospitals were used to perform "what-if" analyses, evaluating the costs and benefits likely associated with various RSAs. In the scenarios, drug costs or refunds were based on response evaluation criteria in solid tumors (RECIST) response, survival compared to the pivotal trial, treatment duration, or a fixed cost per patient. Analyses were done for erlotinib, gemcitabine/cisplatin, and pemetrexed/platinum for metastatic NSCLC, and gemcitabine/cisplatin, pemetrexed/cisplatin, and vinorelbine/cisplatin for nonmetastatic NSCLC. RESULTS: Money-back guarantees led to moderate cost reductions to the payer. For conditional treatment continuation schemes, costs and outcomes associated with the different treatments were dispersed. When price was linked to the outcome, the payer's drug costs reduced by 2.5% to 26.7%. Discounted treatment initiation schemes yielded large cost reductions. Utilization caps mainly reduced the costs of erlotinib treatment (by 16%). Given a fixed cost per patient based on projected average use of the drug, risk sharing was unfavorable to the payer because of the lower than projected use. The impact of RSAs on a national scale was dispersed. CONCLUSIONS: For erlotinib and pemetrexed/platinum, large cost reductions were observed with risk sharing. RSAs can mitigate uncertainty around the incremental cost-effectiveness or budget impact of drugs, but only when the type of arrangement matches the setting and type of uncertainty.

Balancing the Optimal and the Feasible: A Practical Guide for Setting Up Patient Registries for the Collection of Real-World Data for Health Care Decision Making Based on Dutch Experiences.

OBJECTIVES: The aim of this article was to provide practical guidance in setting up patient registries to facilitate real-world data collection for health care decision making. METHODS: This guidance was based on our experiences and involvement in setting up patient registries in oncology in the Netherlands. All aspects were structured according to 1) mission and goals ("the Why"), 2) stakeholders and funding ("the Who"), 3) type and content ("the What"), and 4) identification and recruitment of patients, data handling, and pharmacovigilance ("the How"). RESULTS: The mission of most patient registries is improving patient health by improving the quality of patient care; monitoring and evaluating patient care is often the primary goal ("the Why"). It is important to align the objectives of the registry and agree on a clear and functional governance structure with all stakeholders ("the Who"). There is often a trade off between reliability, validity, and specificity of data elements and feasibility of data collection ("the What"). Patient privacy should be carefully protected, and address (inter-)national and local regulations. Patient registries can reveal unique safety information, but it can be challenging to comply with pharmacovigilance guidelines ("the How"). CONCLUSIONS: It is crucial to set up an efficient patient registry that serves its aims by collecting the right data of the right patient in the right way. It can be expected that patient registries will become the new standard alongside randomized controlled trials due to their unique value.

Treatments and costs for recurrent and/or metastatic squamous cell carcinoma of the head and neck in the Netherlands.

For patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), chemotherapy can prolong life and alleviate symptoms. However, expected gains may be small, not necessarily outweighing considerable toxicity and high costs. Treatment choice is to a large extent dependent on preferences of doctors and patients and data on these choices are scarce. The purpose of this study is to obtain real-world information on palliative systemic treatment and costs of R/M SCCHN in the Netherlands. In six Dutch head and neck treatment centers, data were collected on patient and tumor characteristics, treatment patterns, disease progression, survival, adverse events, and resource use for R/M SCCHN, between 2006 and 2013. 125 (14 %) out of 893 R/M SCCHN patients received palliative, non-trial first-line systemic treatment, mainly platinum + 5FU + cetuximab (32 %), other platinum-based combination therapy (13 %), methotrexate monotherapy (27 %) and capecitabine monotherapy (14 %). Median progression-free survival and overall survival were 3.4 and 6.0 months, respectively. 34 (27 %) patients experienced severe adverse events. Mean total hospital costs ranged from € 10,075 (± € 9,891) (methotrexate monotherapy) to € 39,459 (± € 21,149) (platinum + 5FU + cetuximab). Primary cost drivers were hospital stays and anticancer drug treatments. Major health care utilization and costs are involved in systemically treating R/M SCCHN patients with a limited survival.

Cetuximab in locally advanced squamous cell carcinoma of the head and neck: generalizability of EMR 062202-006 trial results.

In a randomized controlled trial in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), treatment with RT plus cetuximab resulted in improved survival compared to treatment with RT alone. Uncertainty exists about the generalizability of the trial results for the Dutch healthcare setting due to possible discrepancies in treatment allocation. Retrospective patient chart review was performed for 141 patients treated with first line RT plus cetuximab or RT alone, diagnosed in 2007-2010 in two head and neck treatment centers. Combined with aggregated population-based data from the Netherlands Cancer Registry and patient level clinical trial data, use of cetuximab in Dutch daily practice was assessed through comparison of patient characteristics, treatment characteristics and treatment outcomes between trial and daily practice. 61 daily practice patients fulfilled the selection criteria. In line with Dutch guidelines, RT plus cetuximab is prescribed in patients requiring combined therapy unfit to receive traditional platinum-based chemotherapeutics. These patients have unfavorable baseline characteristics, due to selection on--amongst others--high age of the patients. Beyond 1 year after treatment start, patients treated with RT plus cetuximab in daily practice died earlier than patients treated with RT plus cetuximab in the trial. Selective treatment allocation in daily practice limits generalizability of EMR 062202-006 trial results. Evidence is needed about the effectiveness of RT plus cetuximab compared to other treatments for patients with unfavorable clinical baseline characteristics.

Evaluation of a flexible acute admission unit: effects on transfers to other hospitals and patient throughput times.

INTRODUCTION: To prevent overcrowding of the emergency department, a flexible acute admission unit (FAAU) was created, consisting of 15 inpatient regular beds located in different departments. We expected the FAAU to result in fewer transfers to other hospitals and in a lower length of stay (LOS) of patients needing hospital admission. METHODS: A before-and-after interventional study was performed in a level 1 trauma center in the Netherlands. Number of transfers and LOS of admitted ED patients in a 4-month period in 2008 (control period) and a 4-month period in 2009 (intervention period) were analyzed. RESULTS: Of 1,619 regular admission patients, 768 were admitted in the control period and 851 in the intervention period. The number of transfers decreased from 80 (10.42%) to 54 (6.35%) (P = .0037). The mean ED LOS of both the non-admitted patients and the admitted patients needing special care significantly increased (105 minutes vs 117 minutes [P = .022] and 176 minutes vs 191 minutes [P < .001], respectively). However, the mean LOS of FAAU-admissible patients was unaltered (226 minutes vs 225 minutes, P = .865). CONCLUSIONS: The FAAU reduced the number of transfers of admitted patients to other hospitals. The increase in LOS for special care patients and non-admitted patients was not observed for regular, FAAU-admissible patients. Flexible bed management might be useful in preventing overcrowding.

Effects of process changes on emergency department crowding in a changing world: an interrupted time-series analysis.

BACKGROUND: During a 6-year period, several process changes were introduced at the emergency department (ED) to decrease crowding, such as the implementation of a general practitioner cooperative (GPC) and additional medical staff during peak hours. In this study, we assessed the effects of these process changes on three crowding measures: patients' length of stay (LOS), the modified National ED OverCrowding Score (mNEDOCS), and exit block while taking into account changing external circumstances, such as the COVID-19 pandemic and centralization of acute care. METHODS: We determined time points of the various interventions and external circumstances and built an interrupted time-series (ITS) model per outcome measure. We analyzed changes in level and trend before and after the selected time points using ARIMA modeling, to account for autocorrelation in the outcome measures. RESULTS: Longer patients' ED LOS was associated with more inpatient admissions and more urgent patients. The mNEDOCS decreased with the integration of the GPC and the expansion of the ED to 34 beds and increased with the closure of a neighboring ED and ICU. More exit blocks occurred when more patients with shortness of breath and more patients > 70 years of age presented to the ED. During the severe influenza wave of 2018-2019, patients' ED LOS and the number of exit blocks increased. CONCLUSIONS: In the ongoing battle against ED crowding, it is pivotal to understand the effect of interventions, corrected for changing circumstances and patient and visit characteristics. In our ED, interventions which were associated with decreased crowding measures included the expansion of the ED with more beds and the integration of the GPC on the ED.

The impact of prehospital blood sampling on the emergency department process of patients with chest pain: a pragmatic non-randomized controlled trial.

BACKGROUND: In patients with chest pain who arrive at the emergency department (ED) by ambulance, venous access is frequently established prehospital, and could be utilized to sample blood. Prehospital blood sampling may save time in the diagnostic process. In this study, the association of prehospital blood draw with blood sample arrival times, troponin turnaround times, and ED length of stay (LOS), number of blood sample mix-ups and blood sample quality were assessed. METHODS: The study was conducted from October 1, 2019 to February 29, 2020. In patients who were transported to the ED with acute chest pain with low suspicion for acute coronary syndrome (ACS), outcomes were compared between cases, in whom prehospital blood draw was performed, and controls, in whom blood was drawn at the ED. Regression analyses were used to assess the association of prehospital blood draw with the time intervals. RESULTS: Prehospital blood draw was performed in 100 patients. In 406 patients, blood draw was performed at the ED. Prehospital blood draw was independently associated with shorter blood sample arrival times, shorter troponin turnaround times and decreased LOS (P<0.001). No differences in the number of blood sample mix-ups and quality were observed (P>0.05). CONCLUSION: For patients with acute chest pain with low suspicion for ACS, prehospital blood sampling is associated with shorter time intervals, while there were no significant differences between the two groups in the validity of the blood samples.

Association between Covid-19 surge and emergency department patient flow and experience.

BACKGROUND: Preparations for Covid-19 in the Netherlands included hospital reconfigurations to increase capacity for the expected surge at the emergency department (ED). We describe patients' ED length of stay (LOS), crowding and experiences of patients with respiratory complaints during the first Covid-19 peak. METHODS: Retrospective analysis of demand, ED LOS, crowding, and a patient experience survey during a 12-week period in 2020 and similar periods in 2018 and 2019. Crowding levels were calculated using the National ED OverCrowding Scale. RESULTS: The number of patients with respiratory complaints increased significantly, while total ED numbers were unchanged. Although presentation during the Covid-19 peak and needing hospital admission were associated with a longer ED LOS in patients with respiratory complaints, significantly less crowding occurred compared with the 2018 and 2019 periods. Increased ED LOS was associated with lower patient experience scores. CONCLUSION: Advanced warning and its associated preparation within the hospital and the community prevented significant delays in ED throughput during the first Covid-19 peak.

Health care cost of crusted scabies in Aboriginal communities in the Northern Territory, Australia.

BACKGROUND: Crusted scabies is a debilitating dermatological condition. Although still relatively rare in the urban areas of Australia, rates of crusted scabies in remote Aboriginal communities in the Northern Territory (NT) are reported to be among the highest in the world. OBJECTIVE: To estimate the health system costs associated with diagnosing, treating and managing crusted scabies. METHODS: A disease pathway model was developed to identify the major phases of managing crusted scabies. In recognition of the higher resource use required to treat more severe cases, the pathway differentiates between crusted scabies severity grades. The disease pathway model was populated with data from a clinical audit of 42 crusted scabies patients diagnosed in the Top-End of Australia's Northern Territory between July 1, 2016 and May 1, 2018. These data were combined with standard Australian unit costs to calculate the expected costs per patient over a 12-month period, as well as the overall population cost for treating crusted scabies. FINDINGS: The expected health care cost per patient diagnosed with crusted scabies is $35,418 Australian dollars (AUD) (95% CI: $27,000 to $43,800), resulting in an overall cost of $1,558,392AUD (95% CI: $1,188,000 to $1,927,200) for managing all patients diagnosed in the Northern Territory in a given year (2018). By far, the biggest component of the health care costs falls on the hospital system. DISCUSSION: This is the first cost-of-illness analysis for treating crusted scabies. Such analysis will be of value to policy makers and researchers by informing future evaluations of crusted scabies prevention programs and resource allocation decisions. Further research is needed on the wider costs of crusted scabies including non-financial impacts such as the loss in quality of life as well as the burden of care and loss of well-being for patients, families and communities.

Refining a triage system for use in emergency departments.

This article reports on the implementation of an adapted version of the Manchester triage system (Mackway-Jones et al 1997) in a Dutch hospital to allow trained nurse practitioners to treat patients with minor injuries or illnesses, and to assess, treat and discharge patients autonomously. The project has helped to prevent long waits in emergency departments for patients with less urgent conditions.

Impact of ongoing centralization of acute stroke care from "drip and ship" into "direct-to-mothership" model in a Dutch urban area.

When acute stroke care is organised using a "drip-and-ship" model, patients receive immediate treatment at the nearest primary stroke centre followed by transfer to a comprehensive stroke centre (CSC). When stroke care is further centralised into the "direct-to-mothership" model, patients with stroke symptoms are immediately brought to a CSC to further reduce treatment times and enhance stroke outcomes. We investigated the effects of the ongoing centralization in a Dutch urban setting on treatment times of patients with confirmed ischemic stroke in a 4-year period. Next, in a non-randomized controlled trial, we assessed treatment times of patients with suspected ischemic stroke, and treatment times of patients with neurologic disorders other than suspected ischemic stroke, before and after the intervention in the CSC and the decentralized hospitals, the intervention being the change from "drip and ship" into "direct-to-mothership". Our findings provide support for the ongoing centralization of acute stroke care in urban areas. Treatment times for patients with ischemic stroke decreased significantly, potentially improving functional outcomes. Improvements in treatment times for patients with suspected ischemic stroke were achieved without negative side effects for self-referrals with stroke symptoms and patients with other neurological disorders.

Perceptions of a 'virtual' acute admission unit.

The Haaglanden Medical Centre, the Hague, Netherlands, has opened a 'virtual' acute admission unit (VAAU) to increase throughput of acute patients. The VAAU consists of 15 inpatient beds located on different wards that are set aside for patients from the emergency department (ED) when all of the beds on specialty wards are being used. A qualitative evaluation of the VAAU has revealed that it has reduced emergency nurses' workload and allowed them more time to see and treat patients. This suggests that the introduction of VAAUs may address similar problems of ED throughput in the U.K.

Night-time confusion in an elderly woman post-stroke.

For patients with acute ischaemic stroke, faster recanalisation improves the chances of a disability-free life and a quick discharge from the hospital. Hospital discharge, certainly after suffering a major life-changing event such as a stroke, is a complex and vulnerable phase in the patient's journey. Elderly are particularly vulnerable to the stressors caused by hospitalisation. Recently hospitalised patients are not only recovering from their acute illness; they also experience a period of generalised risk for a range of adverse events. At the same time, elderly generally prefer living in their own homes and should be discharged from the hospital and return home as quickly as possible. Both premature and delayed discharge are potential threats to patient well-being. We present a 90-year-old patient who underwent successful thrombectomy but suffered from night-time confusion at the hospital and discuss the transition process from hospital to home.

Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study.

OBJECTIVES: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. MATERIALS AND METHODS: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. RESULTS: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. CONCLUSION: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations.

Why is There Discordance between the Reimbursement of High-Cost 'Life-Extending' Pharmaceuticals and Medical Devices? The Funding of Ventricular Assist Devices in Australia.

New health technologies often yield health benefits, but often at a high cost. In Australia, the processes for public reimbursement of high-cost pharmaceuticals and medical devices are different, potentially resulting in inequity in support for new therapies. We explore how reimbursement is different for medical devices compared with pharmaceuticals, including whether higher cost-effectiveness thresholds are accepted for pharmaceuticals. A literature review identified the challenges of economic evaluations for medical devices compared with pharmaceuticals. We used the ventricular assist device as a case study to highlight specific features of medical device funding in Australia. We used existing guidelines to evaluate whether ventricular assist devices would fulfil the requirements for the "Life-Saving Drugs Program", which is usually reserved for expensive life-extending pharmaceutical treatments of serious and rare medical conditions. The challenges in conducting economic evaluations of medical devices include limited data to support effectiveness, device-operator interaction (surgical experience) and incremental innovations (miniaturisation). However, whilst high-cost pharmaceuticals may be funded by a single source (federal government), the funding of high-cost devices is complex and may be funded via a combination of federal, state and private health insurance. Based on the Life-Saving Drugs Program criteria, we found that ventricular assist devices could be funded by a similar mechanism to that which funds high-cost life-extending pharmaceuticals. This article highlights the complexities of medical device reimbursement. Whilst differences in available evidence affect the evaluation process, differences in funding methods contribute to inequitable reimbursement decisions between medical devices and pharmaceuticals.

Real-World Cost Effectiveness of Mandatory Folic Acid Fortification of Bread-Making Flour in Australia.

BACKGROUND: In 2009, mandatory folic acid fortification of bread-making flour was introduced in Australia to reduce the birth prevalence of preventable neural tube defects (NTDs) such as spina bifida. Before the introduction of the policy, modelling predicted a reduction of 14-49 NTDs each year. OBJECTIVE: Using real-world data, this study provides the first ex-post evaluation of the cost effectiveness of mandatory folic acid fortification of bread-making flour in Australia. METHODS: We developed a decision tree model to compare different fortification strategies and used registry data to quantify the change in NTD rates due to the policy. We adopted a societal perspective that included costs to industry and government as well as healthcare and broader societal costs. RESULTS: We found 32 fewer NTDs per year in the post-mandatory folic acid fortification period. Mandatory folic acid fortification improved health outcomes and was highly cost effective because of the low intervention cost. The policy demonstrated improved equity in outcomes, particularly in birth prevalence of NTDs in births from teenage and indigenous mothers. CONCLUSIONS: This study calculated the value of mandatory folic acid fortification using real-world registry data and demonstrated that the attained benefit was comparable to the modelled expected benefits. Mandatory folic acid fortification (in addition to policies including advice on supplementation and education) improved equity in certain populations and was effective and highly cost effective for the Australian population.

A systematic review of scabies transmission models and data to evaluate the cost-effectiveness of scabies interventions.

BACKGROUND: Scabies is a common dermatological condition, affecting more than 130 million people at any time. To evaluate and/or predict the effectiveness and cost-effectiveness of scabies interventions, disease transmission modelling can be used. OBJECTIVE: To review published scabies models and data to inform the design of a comprehensive scabies transmission modelling framework to evaluate the cost-effectiveness of scabies interventions. METHODS: Systematic literature search in PubMed, Medline, Embase, CINAHL, and the Cochrane Library identified scabies studies published since the year 2000. Selected papers included modelling studies and studies on the life cycle of scabies mites, patient quality of life and resource use. Reference lists of reviews were used to identify any papers missed through the search strategy. Strengths and limitations of identified scabies models were evaluated and used to design a modelling framework. Potential model inputs were identified and discussed. FINDINGS: Four scabies models were published: a Markov decision tree, two compartmental models, and an agent-based, network-dependent Monte Carlo model. None of the models specifically addressed crusted scabies, which is associated with high morbidity, mortality, and increased transmission. There is a lack of reliable, comprehensive information about scabies biology and the impact this disease has on patients and society. DISCUSSION: Clinicians and health economists working in the field of scabies are encouraged to use the current review to inform disease transmission modelling and economic evaluations on interventions against scabies.