An approach to quantify parameter uncertainty in early assessment of novel health technologies.

Health economic modeling of novel technology at the early stages of a product lifecycle has been used to identify technologies that are likely to be cost-effective. Such early assessments are challenging due to the potentially limited amount of data. Modelers typically conduct uncertainty analyses to evaluate their effect on decision-relevant outcomes. Current approaches, however, are limited in their scope of application and imposes an unverifiable assumption, that is, uncertainty can be precisely represented by a probability distribution. In the absence of reliable data, an approach that uses the fewest number of assumptions is desirable. This study introduces a generalized approach for quantifying parameter uncertainty, that is, probability bound analysis (PBA), that does not require a precise specification of a probability distribution in the context of early-stage health economic modeling. We introduce the concept of a probability box (p-box) as a measure of uncertainty without necessitating a precise probability distribution. We provide formulas for a p-box given data on summary statistics of a parameter. We describe an approach to propagate p-boxes into a model and provide step-by-step guidance on how to implement PBA. We conduct a case and examine the differences between the status-quo and PBA approaches and their potential implications on decision-making.

Coverage with evidence development for medical devices in Europe: Can practice meet theory?

Health economists have written extensively on the design and implementation of coverage with evidence development (CED) schemes and have proposed theoretical frameworks based on cost-effectiveness modeling and value of information analysis. CED may aid decision-makers when there is uncertainty about the (cost-)effectiveness of a new health technology at the time of reimbursement. Medical devices are potential candidates for CED schemes, as regulatory regimes do not usually require the same level of efficacy and safety data normally needed for pharmaceuticals. The purpose of this research is to assess whether the actual practice of CED for medical devices in Europe meets the theoretical principles proposed by health economists and whether theory and practice can be more closely aligned. Based on decision-makers' perceptions of the challenges associated with CED schemes, plus examples from the schemes themselves, we discuss a series of proposals for assessing the desirability of schemes, their design, implementation, and evaluation. These proposals, while reflecting the practical challenges with developing CED programs, embody many of the principles suggested by economists and should support decision-makers in dealing with uncertainty about the real-world performance of devices.

The PMA Scale: A Measure of Physicians' Motivation to Adopt Medical Devices.

BACKGROUND: Studies have often stated that individual-level determinants are important drivers for the adoption of medical devices. Empirical evidence supporting this claim is, however, scarce. At the individual level, physicians' adoption motivation was often considered important in the context of adoption decisions, but a clear notion of its dimensions and corresponding measurement scales is not available. OBJECTIVES: To develop and subsequently validate a scale to measure the motivation to adopt medical devices of hospital-based physicians. METHODS: The development and validation of the physician-motivation-adoption (PMA) scale were based on a literature search, internal expert meetings, a pilot study with physicians, and a three-stage online survey. The data collected in the online survey were analyzed using exploratory factor analysis (EFA), and the PMA scale was revised according to the results. Confirmatory factor analysis (CFA) was conducted to test the results from the EFA in the third stage. Reliability and validity tests and subgroup analyses were also conducted. RESULTS: Overall, 457 questionnaires were completed by medical personnel of the National Health Service England. The EFA favored a six-factor solution to appropriately describe physicians' motivation. The CFA confirmed the results from the EFA. Our tests indicated good reliability and validity of the PMA scale. CONCLUSIONS: This is the first reliable and valid scale to measure physicians' adoption motivation. Future adoption studies assessing the individual level should include the PMA scale to obtain more information about the role of physicians' motivation in the broader adoption context.

The Role of Learning in Health Technology Assessments: An Empirical Assessment of Endovascular Aneurysm Repairs in German Hospitals.

Changes in performance due to learning may dynamically influence the results of a technology evaluation through the change in effectiveness and costs. In this study, we estimate the effect of learning using the example of two minimally invasive treatments of abdominal aortic aneurysms: endovascular aneurysm repair (EVAR) and fenestrated EVAR (fEVAR). The analysis is based on the administrative data of over 40,000 patients admitted with unruptured abdominal aortic aneurysm to more than 500 different hospitals over the years 2006 to 2013. We examine two patient outcomes, namely, in-hospital mortality and length of stay using hierarchical regression models with random effects at the hospital level. The estimated models control for patient and hospital characteristics and take learning interdependency between EVAR and fEVAR into account. In case of EVAR, we observe a significant decrease both in the in-hospital mortality and length of stay with experience accumulated at the hospital level; however, the learning curve for fEVAR in both outcomes is effectively flat. To foster the consideration of learning in health technology assessments of medical devices, a general framework for estimating learning effects is derived from the analysis. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

Preferred supplier contracts in post-patent prescription drug markets.

In recent years, the expiration of patents for large drug classes has increased the importance of post-patent drug markets. However, previous research has focused solely on patent drug markets. In this study, the authors evaluate the influence of preferred supplier contracts, the German approach to tendering, in post-patent drug markets using a hierarchical market share attraction model. The authors find that preferred supplier contracts are a powerful strategic instrument for generic manufacturers in a highly competitive environment. They quantify the effects of signing a preferred supplier contract and show that brand-name manufacturers are vulnerable to tendering. Therefore, brand-name manufacturers should readjust their strategies and consider including preferred supplier contracts in their marketing mix. In addition, the authors employ a simulation to demonstrate that a first-mover advantage might be gained from signing a preferred supplier contract. Furthermore, their results can be used as a blueprint for decision makers in the pharmaceutical industry to assess the market share effects of different contracting strategies regarding preferred supplier contracts.

Using nonparametric conditional approach to integrate quality into efficiency analysis: empirical evidence from cardiology departments.

Health care providers are under pressure to improve both efficiency and quality. The two objectives are not always mutually consistent, because achieving higher levels of quality may require additional resources. The aim of this study is to demonstrate how the nonparametric conditional approach can be used to integrate quality into the analysis of efficiency and to investigate the mechanisms through which quality enters the production process. Additionally, we explain how the conditional approach relates to other nonparametric methods that allow integrating quality into efficiency analysis and provide guidance on the selection of an appropriate methodology. We use data from 178 departments of interventional cardiology and consider three different measures of quality: patient satisfaction, standardized mortality ratio, and patient radiation exposure. Our results refute the existence of a clear trade-off between efficiency and quality. In fact, the impact of quality on the production process differs according to the utilized quality measure. Patient satisfaction does not affect the attainable frontier but does have an inverted U-shaped effect on the distribution of inefficiencies; mortality ratio negatively impacts the attainable frontier when the observed mortality more than doubles the predicted mortality; and patient radiation exposure is not associated with the production process.

Comparing the Efficiency of Hospitals in Italy and Germany: Nonparametric Conditional Approach Based on Partial Frontier.

Traditional nonparametric frontier techniques to measure hospital efficiency have been criticized for their deterministic nature and the inability to incorporate external factors into the analysis. Moreover, efficiency estimates represent a relative measure meaning that the implications from a hospital efficiency analysis based on a single-country dataset are limited by the availability of suitable benchmarks. Our first objective is to demonstrate the application of advanced nonparametric methods that overcome the limitations of the traditional nonparametric frontier techniques. Our second objective is to provide guidance on how an international comparison of hospital efficiency can be conducted using the example of two countries: Italy and Germany. We rely on a partial frontier of order-m to obtain efficiency estimates robust to outliers and extreme values. We use the conditional approach to incorporate hospital and regional characteristics into the estimation of efficiency. The obtained conditional efficiency estimates may deviate from the traditional unconditional efficiency estimates, which do not account for the potential influence of operational environment on the production possibilities. We nonparametrically regress the ratios of conditional to unconditional efficiency estimates to examine the relation of hospital and regional characteristics with the efficiency performance. We show that the two countries can be compared against a common frontier when the challenges of international data compatibility are successfully overcome. The results indicate that there are significant differences in the production possibilities of Italian and German hospitals. Moreover, hospital characteristics, particularly bed-size category, ownership status, and specialization, are significantly related to differences in efficiency performance across the analyzed hospitals.

Comparison of Site of Death, Health Care Utilization, and Hospital Expenditures for Patients Dying With Cancer in 7 Developed Countries.

IMPORTANCE: Differences in utilization and costs of end-of-life care among developed countries are of considerable policy interest. OBJECTIVE: To compare site of death, health care utilization, and hospital expenditures in 7 countries: Belgium, Canada, England, Germany, the Netherlands, Norway, and the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using administrative and registry data from 2010. Participants were decedents older than 65 years who died with cancer. Secondary analyses included decedents of any age, decedents older than 65 years with lung cancer, and decedents older than 65 years in the United States and Germany from 2012. MAIN OUTCOMES AND MEASURES: Deaths in acute care hospitals, 3 inpatient measures (hospitalizations in acute care hospitals, admissions to intensive care units, and emergency department visits), 1 outpatient measure (chemotherapy episodes), and hospital expenditures paid by insurers (commercial or governmental) during the 180-day and 30-day periods before death. Expenditures were derived from country-specific methods for costing inpatient services. RESULTS: The United States (cohort of decedents aged >65 years, N = 211,816) and the Netherlands (N = 7216) had the lowest proportion of decedents die in acute care hospitals (22.2.% and 29.4%, respectively). A higher proportion of decedents died in acute care hospitals in Belgium (N = 21,054; 51.2%), Canada (N = 20,818; 52.1%), England (N = 97,099; 41.7%), Germany (N = 24,434; 38.3%), and Norway (N = 6636; 44.7%). In the last 180 days of life, 40.3% of US decedents had an intensive care unit admission compared with less than 18% in other reporting nations. In the last 180 days of life, mean per capita hospital expenditures were higher in Canada (US $21,840), Norway (US $19,783), and the United States (US $18,500), intermediate in Germany (US $16,221) and Belgium (US $15,699), and lower in the Netherlands (US $10,936) and England (US $9342). Secondary analyses showed similar results. CONCLUSIONS AND RELEVANCE: Among patients older than 65 years who died with cancer in 7 developed countries in 2010, end-of-life care was more hospital-centric in Belgium, Canada, England, Germany, and Norway than in the Netherlands or the United States. Hospital expenditures near the end of life were higher in the United States, Norway, and Canada, intermediate in Germany and Belgium, and lower in the Netherlands and England. However, intensive care unit admissions were more than twice as common in the United States as in other countries.

Health technology assessment of medical devices: a survey of non-European union agencies.

OBJECTIVES: The aim of this study was to review and compare current health technology assessment (HTA) activities for medical devices across non-European Union HTA agencies. METHODS: HTA activities for medical devices were evaluated from three perspectives: organizational structure, processes, and methods. Agencies were primarily selected upon membership of existing HTA networks. The data collection was performed in two stages: stage 1-agency Web-site assessment using a standardized questionnaire, followed by review and validation of the collected data by a representative of the agency; and stage 2-semi-structured telephone interviews with key informants of a sub-sample of agencies. RESULTS: In total, thirty-six HTA agencies across twenty non-EU countries assessing medical devices were included. Twenty-seven of thirty-six (75 percent) agencies were judged at stage 1 to have adopted HTA-specific approaches for medical devices (MD-specific agencies) that were largely organizational or procedural. There appeared to be few differences in the organization, process and methods between MD-specific and non-MD-specific agencies. Although the majority (69 percent) of both categories of agency had specific methods guidance or policy for evidence submission, only one MD-specific agency had developed methodological guidelines specific to medical devices. In stage 2, many MD-specific agencies cited insufficient resources (budget, skilled employees), lack of coordination (between regulator and reimbursement bodies), and the inability to generalize findings from evidence synthesis to be key challenges in the HTA of medical devices. CONCLUSIONS: The lack of evidence for differentiation in scientific methods for HTA of devices raises the question of whether HTA needs to develop new methods for medical devices but rather adapt existing methodological approaches. In contrast, organizational and/or procedural adaptation of existing HTA agency frameworks to accommodate medical devices appear relatively commonplace.

Health literacy, governance and systems leadership contribute to the implementation of the One Health approach: a virtuous circle.

One Health is an important approach to addressing health threats and promoting health through interdisciplinary health, policy, legislation and leadership research to achieve better human and animal health and better outcomes for the planet. The Covid-19 pandemic has triggered an urgent awareness of the need to develop innovative integrative solutions to address root causes of such threats to health, which requires collaboration across disciplines and amongst different sectors and communities. We explore how achieving the Quadripartite Organizations' One Health Joint Plan of Action can be supported by the concepts of 'One Health literacy' and 'One Health governance' and promote both academic and policy dialogue. We show how One Health literacy and One Health governance influence and reinforce each other, while an interdisciplinary systems leadership approach acts as a catalyst and mechanism for understanding and enacting change. Based on our understanding of how these elements influence the implementation of the One Health approach, we describe a model for considering how external triggering events such as the Covid-19 pandemic may prompt a virtuous circle whereby exposure to and exploration of One Health issues may lead to improved One Health literacy and to better governance. We close with recommendations to international organisations, national governments and to leaders in policy, research and practice to enhance their influence on society, the planetary environment, health and well-being.

Are the European reference networks for rare diseases ready to embrace machine learning? A mixed-methods study.

BACKGROUND: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application. METHODS: We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs. RESULTS: The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders' opinions and expectations, including the views of patient organisations. CONCLUSIONS: We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies.

An econometric approach to aggregating multiple cardiovascular outcomes in German hospitals.

OBJECTIVE: Development of an aggregate quality index to evaluate hospital performance in cardiovascular events treatment. METHODS: We applied a two-stage regression approach using an accelerated failure time model based on variance weights to estimate hospital quality over four cardiovascular interventions: elective coronary bypass graft, elective cardiac resynchronization therapy, and emergency treatment for acute myocardial infarction. Mortality and readmissions were used as outcomes. For the estimation we used data from a statutory health insurer in Germany from 2005 to 2016. RESULTS: The precision-based weights calculated in the first stage were higher for mortality than for readmissions. In general, teaching hospitals performed better in our ranking of hospital quality compared to non-teaching hospitals, as did private not-for-profit hospitals compared to hospitals with public or private for-profit ownership. DISCUSSION: The proposed approach is a new method to aggregate single hospital quality outcomes using objective, precision-based weights. Likelihood-based accelerated failure time models make use of existing data more efficiently compared to widely used models relying on dichotomized data. The main advantage of the variance-based weights approach is that the extent to which an indicator contributes to the aggregate index depends on the amount of its variance.

Why the US spends more treating high-need high-cost patients: a comparative study of pricing and utilization of care in six high-income countries.

One of the most pressing challenges facing most health care systems is rising costs. As the population ages and the demand for health care services grows, there is a growing need to understand the drivers of these costs across systems. This paper attempts to address this gap by examining utilization and spending of the course of a year for two specific high-need high-cost patient types: a frail older person with a hip fracture and an older person with congestive heart failure and diabetes. Data on utilization and expenditure is collected across five health care settings (hospital, post-acute rehabilitation, primary care, outpatient specialty and drugs), in six countries (Canada (Ontario), France, Germany, Spain (Aragon), Sweden and the United States (fee for service Medicare) and used to construct treatment episode Purchasing Power Parities (PPPs) that compare prices using baskets of goods from the different care settings. The treatment episode PPPs suggest other countries have more similar volumes of care to the US as compared to other standardization approaches, suggesting that US prices account for more of the differential in US health care expenditures. The US also differs with regards to the share of expenditures across care settings, with post-acute rehab and outpatient speciality expenditures accounting for a larger share of the total relative to comparators.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

After the four-year transition period: Is the European Union's Medical Device Regulation of 2017 likely to achieve its main goals?

Following a series of major scandals over the past two decades, the medical device industry is now undergoing a major regulatory change: the implementation of the European Union Medical Device Regulation (MDR) of 2017. After a transitional period of four years, the MDR became fully binding in May 2021. Although the medium- and long-term impacts of the MDR are still unclear, a range of scholars, health care professionals, and industry representatives have begun to publish early evidence and publicize their views on how the new regulation may impact free trade and patient safety. Even a cursory view of their output reveals hypotheses and opinions that could hardly be more divergent. The reasons for this disagreement are unclear and may extend beyond the different interests of the various stakeholder groups. To find out why this might be the case, we examine the MDR and seek to improve scholarly understanding of this most extensive regulation of medical devices since the early 1990s. We offer policymakers suggestions to help them improve future regulation. Based on theoretical considerations, we conclude that while the MDR is highly likely to strengthen the internal market of the EU, its impact on patient safety will remain unclear as long as there are no comprehensive studies on this topic that are based on empirical data.

How to pay primary care physicians for SARS-CoV-2 vaccinations: An analysis of 43 EU and OECD countries.

Vaccinations are crucial to fighting SARS-CoV-2, and high coverage rates can in most countries probably only be achieved with the involvement of primary care physicians (PCPs). We aimed to explore how SARS-CoV-2 vaccination payment schemes in 43 countries differ with regard to the (i) type of payment scheme, (ii) amount paid, (iii) degree of bundling, and (iv) use of pay-for-performance elements. We collected information on payments and health system characteristics, such as PCP income and employment status, in all EU and OECD countries over time. We regressed the payment amount on the income of PCPs for countries with activity-dependent schemes using a linear regression (OLS), and we interpreted the residuals of this regression as a vaccination payment index. The majority of countries (30/43) had chosen payment schemes that reward PCPs for the activity they perform. Seventeen countries paid less per vaccination than the income-adjusted average, whereas 13 countries paid more. Twelve countries used pay-for-performance elements.

Improving health care from the bottom up: Factors for the successful implementation of kaizen in acute care hospitals.

BACKGROUND: Kaizen-a management technique increasingly employed in health care-enables employees, regardless of their hierarchy level, to contribute to the improvement of their organization. The approach puts special emphasis on frontline employees because it represents one of their main opportunities to participate directly in decision making. In this study, we aimed to (1) understand the experiences of nurses in two hospitals that had recently implemented kaizen, and (2) identify factors affecting the implementation of the technique. METHODS: By means of purposeful sampling, we selected 30 nurses from different units in two private acute care hospitals in Switzerland in May 2018. We used the Organizational Transformation Model to conduct semi-structured interviews and perform qualitative content analysis. Lastly, originating from Herzberg's motivation theory, we suggest two types of factor influencing the implementation of kaizen-hygiene factors that may prevent nurses from getting demotivated, and motivational factors that may boost their motivation. RESULTS: Nurses generally experienced kaizen as a positive practice that enabled them to discuss work-related activities in a more comprehensive manner. In some cases, however, a lack of visible improvement in the workplace lowered nurses' motivation to make suggestions. Nurses' attitudes towards kaizen differed across both hospitals depending on the available managerial support, resources such as infrastructure and staffing levels. CONCLUSIONS: From our findings, we derived several coping strategies to help health practitioners implement kaizen for the benefit of their organization and employees: Strong managerial support, appropriate use of kaizen tools, and a greater sense of team cohesion, among other factors, can influence how effectively hospital teams implement kaizen. To reap the benefits of kaizen, hospital managers should promote the exchange of opinions across hierarchy levels, allocate the necessary resources in terms of personnel and infrastructure, and show nurses how the technique can help them improve their workplace.

Regulatory and HTA early dialogues in medical devices.

INTRODUCTION: Specific guidance and examples for health technology assessment (HTA) of medical devices are scarce in medical device development. A more intense dialogue of competent authorities, HTA agencies, and manufactures may improve evidence base on clinical and cost-effectiveness. Especially as the new Medical Device Regulation requires more clinical evidence. METHODS: We explore the perceptions of manufacturers, competent authorities, and HTA agencies towards such dialogues and investigate how they should be designed to accelerate the translational process from development to patient access using semi-structured interviews. We synthesized the evidence from manufacturers, competent authorities, and HTA agencies from 14 different jurisdictions across Europe. RESULTS: Eleven HTA agencies, four competent authorities, and eight manufacturers of high-risk devices expressed perceptions on the current situation and the expected development of three types of early dialogues. DISCUSSION: The MDR has to be taken into account when designing the early dialogue processes. Transferring insights from medicinal product regulation is limited as the regulatory pathways differ substantially. CONCLUSION: Early dialogues promise to accelerate the translational process and to provide faster access to innovative medical devices. However, health policy-makers should promote and fully establish regulatory and HTA early dialogues before introducing parallel early dialogues of regulatory, HTA agencies, and manufacturers. For initiating change, the legislator must create the legal basis and set the appropriate incentives for manufacturers.