Availability and financing of CAR-T cell therapies: A cross-country comparative analysis.

Chimeric antigen receptor T-cell therapies (CAR-T therapies) are a type of advanced therapy medicinal product (ATMP) that belong to a new generation of personalised cancer immunotherapies. This paper compares the approval, availability and financing of CAR-T cell therapies in ten countries. It also examines the implementation of this type of ATMP within the health care system, describing the organizational elements of CAR-T therapy delivery and the challenges of ensuring equitable access to all those in need, taking a more systems-oriented view. It finds that the availability of CAR-T therapies varies across countries, reflecting the heterogeneity in the organization and financing of specialised care, particularly oncology care. Countries have been cautious in designing reimbursement models for CAR-T cell therapies, establishing limited managed entry arrangements under public payers, either based on outcomes or as an evidence development scheme to allow for the study of real-world therapeutic efficacy. The delivery model of CAR-T therapies is concentrated around existing experienced cancer centres and highlights the need for high networking and referral capacity. Some countries have transparent and systematic eligibility criteria to help ensure more equitable access to therapies. Overall, as with other pharmaceuticals, there is limited transparency in pricing, eligibility criteria and budgeting decisions in this therapeutic area.

Innovations in pharmaceutical policies and learnings for sustainable access to affordable medicines.

Sustainable access to affordable medicines remains a public health issue globally, including for high-income countries. To foster the debate on avenues for the future, the fifth PPRI Conference held in Vienna on 25 and 26 April 2024 will offer a forum for the debate on innovating pharmaceutical policymaking to develop and implement futureproof policy options, which are able to address current and future challenges. The Conference invites a broad audience of stakeholders, including researchers, policymakers, payers, patients, industry and health professionals. The conference topics are organised in three strands: Strand 1 on 'Local challenges, global learnings' aims to contribute to lively discussions on the implementation of pharmaceutical policies across the globe. Best-practice examples will be presented, supplemented by case studies of less effective policies which can offer rich learnings. Strand 2 on 'Strengthening the evidence base' is the place for presentations and discussions on topics such as health technology assessments, managed entry agreements and real-world data. Strand 3 'Futureproofing pharmaceutical policies' is particularly dedicated to explore innovation in policymaking to achieve sustainable access to affordable medicines.

Utilization of innovative medical technologies in German inpatient care: does evidence matter?

BACKGROUND: The reimbursement of new technologies in inpatient care is not always linked to a requirement for evidence-based evaluation of patient benefit. In Germany, every new technology approved for market was until recently eligible for reimbursement in inpatient care unless explicitly excluded. The aim of this work was (1) to investigate the type of evidence that was available at the time of introduction of 25 innovative technologies and how this evidence evolved over time, and (2) to explore the relationship between clinical evidence and utilization for these technologies in German inpatient care. METHODS: This study combined different methods. A systematic search for evidence published between 2003 and 2017 was conducted in four bibliographic databases, clinical trial registries, resources for clinical guidelines, and health technology assessment-databases. Information was also collected on funding mechanisms and safety notices. Utilization was measured by hospital procedures captured in claims data. The body of evidence, funding and safety notices per technology were analyzed descriptively. The relationship between utilization and evidence was explored empirically using a multilevel regression analysis. RESULTS: The number of included publications per technology ranges from two to 498. For all technologies, non-comparative studies form the bulk of the evidence. The number of randomized controlled clinical trials per technology ranges from zero to 19. Some technologies were utilized for several years without an adequate evidence base. A relationship between evidence and utilization could be shown for several but not all technologies. CONCLUSIONS: This study reveals a mixed picture regarding the evidence available for new technologies, and the relationship between the development of evidence and the use of technologies over time. Although the influence of funding and safety notices requires further investigation, these results re-emphasize the need for strengthening market approval standards and HTA pathways as well as approaches such as coverage with evidence development.

Digital Health Applications (DiHA): Approaches to develop a reimbursement process for the statutory health insurance in Austria.

Purpose: To elaborate a concept for implementing digital health applications (DiHA), including prioritisation criteria (PC) for the Austrian context and an overview of available prioritised DiHAs. Methods: Based on European DiHA-listings and input by Austrian experts, a categorised meta-directory of DiHAs was created. PC were developed to reflect, inter alia, the provisions of the Austrian General Insurance Act, and were applied to the meta-directory to identify DiHAs potentially relevant for the Austrian statutory health insurance. An iterative process with expert involvement was used to tailor an existing reimbursement framework to the Austrian setting. Results: The meta-directory comprised 132 DiHAs. Developed PC focused on plausibility (German language) and legal aspects (treatment/monitoring of chronic conditions), while other criteria (e.g. interoperability standards) were considered optional. After applying the PC, 38 DiHAs were potentially relevant in the Austrian setting. Of these, only seven supported current health record integration. Most of the prioritised DiHAs reported on CE marking (29/38) and data protection (35/38), while reporting on risk class (10/38) and technical algorithms (0/38) was sparse. For DiHA reimbursement, a four-step process is proposed: identification (ideally based on needs assessment); filtering based on PC; review of technical, regulatory and evidentiary requirements; and health technology assessment. Conclusion: The proposed concept can offer guidance for policy makers (e.g., on prioritising available DiHAs) and may further foster scientific debate with regard to DiHA implementation. Further discussion on how to fully incorporate regulatory, technical, and evidentiary criteria is needed. Attention should be given to national implementation requirements, re-assessment criteria, and appropriate remuneration schemes.

Challenges and opportunities for incentivising antibiotic research and development in Europe.

Antimicrobial, and particularly antibiotic resistance are one of the world's biggest challenges today, and urgent action is needed to reinvigorate the antibiotic development pipeline. To inform policy discussions during and after the 2023 Swedish Presidency of the Council of the European Union, we critically appraise incentive options recently proposed by the European Commission, and member states, and consider what has been achieved over the last two decades in relation to antibiotic research and development. While several new antibiotics have achieved regulatory approval in recent years, almost none have innovative characteristics such as new chemical classes or novel mechanisms of action. We consider four incentive options to incentivise research and development of new antibiotics, including subscription payments, market entry rewards, transferable exclusivity extensions, and milestone payments. While each option has advantages and drawbacks, a combination of incentives may be required and continued investment is needed by the EU in push incentives, such as direct funding and grants, to incentivise drug discovery and preclinical stages of development. The EU must also coordinate with international initiatives and support access to new and pre-existing antibiotics in LMICs through platforms such as the WHO, and G7 and G20 group of countries.

How did the COVID-19 pandemic affect inpatient care for children in Germany? An exploratory analysis based on national hospital discharge data.

BACKGROUND: The delivery of health services around the world faced considerable disruptions during the COVID-19 pandemic. While this has been discussed for a number of conditions in the adult population, related patterns have been studied less for children. In light of the detrimental effects of the pandemic, particularly for children and young people under the age of 18, it is pivotal to explore this issue further. METHODS: Based on complete national hospital discharge data available via the German National Institute for the Reimbursement of Hospitals (InEK) data browser, we compare the top 30 diagnoses for which children were hospitalised in 2019, 2020, 2021 and 2022. We analyse the development of monthly admissions between January 2019 and December 2022 for three tracers of variable time-sensitivity: acute lymphoblastic leukaemia (ALL), appendicitis/appendectomy and tonsillectomy/adenoidectomy. RESULTS: Compared to 2019, total admissions were approximately 20% lower in 2020 and 2021, and 13% lower in 2022. The composition of the most frequent principal diagnoses remained similar across years, although changes in rank were observed. Decreases were observed in 2020 for respiratory and gastrointestinal infections, with cases increasing again in 2021. The number of ALL admissions showed an upward trend and a periodicity prima vista unrelated to pandemic factors. Appendicitis admissions decreased by about 9% in 2020 and a further 8% in 2021 and 4% in 2022, while tonsillectomies/adenoidectomies decreased by more than 40% in 2020 and a further 32% in 2021 before increasing in 2022; for these tracers, monthly changes are in line with pandemic waves. CONCLUSIONS: Hospital care for critical and urgent conditions among patients under the age of 18 was largely upheld in Germany during the COVID-19 pandemic, potentially at the expense of elective treatments. There is an alignment between observed variations in hospitalisations and pandemic mitigation measures, possibly also reflecting changes in demand. This study highlights the need for comprehensive, intersectoral data that would be necessary to better understand changing demand, unmet need/foregone care and shifts from inpatient to outpatient care, as well as their link to patient outcomes and health care efficiency.

Health and Care Data: Approaches to data linkage for evidence-informed policy.

An indispensable prerequisite for answering research questions in health services research is the availability and accessibility of comprehensive, high-quality data. It can be assumed that health services research in the coming years will be increasingly based on data linkage, i.e., the linking, or connecting, of several data sources based on suitable common key variables. A range of approaches to data collection, storage, linkage and availability exists across countries, particularly for secondary research purposes (i.e., the use of data initially collected for other purposes), such as health systems research. The main goal of this review is to develop an overview of, and gain insights into, current approaches to linking data sources in the context of health services research, with the view to inform policy, based on existing practices in high-income countries in Europe and beyond. In doing so, another objective is to provide lessons for countries looking for possible or alternative approaches to data linkage. Thirteen country case studies of data linkage approaches were selected and analysed. Rather than being comprehensive, this review aimed to identify varied and potentially useful case studies to showcase different approaches to data linkage worldwide. A conceptual framework was developed to guide the selection and description of case studies. Information was first identified and collected from publicly available sources and a profile was then created for each country and each case study; these profiles were forwarded to appropriate country experts for validation and completion. The report presents an overview of the included countries and their case studies (Chapter 2), with key data per country and case study in the appendices. This is followed by a closer look at the possibilities of using routine data (Chapter 3); the different approaches to linkage (Chapter 4); the different access routes for researchers (Chapter 5); the use of data for research from electronic patient or health records (Chapter 6); foundational considerations related to data safety, privacy and governance (Chapter 7); recent developments in cross-border data sharing and the European Health Data Space (Chapter 8); and considerations of changes and responses catalysed by the COVID-19 pandemic as related to the generation and secondary use of data (Chapter 9). The review ends with overall conclusions on the necessary characteristics of data to inform research relevant for policy and highlights some insights to inspire possible future solutions - less or more disruptive - for countries looking to expand their use of data (Chapter 10). It emphasises that investing in data linkage for secondary use will not only contribute to the strengthening of national health systems, but also promote international cooperation and contribute to the international visibility of scientific excellence.

Giant cell tumor of the patellar tendon sheath in childhood: case report.

The aim of this study was to report a rare case of a giant cell tumor of the patellar tendon sheath. This indicates the diagnostic procedures and treatment options for giant cell tumors of the patellar tendon. This study reported a case of a 13-year-old male patient with a giant cell tumor of the tendon sheath. In our case, open arthrotomy was performed with complete surgical excision of the lesion. Histopathological examination revealed a giant cell tumor. At the last follow-up, 2 years after surgery, no complications were reported. The giant cell tumor of the patellar tendon sheath is an uncommon benign tumor. It mimics common knee symptoms. A differential diagnosis is definitely a challenge. Available operation approaches have demonstrated similar results, which lead to symptom relief and a low recurrence rate.

Mapping Studies to Estimate Health-State Utilities From Nonpreference-Based Outcome Measures: A Systematic Review on How Repeated Measurements are Taken Into Account.

OBJECTIVES: Mapping algorithms are developed using data sets containing patient responses to a preference-based questionnaire and another health-related quality-of-life questionnaire. When data sets include repeated measurements from the same individuals over time, the assumption of observations' independence, required by standard models, is violated, and standard errors are underestimated. This review aimed to identify how studies deal with methodological challenges of repeated measurements, provide an overview of practice to date, and potential implications for future work. METHODS: We conducted a systematic literature search of MEDLINE, Cumulative Index to Nursing and Allied Health Literature, specialized databases, and previous systematic reviews. A data template was used to extract, among others, start and target instruments if the data set(s) used for estimation and validation had repeated measurements per patient, used regression techniques, and which (if any) adjustments were made for repeated measurements. RESULTS: We identified 278 publications developing at least 1 mapping algorithm. Of the 278 publications, 121 used a data set with repeated measurements, among which 92 used multiple time points for estimation, and 39 selected specific time points to have 1 observation per participant. A total of 36 studies did not account for repeated measurements. An adjustment was conducted using cluster-robust standard errors (21), random-effects models (30), generalized estimating equations (7), and other methods (7). CONCLUSIONS: The inconsistent use of methods to account for interdependent observations in the literature indicates that mapping guidelines should include recommendations on how to deal with repeated measurements, and journals should update their guidelines accordingly.

Benefit Assessment and Reimbursement of Digital Health Applications: Concepts for Setting Up a New System for Public Coverage.

In Germany, some digital health applications (DiHA) became reimbursable through the statutory health insurance system with the adoption of the Digital Healthcare Act in 2019. Approaches and concepts for the German care context were developed in an iterative process, based on existing concepts from international experience. A DiHA categorization was developed that could be used as a basis to enable the creation of a reimbursed DiHA repository, and to derive evidence requirements for coverage and reimbursement for each DiHA. The results provide an overview of a possible classification of DiHA as well as approaches to assessment and evaluation. The structure of remuneration and pricing in connection with the formation of groups is demonstrated.

Health care patterns and policies in 18 European countries during the first wave of the COVID-19 pandemic: an observational study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has developed into an unprecedented global challenge. Differences between countries in testing strategies, hospitalization protocols as well as ensuring and managing ICU capacities can illustrate initial responses to a major health system shock, and steer future preparedness activities. METHODS: Publicly available daily data for 18 European countries were retrieved manually from official sources and documented in an Excel table (March-July 2020). The ratio of tests to cases, the share of hospitalizations out of all cases and the share of ICU admissions out of all hospitalizations were computed using 7-day rolling averages per 100 000 population. Information on country policies was collected from the COVID-19 Health System Response Monitor of the European Observatory on Health Systems and Policies. Information on health care capacities, expenditure and utilization was extracted from the Eurostat health database. RESULTS: There was substantial variation across countries for all studied variables. In all countries, the ratio of tests to cases increased over time, albeit to varying degrees, while the shares of hospitalizations and ICU admissions stabilized, reflecting the evolution of testing strategies and the adaptation of COVID-19 health care delivery pathways, respectively. Health care patterns for COVID-19 at the outset of the pandemic did not necessarily follow the usual health service delivery pattern of each health system. CONCLUSIONS: This study enables a general understanding of how the early evolution of the pandemic influenced and was influenced by country responses and clearly demonstrates the immense potential for cross-country learning.

Exploring variation of coverage and access to dental care for adults in 11 European countries: a vignette approach.

BACKGROUND: Oral health, coupled with rising awareness on the impact that limited dental care coverage has on oral health and general health and well-being, has received increased attention over the past few years. The purpose of the study was to compare the statutory coverage and access to dental care for adult services in 11 European countries using a vignette approach. METHODS: We used three patient vignettes to highlight the differences of the dimensions of coverage and access to dental care (coverage, cost-sharing and accessibility). The three vignettes describe typical care pathways for patients with the most common oral health conditions (caries, periodontal disease, edentulism). The vignettes were completed by health services researchers knowledgeable on dental care, dentists, or teams consisting of a health systems expert working together with dental specialists. RESULTS: Completed vignettes were received from 11 countries: Bulgaria, Estonia, France, Germany, Republic of Ireland (Ireland), Lithuania, the Netherlands, Poland, Portugal, Slovakia and Sweden. While emergency dental care, tooth extraction and restorative care for acute pain due to carious lesions are covered in most responding countries, root canal treatment, periodontal care and prosthetic restoration often require cost-sharing or are entirely excluded from the benefit basket. Regular dental visits are also limited to one visit per year in many countries. Beyond financial barriers due to out-of-pocket payments, patients may experience very different physical barriers to accessing dental care. The limited availability of contracted dentists (especially in rural areas) and the unequal distribution and lack of specialised dentists are major access barriers to public dental care. CONCLUSIONS: According to the results, statutory coverage of dental care varies across European countries, while access barriers are largely similar. Many dental services require substantial cost-sharing in most countries, leading to high out-of-pocket spending. Socioeconomic status is thus a main determinant for access to dental care, but other factors such as geography, age and comorbidities can also inhibit access and affect outcomes. Moreover, coverage in most oral health systems is targeted at treatment and less at preventative oral health care.

Reimbursement decisions for medical services in Austria: an analysis of influencing factors for the hospital individual services catalogue between 2008 and 2020.

OBJECTIVES: To (1) describe the (evidence-based) reimbursement process of hospital individual services, (2) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (3) elaborate potential aspects that play a role in the decision-making process in Austria. METHOD: The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analysed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decision makers. RESULTS: 118 evidence-based recommendations were analysed. There were 93 (78.8%) negative and 25 (21.2%) positive evidence-based recommendations. In total, 107 out of 118 evidence-based recommendations (90.1%) did not lead to a deviating reimbursement decision. We identified six aspects that may have played a role in the decision-making process for the annual maintenance of the hospital individual service catalogue, with clinical evidence being the most notable. Further aspects included quality assurance/organisational aspects (i.e., structural quality assurance), costs (if comparable to already existing medical services, not: cost-effectiveness), procedural aspects (e.g., if certain criteria for adoption have not been met formally through the proposals), "other countries" (i.e., taking into account how other countries decided) and situational aspects (such as the COVID-19 pandemic). CONCLUSIONS: There is good accordance between evidence-based recommendations and reimbursement decisions regarding hospital individual services in Austria. Beyond clinical evidence, organisational aspects seem to be considered often with regard to quality assurance but costs do not appear to play a major role. The Austrian system has mechanisms in place that can restrict widespread adoption of novel hospital individual services with uncertain clinical benefits. Future studies could investigate how well these mechanisms work and how they compare to other health systems in Europe.

A country-level analysis comparing hospital capacity and utilisation during the first COVID-19 wave across Europe.

BACKGROUND: The exponential increase in SARS-CoV-2 infections during the first wave of the pandemic created an extraordinary overload and demand on hospitals, especially intensive care units (ICUs), across Europe. European countries have implemented different measures to address the surge ICU capacity, but little is known about the extent. The aim of this paper is to compare the rates of hospitalised COVID-19 patients in acute and ICU care and the levels of national surge capacity for intensive care beds across 16 European countries and Lombardy region during the first wave of the pandemic (28 February to 31 July). METHODS: For this country level analysis, we used data on SARS-CoV-2 cases, current and/or cumulative hospitalised COVID-19 patients and current and/or cumulative COVID-19 patients in ICU care. To analyse whether capacities were exceeded, we also retrieved information on the numbers of hospital beds, and on (surge) capacity of ICU beds during the first wave of the COVID-19 pandemic from the COVID-19 Health System Response Monitor (HSRM). Treatment days and mean length of hospital stay were calculated to assess hospital utilisation. RESULTS: Hospital and ICU capacity varied widely across countries. Our results show that utilisation of acute care bed capacity by patients with COVID-19 did not exceed 38.3% in any studied country. However, the Netherlands, Sweden, and Lombardy would not have been able to treat all patients with COVID-19 requiring intensive care during the first wave without an ICU surge capacity. Indicators of hospital utilisation were not consistently related to the number of SARS-CoV-2 infections. The mean number of hospital days associated with one SARS-CoV-2 case ranged from 1.3 (Norway) to 11.8 (France). CONCLUSION: In many countries, the increase in ICU capacity was important to accommodate the high demand for intensive care during the first COVID-19 wave.

Innovation, value and reimbursement in radiation and complex surgical oncology: Time to rethink.

BACKGROUND AND PURPOSE: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews. MATERIAL AND METHODS: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models. RESULTS: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy. CONCLUSION: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice.

Innovation, value and reimbursement in radiation and complex surgical oncology: Time to rethink.

BACKGROUND AND PURPOSE: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews. MATERIAL AND METHODS: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models. RESULTS: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy. CONCLUSION: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice.

HIT-6 and EQ-5D-5L in patients with migraine: assessment of common latent constructs and development of a mapping algorithm.

OBJECTIVE: The aims of this study were to assess whether there is a conceptual overlap between the questionnaires HIT-6 and EQ-5D and to develop a mapping algorithm allowing the conversion of HIT-6 to EQ-5D utility scores for Germany. METHODS: This study used data from an ongoing randomised controlled trial for patients suffering from migraine. We assessed the conceptual overlap between the two instruments with correlation matrices and exploratory factor analysis. Linear regression, tobit, mixture, and two-part models were used for mapping, accounting for repeated measurements, tenfold cross-validation was conducted to validate the models. RESULTS: We included 1010 observations from 410 patients. The EQ-5D showed a substantial ceiling effect (47.3% had the highest score) but no floor effect, while the HIT-6 showed a very small ceiling effect (0.5%). The correlation between the instruments' total scores was moderate (- 0.30), and low to moderate among each domain (0.021-0.227). The exploratory factor analysis showed insufficient conceptual overlap between the instruments, as they load on different factors. Thus, there is reason to believe that the instruments' domains do not capture the same latent constructs. To facilitate future mapping, we provide coefficients and a variance-covariance matrix for the preferred model, a two-part model with the total HIT-6 score as the explanatory variable. CONCLUSION: This study showed that the German EQ-5D and the HIT-6 lack the conceptual overlap needed for appropriate mapping. Thus, the estimated mapping algorithms should only be used as a last resort for estimating utilities to be employed in economic evaluations.