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.

An EQ-5D-5L Value Set for Belgium.

OBJECTIVE: This study aimed to establish a Belgian EQ-5D-5L value set based on the preferences of the adult Belgian general population. METHODS: The most recent EuroQol Valuation Technology (EQ-VT 2.1) protocol for EQ-5D-5L valuation studies was followed. Computer-assisted personal interviews were carried out in a representative sample of the adult Belgian population. Potential respondents were randomly selected from the National Register using a multistage, stratified, cluster sampling with unequal probability design. Each respondent valued 10 or 11 health states using composite time trade-off (cTTO) and 14 health states in seven paired choice tasks using a discrete choice experiment (DCE). Different model specifications were explored and assessed based on logical consistency, goodness of fit, predictive accuracy and theoretical considerations. RESULTS: A total of 892 respondents were included in the analyses. The sample was representative of the Belgian adult population in terms of age, sex, region of residence, educational attainment, labour market status, self-assessed health status and health-related quality of life (HRQoL). The preferred model specification was a hybrid (DCE and cTTO data combined) multiplicative eight-coefficient model with intercept random effects and correction for heteroskedasticity. Values range from - 0.532 to 1. Loss of HRQoL is highest in the dimension pain/discomfort, closely followed by anxiety/depression. CONCLUSIONS: This study developed a Belgian EQ-5D-5L value set, based on the preferences of the Belgian adult general population. It provides opportunities for future clinical and economic evaluations in healthcare, for the measurement of patient-reported outcomes and for population health assessments.

Tackling the COVID-19 pandemic: Initial responses in 2020 in selected social health insurance countries in Europe☆.

Countries with social health insurance (SHI) systems display some common defining characteristics - pluralism of actors and strong medical associations - that, in dealing with crisis times, may allow for common learnings. This paper analyses health system responses during the COVID-19 pandemic in eight countries representative of SHI systems in Europe (Austria, Belgium, France, Germany, Luxembourg, the Netherlands, Slovenia and Switzerland). Data collection and analysis builds on the methodology and content in the COVID-19 Health System Response Monitor (HSRM) up to November 2020. We find that SHI funds were, in general, neither foreseen as major stakeholders in crisis management, nor were they represented in crisis management teams. Further, responsibilities in some countries shifted from SHI funds to federal governments. The overall organisation and governance of SHI systems shaped how countries responded to the challenges of the pandemic. For instance, coordinated ambulatory care often helped avoid overburdening hospitals. Decentralisation among local authorities may however represent challenges with the coordination of policies, i.e. coordination costs. At the same time, bottom-up self-organisation of ambulatory care providers is supported by decentralised structures. Providers also increasingly used teleconsultations, which may remain part of standard practice. It is recommended to involve SHI funds actively in crisis management and in preparing for future crisis to increase health system resilience.

Balancing financial incentives during COVID-19: A comparison of provider payment adjustments across 20 countries.

Provider payment mechanisms were adjusted in many countries in response to the COVID-19 pandemic in 2020. Our objective was to review adjustments for hospitals and healthcare professionals across 20 countries. We developed an analytical framework distinguishing between payment adjustments compensating income loss and those covering extra costs related to COVID-19. Information was extracted from the Covid-19 Health System Response Monitor (HSRM) and classified according to the framework. We found that income loss was not a problem in countries where professionals were paid by salary or capitation and hospitals received global budgets. In countries where payment was based on activity, income loss was compensated through budgets and higher fees. New FFS payments were introduced to incentivize remote services. Payments for COVID-19 related costs included new fees for out- and inpatient services but also new PD and DRG tariffs for hospitals. Budgets covered the costs of adjusting wards, creating new (ICU) beds, and hiring staff. We conclude that public payers assumed most of the COVID-19-related financial risk. In view of future pandemics policymakers should work to increase resilience of payment systems by: (1) having systems in place to rapidly adjust payment systems; (2) being aware of the economic incentives created by these adjustments such as cost-containment or increasing the number of patients or services, that can result in unintended consequences such as risk selection or overprovision of care; and (3) periodically evaluating the effects of payment adjustments on access and quality of care.

An evaluation of managed entry agreements in Belgium: A system with threats and (high) potential if properly applied.

OBJECTIVE: To evaluate the strengths and weaknesses of managed entry agreements (MEAs) in Belgium. METHODS: All Belgian MEAs signed between 2010 and 2015 (n = 71) were studied, including the re-evaluations of 16 reimbursement requests for which the initial MEA had ended. The analysis was supported by the findings from a systematic literature review and structured interviews with Belgian stakeholders. RESULTS: The current application of MEAs provides the short-term advantage of getting a positive reimbursement decision with lower confidential prices. However, it is not clear whether the negotiated prices are in line with the added value of the interventions. Furthermore, the contracts do not provide incentives for manufacturers to gather evidence or to set public prices at an acceptable level. CONCLUSIONS: Based on our analysis of the Belgian MEAs and discussions with Belgian stakeholders, an overview of various issues and pitfalls related to the current application of the system is given. Recommendations are made related to providing correct incentives to deliver good evidence, establishing a correct link between identified uncertainties/problems and the type and content of the MEA, reducing the risk of making the system non-transparent, the importance of international collaboration, etc. in order to optimize the potential of this system. These recommendations are addressed to both the Belgian policymakers and stakeholders in other countries making use of MEAs.

Belgium: Health System Review.

The Belgian health system covers almost the entire population for a large range of services. The main source of financing is social contributions, proportional to income. The provision of care is based on the principles of independent medical practice, free choice of physician and care facility, and predominantly fee-for-service payment. The Belgian population enjoys good health and long life expectancy. This is partly due to the population's good access to many high-quality health services. However, some challenges remain in terms of appropriateness of pharmaceutical care (overuse of antibiotics and psychotropic drugs), reduced accessibility for mental health and dental care due to higher user charges, socioeconomic inequalities in health status and the need for further strengthening of prevention policies. The system must also continue to evolve to cope with an ageing population, an increase of chronic diseases and the development of new technologies. This Belgian HiT profile (2020) presents the evolution of the health system since 2014, including detailed information on new policies. The most important reforms concern the transfer of additional health competences from the Federal State to the Federated entities and the plan to redesign the landscape of hospital care. Policy-makers have also pursued the goals of further improving access to high-quality services, while maintaining the financial sustainability and efficiency of the system, resulting in the implementation of several measures promoting multidisciplinary and integrated care, the concentration of medical expertise, patient care trajectories, patient empowerment, evidence-based medicine, outcome-based care and the so-called one health approach. Cooperation with neighbouring countries on pricing and reimbursement policies to improve access to (very high price) innovative medicines are also underway. Looking ahead, because additional challenges will be highlighted by the COVID-19 crisis, a focus on the resilience of the system is expected.

CARDIOVASCULAR SCREENING OF YOUNG ATHLETES: A REVIEW OF ECONOMIC EVALUATIONS.

OBJECTIVES: Some experts have promoted preparticipative cardiovascular screening programs for young athletes and have claimed that such programs were cost-effective without performing a critical analysis of studies supporting this statement. In this systematic review, a critical assessment of economic evaluations on these programs is performed to determine if they really provide value for money. METHODS: A systematic review of economic evaluations was performed on December 24, 2014. Web sites of health technology assessment agencies, the Cochrane database of systematic review, the National Health Service Economic Evaluation Database of the Cochrane Library, EMBASE, Medline, Psychinfo, and EconLit were searched to retrieve (reviews of) economic evaluations. No language or time restrictions were imposed and predefined selection criteria were used. Selected studies were critically assessed applying a structured data extraction sheet. RESULTS: Five relevant economic evaluations were critically assessed. Results of these studies were mixed. However, those in favor of screening made (methodological) incorrect choices, of which the most important one was not taking into account a no-screening alternative as comparator. Compared with no screening, other strategies (history and physical examination or history and physical examination plus electrocardiogram) were not considered cost-effective. CONCLUSIONS: Results of primary economic evaluations should not be blindly copied without critical assessment. Economic evaluations in this field lack the support of robust evidence. Negative consequences of screening (false positive findings, overtreatment) should also be taken into account and may cause more harm than good. A mass screening of young athletes for cardiovascular diseases does not provide value for money and should be discouraged.

Pharmaceutical regulation in 15 European countries review.

In the context of pharmaceutical care, policy-makers repeatedly face the challenge of balancing patient access to effective medicines with affordability and rising costs. With the aim of guiding the health policy discourse towards questions that are important to actual and potential patients, this study investigates a broad range of regulatory measures, spanning marketing authorization to generic substitution and resulting price levels in a sample of 16 European health systems (Austria, Belgium, Denmark, England, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Portugal, Scotland, Spain and Sweden). All countries employ a mix of regulatory mechanisms to contain pharmaceutical expenditure and ensure quality and efficiency in pharmaceutical care, albeit with varying configurations and rigour. This variation also influences the extent of publicly financed pharmaceutical costs. Overall, observed differences in pharmaceutical expenditure should be interpreted in conjunction with the differing volume and composition of consumption and price levels, as well as dispensation practices and their impact on measurement of pharmaceutical costs. No definitive evidence has yet been produced on the effects of different cost-containment measures on patient outcomes. Depending on the foremost policy concerns in each country, different levers will have to be used to enable the delivery of appropriate care at affordable prices.

Development of a national position paper for chronic care: example of Belgium.

The management of chronic diseases is a prime challenge of most 21st century health care systems. Many Western countries have invested heavily in care plans oriented towards specific conditions and diseases, such as dementia and cancer. The major downside of this narrowly focused approach is that treatment of multimorbidity is ignored. This paper describes the development and main stance of a national position that proposes streamlined reforms of the Belgian health care system to improve care for patients with multiple chronic diseases. We used a combination of methods to develop this stance: literature review and stakeholders' consultation. The latter identified areas for improvement: efficiency of the health care system, coordination of care, investments in human care resources, informal caregivers' support, better accessibility, and changes in the financial payment system. The position paper list 20 recommendations that are translated into about 50 action points to reform the health care system. Chronic care tailored to the patient's needs, including implementation of multidisciplinary teamwork, new functions, task delegation in primary care, and empowerment of the patient and informal caregivers are some major areas discussed. In addition, improved support, revised payment mechanisms, and setting up a quality system, along with the tailoring of patient care, can all facilitate delivery of high quality care in patients with chronic comorbidities.

Economic evaluation of the use of point-of-care devices in patients with long term oral anticoagulation.

To examine the cost and cost-effectiveness of the use of point-of-care (POC) devices by the general practitioner (GP), in anticoagulation clinic or by the patient in self-testing (PST) and self-management (PSM), compared with standard laboratory testing to realize international normalized ratio tests for patients on long term anticoagulation therapy. An economic evaluation was performed from the Belgian health care payer's perspective using a Markov model. Outcomes data were derived from a meta-analysis and cost data were derived from claims databases. Several scenarios were tested based on number of tests and GP's contacts and probabilistic sensitivity analysis was used to handle uncertainty. Evidence on the impact of POC on mortality was only found for PSM. Therefore, a cost-effectiveness analysis was performed for PSM and for other strategies, only a cost comparison was done. With an unchanged number of tests, POC is cost-saving compared to laboratory testing (probability > 70%). In scenarios where POC induces more tests, results were different: with 52 tests/year, only PSM kept a probability of remaining cost-saving superior to 50%. Except in the case of 100% of GP consultations maintained and 52 tests/year performed, PSM resulted in significantly more "life years gained" (LYG) than usual care and was on average cost-saving. The organisation of long term oral anticoagulation monitoring should be directed towards PSM and, to a lesser extent, PST for selected and trained patients.

Comparing the quality of care across Belgian hospitals from medical basic datasets: the case of thromboembolism prophylaxis after major orthopaedic surgery.

RATIONALE, AIMS AND OBJECTIVES: In the current context, the assessment of the quality of care in daily clinical practice becomes essential. The aim of this study was to use medical basic datasets associated with information on pharmacological treatments to assess the quality of care of a prophylaxis treatment after major orthopaedic surgery and to compare hospitals' clinical practices. METHODS: The study was performed in 20 Belgian hospitals. Patients who underwent total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS) were selected retrospectively from the hospitals' 2002 and 2003 administrative databases (n = 14,991). Quality indicators assessed were incidence of venous thromboembolism, major bleeding and death. Prophylaxis analysed were enoxaparin, nadroparin and fondaparinux. RESULTS: Venous thromboembolism and major bleeding events were rare (1.9% and 1.1% respectively). Patients who underwent HFS were at greater risk of having pulmonary embolism [OR = 2.01; confidence interval (CI) = 1.38-2.92; P = 0.0002], major bleeding (OR = 4.00; CI = 2.93-5.46; P < 0.0001) or death from any cause (OR = 8.86; CI = 6.85-11.45; P < 0.0001) than patients who underwent THR or TKR. Multivariate analyses showed that the hospital variable had a significant impact on the probability to have adverse events and that patients who received enoxaparin were at greater risk of death than patients who received nadroparin (OR(enoxaparin vs fraxiparin) = 1.59; 95% CI = 1.04-2.44; P = 0.033). CONCLUSION: Results indicate that differences in thromboembolism prophylaxis practices among hospitals have a significant impact on adverse events. This reinforces the need to develop data-processing tools that enable better monitoring of quality of care.

Belgium: Health system review.

The Health Systems in Transition (HiT) profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. HiTs examine different approaches to the organization, financing and delivery of health services and the role of the main actors in health systems; describe the institutional framework, process, content and implementation of health and health care policies; and highlight challenges and areas that require more in-depth analysis. The Belgian population continues to enjoy good health and long life expectancy. This is partly due to good access to health services of high quality. Financing is based mostly on proportional social security contributions and progressive direct taxation. The compulsory health insurance is combined with a mostly private system of health care delivery, based on independent medical practice, free choice of physician and predominantly fee-for-service payment. This Belgian HiT profile (2010) presents the evolution of the health system since 2007, including detailed information on new policies. While no drastic reforms were undertaken during this period, policy-makers have pursued the goals of improving access to good quality of care while making the system sustainable. Reforms to increase the accessibility of the health system include measures to reduce the out-of-pocket payments of more vulnerable populations (low-income families and individuals as well as the chronically ill). Quality of care related reforms have included incentives to better integrate different levels of care and the establishment of information systems, among others. Additionally, several measures on pharmaceutical products have aimed to reduce costs for both the National Institute for Health and Disability Insurance (NIHDI) and patients, while maintaining the quality of care.

Comparison of three instruments assessing the quality of economic evaluations: a practical exercise on economic evaluations of the surgical treatment of obesity.

OBJECTIVES: The increasing use of full economic evaluations has led to the development of various instruments to assess their quality. The purpose of this study was to compare the frequently used British Medical Journal (BMJ) check-list and two new instruments: the Consensus Health Economic Criteria (CHEC) list and the Quality of Health Economic Studies (QHES) instrument. The analysis was based on a practical exercise on economic evaluations of the surgical treatment of obesity. METHODS: The quality of nine selected studies was assessed independently by two health economists. To compare instruments, the Spearman rank correlation coefficient was calculated for each assessor. Moreover, the test-retest reliability for each instrument was assessed with the intraclass correlation coefficient (ICC) (3,1). Finally, the inter-rater agreement for each instrument was estimated at two levels: comparison of the total score of each article by the ICC(2,1) and comparison of results per item by kappa values. RESULTS: The Spearman's rank correlation coefficient between instruments was usually high (rho > 0.70). Furthermore, test-retest reliability was good for every instruments, that is, 0.98 (95 percent CI, 0.86-0.99) for the BMJ check-list, 0.97 (95 percent CI, 0.73-0.98) for the CHEC list, and 0.95 (95 percent CI, 0.75-0.99) for the QHES instrument. However, inter-rater agreement was poor (kappa < 0.40 for most items and ICC(2,1) < or = 0.5). CONCLUSIONS: The study shows that the results of the quality assessment of economic evaluations are not so much influenced by the instrument used but more by the assessor. Therefore, quality assessments should be performed by at least two independent experts and final scoring based on consensus.

Assessing the quality of pharmacological treatments from administrative databases: the case of low-molecular-weight heparin after major orthopaedic surgery.

RATIONALE, AIMS AND OBJECTIVES: 'Real world data' are needed to assess the quality of pharmacological treatments in clinical practice. The aim of this study was to determine whether administrative databases can be used to assess the quality of prophylaxis with low-molecular-weight heparin after major orthopaedic surgery. METHODS: The study was performed in a Belgian university hospital. Patients undergoing total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) were selected retrospectively from the hospital's 2002 and 2003 administrative databases. Readmissions during the same year as the procedure were also analysed. Three quality indicators were assessed: incidence of venous thromboembolism (VTE), major bleeding and death; adherence to guidelines; and the costs of care. RESULTS: Although 70% of data were collected from administrative databases, patients' records also had to be examined. During the period studied, VTE and major bleeding events were rare. Patients undergoing HFS were at greater risk of having a pulmonary embolism [Exact odds ratio (OR)=3.78; 95% confidence interval (CI)=1.13-16.22; P=0.03] or of death from any cause (Exact OR=2.15; 95% CI=1.52-infinity; P<0.01) than patients undergoing THR or TKR. The hospital's prophylaxis protocol was not always followed. Half the patients received higher prophylaxis doses than recommended and 11% received lower doses but no impact on adverse events was demonstrated. CONCLUSION: Results show that administrative databases contain enough information to measure the frequency of adverse events but complementary data on patient weight and on non-reimbursed drugs must be extracted from the patients' records to evaluate adherence to guidelines. Our findings stress the need for better integration of information systems.

Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: clinical and pharmacoeconomic study in 50 children.

Corticosteroid-free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid-free, tacrolimus-basiliximab-based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus-steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection-free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term.

A health economic model to assess the cost-effectiveness of pegylated interferon alpha-2a and ribavirin in patients with moderate chronic hepatitis C and persistently normal alanine aminotransferase levels.

BACKGROUND AND STUDY AIMS: The treatment of patients with moderate chronic hepatitis C and persistently normal alanine aminotransferase levels is still under discussion and the cost-effectiveness of such strategy is unknown. The objective of this study was to estimate the cost-effectiveness of their treatment in comparison with no treatment. PATIENTS AND METHODS: The assessed treatment is composed of pegylated interferon alpha-2a and ribavirin, which is the current standard treatment. Two groups were studied: patients with genotype 1 and patients with genotypes 2-3. At the beginning of the study, patients were aged of 45. Long-term economic and clinical outcomes over a 30 year period were predicted using a Markov simulation model. A health care payer perspective was chosen. Data were obtained from published literature. Variations of uncertainty parameters were assessed through a sensitivity analysis. RESULTS: The incremental cost-effectiveness ratios (ICERs) were Euro 5,338/QALY for genotype 1 and Euro 1,080/QALY for genotypes 2-3. In the sensitivity analysis, ratios remained lower than Euro 20,000. A Monte Carlo simulation with 1,000 iterations gives a 95% confidence interval for the ICER of Euro 3,199 to Euro 8,972 for genotype 1 and Euro 56 to Euro 1,981 for genotypes 2-3. CONCLUSION: Even though the treatment of these patients generates a cost, it has the advantage that in comparison with no treatment, a great number of people are cured, complications are less frequent and patients gain more quality-adjusted life-year (QALY), which involves an ICER considered as acceptable for the European society (< Euro 20,000).