Determining the societal value of a prospective drug for ME/CFS in Germany.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) imposes a substantial societal and economic burden. The aim of this study is to ascertain the optimal level of public research and development (R&D) investment in Germany for a prospective drug, given the pressing need for effective treatments. METHODS: This study calculates the societal value from a German perspective by integrating health and economic outcomes in the context of public R&D investment for ME/CFS. It considers factors such as direct medical costs, productivity loss, and the effectiveness of a prospective drug. RESULTS: The anticipated introduction of a prospective drug is estimated to yield a quality-adjusted life year (QALY) gain of approximately 29,000 and a societal value of about €2.6 billion. The optimal R&D investment in Germany is estimated at €676 million, which represents about a quarter of the total investment required to bring a significant drug to market, considering diminishing returns and market constraints. Results were confirmed in the sensitivity analysis. CONCLUSIONS: The study concludes that a coordinated international approach is imperative to address the funding and market size limitations effectively in developing treatments for ME/CFS and to realize the substantial societal and economic benefits.

Was EU's COVID-19 vaccine procurement strategy irrational? A re-analysis based on cost-effectiveness considerations.

AIM: The European Union (EU) has received criticism for being slow to secure coronavirus disease (COVID-19) vaccine contracts in 2020 before the approval of the first COVID-19 vaccine. This study aimed to retrospectively analyze the EU's COVID-19 vaccine procurement strategy. To this end, the study retrospectively determined the minimum vaccine efficacy that made vaccination cost-effective from a societal perspective in Germany before clinical trial announcements in late 2020. The results were compared with the expected vaccine efficacy before the announcements. METHODS: Two strategies were analyzed: vaccination followed by the complete lifting of mitigation measures and a long-term mitigation strategy. A decision model was constructed using, for example, information on age-specific fatality rates, intensive care unit costs and outcomes, and herd protection thresholds. The base-case time horizon was 5 years. Cost-effectiveness of vaccination was determined in terms of the costs per life-year gained. The value of an additional life-year was borrowed from new, innovative oncological drugs, as cancer is a condition with a perceived threat similar to that of COVID-19. RESULTS: A vaccine with 50% efficacy against death due to COVID-19 was not clearly cost-effective compared with a long-term mitigation strategy if mitigation measures were planned to be lifted after vaccine rollout. The minimum vaccine efficacy required to achieve cost-effectiveness was 40% in the base case. The sensitivity analysis showed considerable variation around the minimum vaccine efficacy, extending above 50% for some of the input variables. CONCLUSIONS: This study showed that vaccine efficacy levels expected before clinical trial announcements did not clearly justify lifting mitigation measures from a cost-effectiveness standpoint. Hence, the EU's sluggish procurement strategy still appeared to be rational at the time of decision making.

Value-based pricing of a COVID-19 vaccine.

AIM: The purpose of this study is to determine the value-based price of a COVID-19 vaccine from a societal perspective in Germany. METHODS: A decision model was constructed using, e.g., information on age-specific fatality rates, intensive care unit (ICU) costs and outcomes, and the full vaccination rate. Three strategies were analysed: vaccination (with 95 % and 50 % efficacy against death), a mitigation strategy, and no intervention. The base-case time horizon was 5 years. The value of a vaccine includes savings from avoiding COVID-19 mitigation measures and productivity loss, as well as health benefits from preventing COVID-19 related mortality. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short term as COVID-19. RESULTS: A vaccine with a 95 % efficacy dominates the mitigation strategy strictly. The value-based price (€6,431) is thus determined by the comparison between vaccination and no intervention. The price is particularly sensitive to the full vaccination rate and the duration of vaccine protection. In contrast, the value of a vaccine with 50 % efficacy is more ambiguous. CONCLUSION: This study yields a value-based price for a COVID-19 vaccine with 95 % efficacy, which is considerably greater than the purchasing price.

The clinical and economic value of a successful shutdown during the SARS-CoV-2 pandemic in Germany.

Background and aim: A shutdown of businesses enacted during the SARS-CoV-2 pandemic can serve different goals, e.g., preventing the intensive care unit (ICU) capacity from being overwhelmed ('flattening the curve') or keeping the reproduction number substantially below one ('squashing the curve'). The aim of this study was to determine the clinical and economic value of a shutdown that is successful in 'flattening' or 'squashing the curve' in Germany. Methods: In the base case, the study compared a successful shutdown to a worst-case scenario with no ICU capacity left to treat COVID-19 patients. To this end, a decision model was developed using, e.g., information on age-specific fatality rates, ICU outcomes, and the herd protection threshold. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short term as COVID-19. Results: A shutdown that is successful in 'flattening the curve' is projected to yield an average health gain between 0.01 and 0.05 life years (0.1 to 0.6 months) per capita in the German population. The corresponding economic value ranges between €616 and €4797 per capita or, extrapolated to the total population, 1%-12% of the gross domestic product (GDP) in 2019. A shutdown that is successful in 'squashing the curve' is expected to yield a minimum health gain of 0.08 life years (1 month) per capita, corresponding to 19 % of the GDP in 2019. Results are particularly sensitive to mortality data and the prevalence of undetected cases. Conclusion: A successful shutdown is forecasted to yield a considerable gain in life years in the German population. Nevertheless, questions around the affordability and underfunding of other parts of the healthcare system emerge.

The price of curing cancer.

BACKGROUND: Health care systems around the world struggle with high prices for new cancer drugs. The purpose of this study was to conduct a gedankenexperiment and calculate how much health expenditures would change if a cure for cancer through pharmaceutical treatment were made available. The cancer cure was conceived to eliminate both cancer deaths and the underlying morbidity burden of cancer. Furthermore, the cure was hypothesized to arrive in incremental steps but at infinitesimally small time intervals (resulting, effectively, in an immediate cure). METHODS: The analysis used secondary data and was conducted from the viewpoint of the German social health insurance. As its underlying method, it used a cause-elimination life-table approach. To account for the age distribution of the population, the study weighted age-specific increases in remaining life expectancy by age-specific population sizes. It considered drug acquisition costs as well as savings and life extension costs from eliminating cancer. All cancer drugs that underwent a mandatory early benefit assessment in Germany between 2011 and 2015/16 and were granted an added benefit were included. Data on age- and gender-specific probabilities of survival, population sizes, causes of death, and health expenditures, as well as data on cancer costs were taken from the German Federal Office of Statistics and the German Federal Social Insurance Office. RESULTS: Based on the cause-elimination life-table approach and accounting for the age structure of the German population, curing cancer in Germany yields an increase in average remaining life expectancy by 2.66 life years. Based on the current incremental cost-effectiveness ratio of new cancer drugs, which is on average €101,493 per life year gained (€39,751/0.39 life years), the German social health insurance would need to pay €280,497 per insuree to eliminate cancer. Dividing this figure by current average remaining lifetime health expenditures yields a ratio of 2.07, which represents a multiplier of current health expenditures. CONCLUSIONS: Eliminating cancer at current price levels would more than triple total health expenditures in Germany. As the current price of a cure requires a drastic reduction of non-health consumption, it appears that current prices for cancer drugs already on the market (i.e., small steps towards a cure) need careful reconsideration.

How Many Intensive Care Beds are Justifiable for Hospital Pandemic Preparedness? A Cost-effectiveness Analysis for COVID-19 in Germany.

INTRODUCTION: Germany is experiencing the second COVID-19 pandemic wave. The intensive care unit (ICU) bed capacity is an important consideration in the response to the pandemic. The purpose of this study was to determine the costs and benefits of maintaining or expanding a staffed ICU bed reserve capacity in Germany. METHODS: This study compared the provision of additional capacity to no intervention from a societal perspective. A decision model was developed using, e.g. information on age-specific fatality rates, ICU costs and outcomes, and the herd protection threshold. The net monetary benefit (NMB) was calculated based upon the willingness to pay for new medicines for the treatment of cancer, a condition with a similar disease burden in the near term. RESULTS: The marginal cost-effectiveness ratio (MCER) of the last bed added to the existing ICU capacity is €21,958 per life-year gained assuming full bed utilization. The NMB decreases with an additional expansion but remains positive for utilization rates as low as 2%. In a sensitivity analysis, the variables with the highest impact on the MCER were the mortality rates in the ICU and after discharge. CONCLUSIONS: This article demonstrates the applicability of cost-effectiveness analysis to policies of hospital pandemic preparedness and response capacity strengthening. In Germany, the provision of a staffed ICU bed reserve capacity appears to be cost-effective even for a low probability of bed utilization.

Cost Effectiveness of Secukinumab Versus Other Biologics and Apremilast in the Treatment of Active Psoriatic Arthritis in Germany.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The cost effectiveness of secukinumab in PsA has not been evaluated in Germany. OBJECTIVE: The purpose of this study was to conduct a cost-utility analysis of secukinumab in three adult populations with active PsA in Germany: biologic naïve without moderate or severe plaque psoriasis, biologic naïve with moderate or severe plaque psoriasis, and biologic experienced. Comparators included other disease-modifying antirheumatic drugs (DMARDs), including biosimilar versions as well as standard of care. METHODS: The analysis took the viewpoint of the German statutory health insurance. We adapted a decision analytic semi-Markov model to evaluate the cost effectiveness of secukinumab over a lifetime horizon. Treatment response was assessed based on PsA Response Criteria at 12 weeks. Nonresponders or patients discontinuing the initial-line DMARD were allowed to switch to subsequent-line DMARDs. Model input parameters (Psoriasis Area Severity Index, Health Assessment Questionnaire (HAQ), withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and official reports. Health benefits were expressed as quality-adjusted life-years. An annual discount rate of 3% was applied to costs and benefits. The robustness of the study findings was evaluated via sensitivity analyses. RESULTS: In the biologic-naïve population without moderate or severe plaque psoriasis, secukinumab 150 mg either strictly dominated other DMARDs (certolizumab pegol, golimumab, and ustekinumab) or yielded favorable incremental cost-effectiveness ratios (ICERs) (vs. etanercept, adalimumab, and infliximab). In the biologic-naïve population with concomitant moderate to severe plaque psoriasis and in the biologic-experienced population, secukinumab 300 mg was more effective and had a lower ICER than other DMARDs, thus leading to extended dominance. Deterministic sensitivity analyses indicated that the results were most sensitive to the discount rate for costs and health outcomes as well as the HAQ score as an input to utility values. CONCLUSIONS: Secukinumab appears to be cost effective compared with other DMARDs for the treatment of active PsA in biologic-naïve and biologic-experienced populations in Germany.

Budget impact analysis of drugs for ultra-orphan non-oncological diseases in Europe.

BACKGROUND/AIM: Ultra-orphan diseases (UODs) have been defined by a prevalence of less than 1 per 50,000 persons. However, little is known about budget impact of ultra-orphan drugs. METHODS: For analysis, the budget impact analysis (BIA) had a time horizon of 10 years (2012-2021) and a pan-European payer's perspective, based on prevalence data for UODs for which patented drugs are available and/or for which drugs are in clinical development. RESULTS: A total of 18 drugs under patent protection or orphan drug designation for non-oncological UODs were identified. Furthermore, 29 ultra-orphan drugs for non-oncological diseases under development that have the potential of reaching the market by 2021 were found. Total budget impact over 10 years was estimated to be €15,660 and €4965 million for approved and pipeline ultra-orphan drugs, respectively (total: €20,625 million). CONCLUSION: The analysis does not support concerns regarding an uncontrolled growth in expenditures for drugs for UODs.

Determining the price for pharmaceuticals in Germany: comparing a shortcut for IQWiG's efficiency frontier method with the price set by the manufacturer for ticagrelor.

Under the recently enacted pharmaceutical price and reimbursement regulation in Germany, manufacturers and payers negotiate an appropriate reimbursement price for new products. If one of the parties involved wishes so, a formal evaluation of costs and benefits will be conducted by the Institute for Quality and Efficiency in Health Care (IQWiG). IQWiG makes recommendations for a reimbursement price based on the 'efficiency frontier' in a therapeutic area. The analysis requires, when applicable, to calculate savings in other areas of the healthcare system (cost offsets) and healthcare costs during the years of life gained (i.e., downstream costs). A recent paper described the conditions under which calculation of downstream costs is not required. The purpose of this study is to use the drug ticagrelor as an example to demonstrate this shortcut for the efficiency frontier method. The analysis shows that applying the IQWiG approach would result in substantial savings.

Comparing the validity of different measures of illness severity: a hospital-level analysis for acute myocardial infarction.

The aim of the study is to assess the validity of three measures of illness severity (prior year's hospital expenditures, Charlson and Elixhauser indices), by analysing the effect of introducing report cards on hospitals treating patients with acute myocardial infarction (AMI). Medicare claims data were obtained for 1992-1997 for AMI patients aged 65+. We used differences-in-differences regression analysis to assess the impact of report cards introduced in New Jersey and Pennsylvania on the illness severity of AMI patients with and without coronary artery bypass graft (CABG) surgery (relative to states without report cards). The analysis was conducted at the hospital level. For validation we used raw mortality and re-admission trends for AMI patients. While prior hospital expenditures suggest a considerable change in the illness severity of AMI patients in Pennsylvania relative to other states, raw mortality and re-admission trends in Pennsylvania are relatively consistent with the trend in the rest of the USA. In line with raw mortality and re-admission data, the Charlson and Elixhauser indices do not imply a considerable change in the severity of AMI patients in Pennsylvania. For CABG patients, illness severity - as measured by all three severity measurement methods - decreased after introduction of report cards, particularly in Pennsylvania. In conclusion, for AMI patients the Charlson and Elixhauser indices are a more valid measure of illness severity than prior year's hospital expenditures. After report cards were introduced, healthier AMI patients were more likely to receive CABG surgery, while sicker patients were avoided.

Cost-effectiveness of using clinical risk factors with and without DXA for osteoporosis screening in postmenopausal women.

BACKGROUND: According to several guidelines, the assessment of postmenopausal fracture risk should be based on clinical risk factors (CRFs) and bone density. Because measurement of bone density by dual x-ray absorptiometry (DXA) is quite expensive, there has been increasing interest to estimate fracture risk by CRFs. OBJECTIVE: The aim of this study was to determine the cost-effectiveness of osteoporosis screening of CRFs with and without DXA compared with no screening in postmenopausal women in Germany. METHODS: A cost-utility analysis and a budget-impact analysis were performed from the perspective of the statutory health insurance. A Markov model simulated costs and benefits discounted at 3% over lifetime. RESULTS: Cost-effectiveness of CRFs compared with no screening is euro4607, euro21,181, and euro10,171 per quality-adjusted life-year (QALY) for 60-, 70-, and 80-year-old women, respectively. Cost-effectiveness of DXA plus CRFs compared with CRFs alone is euro20,235 for 60-year-old women. In women above the age of 70, DXA plus CRFs dominates CRFs alone. DXA plus CRFs results in annual costs of euro175 million, or 0.4% of the statutory health insurance's annual budget. CONCLUSION: Funders should be careful in adopting a strategy based on CRFs alone instead of DXA plus CRFs. Only if DXA is not available, assessing CRFs only is an acceptable option in predicting a woman's risk of fracture.

A national hypertension treatment program in Germany and its estimated impact on costs, life expectancy, and cost-effectiveness.

Almost 15 million Germans may suffer from untreated hypertension. The purpose of this paper is to estimate the cost-effectiveness of a national hypertension treatment program compared to no program. A Markov decision model from the perspective of the statutory health insurance (SHI) was built. All data were taken from secondary sources. The target population consists of hypertensive male and female patients at high or low risk for cardiovascular events at different age groups (40-49, 50-59, and 60-69 years). The analysis shows fairly moderate cost-effectiveness ratios even for low-risk groups (less than 12,000 euros per life year gained). In women at high risk antihypertensive treatment even leads to savings. This suggests that a national hypertension treatment program provides good value for money. Given the considerable costs of the program itself, any savings from avoiding long-term consequences of hypertension are likely to be offset, however.

European comparison of costs and quality in the treatment of acute back pain.

STUDY DESIGN: Retrospective multicenter observational study. OBJECTIVES: To compare the outpatient quality and costs of treating acute back pain in England, Germany, the Netherlands, and Switzerland. SUMMARY OF BACKGROUND DATA: No study has yet attempted to compare the quality, costs, and resource utilization of acute back pain treatment in Europe. METHODS: A total of 130 randomly selected physician practices assessed services for 1 hypothetical average patient during the first 4 weeks of treatment (cost evaluation) and 127 practices reported retrospective data on 1 real patient (quality evaluation) in 2001. Reimbursement fees served as unit costs for Germany and Switzerland. Average reimbursement fees were used to measure resource utilization in all countries. Quality of care was assessed in terms of the following unnecessary treatments and diagnoses: bed rest for more than 2 days; exercise therapy; scheduling of a radiograph or other imaging tests; and referral to another provider. Responses were weighted with the level of scientific evidence for overuse. RESULTS: Weighted-average overuse ranged from 18% in the Netherlands to 31% in Germany. In England, Germany, and Switzerland, at least a third of the resources used to treat back pain were wasted. CONCLUSIONS: There was considerable waste in treating acute back pain. The Netherlands had highest quality and lowest resource utilization in providing treatment for acute back pain.

Direct costs of care in germany for children and adolescents with diabetes mellitus in the early course after onset.

BACKGROUND AND OBJECTIVE: Prospective population-based cost-of-illness study to evaluate diabetes mellitus (DM)-related direct costs in German pediatric DM care in the early course after onset (perspective: statutory health insurers). PATIENTS AND METHODS: 573 patients with DM <15 years of age were followed for up to 2 years after onset. DM-related hospitalization and ambulatory care, insulin and self-testing regimen were ascertained. Costs per patient-year were estimated (2000 prices). Using multivariate regression, associations between costs and families' socioeconomic status was evaluated. RESULTS: Mean total costs per patient-year were 7,069 euro (interquartile range 5,414-8,127). Onset hospitalization accounted for the majority of costs (4,908 euro, 3,728-6,213). Within post-onset costs, most were attributable to blood glucose self measurement and hospitalization (36% and 32%). Costs were significantly higher in children from families with lower compared to highest educated parents and in children from non-German families (p <0.01). CONCLUSIONS: Among the direct medical costs of childhood DM in the early course after onset, the greatest economic burden was due to hospitalization, in particular at onset. Blood glucose self measurement accounted for the majority of the post-onset costs. Costs were associated with the socio-economic status. It is recommended to evaluate the cost-effectiveness of outpatient programs targeting children from families with lower social status.

Cost-effectiveness analysis of different screening procedures for type 2 diabetes: the KORA Survey 2000.

OBJECTIVE: To compare the cost-effectiveness of different type 2 diabetes screening strategies using population-based data (KORA Survey; Augsburg, Germany; subjects aged 55-74 years), including participation data. RESEARCH DESIGN AND METHODS: The decision analytic model, which had a time horizon of 1 year, used the following screening strategies: fasting glucose testing, the oral glucose tolerance test (OGTT) following fasting glucose testing in impaired fasting glucose (IFG) (fasting glucose + OGTT), OGTT only, and OGTT if HbA(1c) was >5.6% (HbA(1c) + OGTT), all with or without first-step preselection (p). The main outcome measures were costs (in Euros), true-positive type 2 diabetic cases, incremental cost-effectiveness ratios (ICERs), third-party payers, and societal perspectives. RESULTS: After dominated strategies were excluded, the OGTT and HbA(1c) + OGTT from the perspective of the statutory health insurance remained, as did fasting glucose + OGTT and HbA(1c) + OGTT from the societal perspective. OGTTs (4.90 per patient) yielded the lowest costs from the perspective of the statutory health insurance and fasting glucose + OGTT (10.85) from the societal perspective. HbA(1c) + OGTT was the most expensive (21.44 and 31.77) but also the most effective (54% detected cases). ICERs, compared with the next less effective strategies, were 771 from the statutory health insurance and 831 from the societal perspective. In the Monte Carlo analysis, dominance relations remained unchanged in 100 and 68% (statutory health insurance and societal perspective, respectively) of simulated populations. CONCLUSIONS: The most effective screening strategy was HbA(1c) combined with OGTT because of high participation. However, costs were lower when screening with fasting glucose tests combined with OGTT or OGTT alone. The decision regarding which is the most favorable strategy depends on whether the goal is to identify a high number of cases or to incur lower costs at reasonable effectiveness.

[At what time is a reduction of medical under- or overtreatment sensible? Treatment of acute depression as an example]. / Wann lohnt sich der Abbau medizinischer Unter- und Uberversorgung? Das Beispiel der Behandlung akuter Depressionen.

OBJECTIVE: 1) To portray the mathematical relationship between the size of an underuse or overuse problem caused by non-compliance of health professionals and the cost-effectiveness of a quality improvement program; 2) to demonstrate the applicability of the models to a real-world problem (underuse and overuse in the treatment of major depression) and to stress the importance of the costs of a quality improvement program using this example. METHODS: Mathematical formulation of the relationship between the costs of a quality improvement program and the degree of underuse and overuse. RESULTS: The example of reducing underuse in the treatment of major depression shows that an intervention with a favorable cost-effectiveness ratio may be economically unattractive if a quality improvement program incurs high costs secondary to a small quality deficit. The application example also shows that reducing treatment overuse is inefficient if overuse is small and hence the costs of a quality improvement program are higher than the costs of overuse. CONCLUSIONS: The explicit consideration of the size of an underuse or overuse problem in the cost-effectiveness ratio of a quality improvement program may contribute to a more efficient use of health care resources.