From Health to Well-Being: Toward a Monetary Valuation of a Well-Being-Adjusted Life-Year.

OBJECTIVES: Economic evaluations using broader measures to capture benefits beyond improved health can inform policy making, but only if the monetary value of gains measured using these instruments is understood. This study explored contingent valuation as a method to estimate the monetary value of a well-being-adjusted life-year (WALY) as measured by ICEpop Capability Measure for Adults (ICECAP-A). METHODS: In a large online survey of representative samples from 7 European countries, participants valued a change in the ICECAP-A from their current health state to a randomly assigned hypothetical state. Participants were instructed that an unspecified treatment could avoid a loss or produce a gain in well-being and were asked for their willingness to pay (WTP) for this treatment. WTP per WALY was calculated using an aggregated approach that used ICECAP-A tariffs from the United Kingdom. RESULTS: We analyzed a sample of 7428 observations, focusing on avoided losses (n = 6002) because the results for gains were not theoretically valid. Different cutoff points for a marginal change were explored. Depending on the definition of a marginal change, WTP per WALY averaged between €13 323.28 and €61 375.63 for avoided losses between [0, 0.5] and [0, 0.1], respectively, for 1 month. Mean WTP per WALY varied across the countries as follows: Denmark (€17 867.93-€88 634.14), France (€10 278.35-€45 581.28), Germany (€12 119.39-€54 566.56), Italy (€11 753.69-€52 161.25), The Netherlands (€14 612.88-€58 951.74), Spain (€11 904.12-€57 909.17), and United Kingdom (€13 133.75-€68 455.85). CONCLUSION: Despite the inherent limitations of our study, it offers valuable insights into methods for eliciting the WTP for changes in capability well-being as measured with ICECAP-A.

Harmonizing regulatory market approval of products with high safety requirements: Evidence from the European pharmaceutical market.

We causally analyzed whether being a member of the European Union (EU) and having access to a centralized marketing authorization procedure (centralized procedure [CP]) affects availability and time to launch of new pharmaceuticals. We employed multiple difference-in-differences models, exploiting the eastern enlargement of the EU as well as changes in the indications that fall within the compulsory or voluntary scope of the CP. Results showed that countries experienced a mean decrease in launch delay of 10.9 months (p = 0.004) after joining the EU. Effects were higher among pharmaceuticals that belong to indications that might voluntarily participate in the CP but are not obliged to. These are often financially less attractive to manufacturers than pharmaceuticals within the compulsory scope. Availability of new pharmaceuticals launched remained unaffected. We found signs that the magnitude of the country-specific effect of centralized marketing authorization on launch delay may be influenced by strategic decisions of manufacturers at the national level (e.g., parallel trade or reference pricing).

Treatment patterns of individualized real-life tapering approaches based on shared decision-making in rheumatoid arthritis.

OBJECTIVE: To provide real-world evidence on patient-individual tapering patterns of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: Data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021 were analyzed. Participants consist of RA patients in sustained remission who were eligible for DMARD tapering at enrolment. Data from RA patients who experienced tapering of DMARDs at least once during the observational period (n = 200) were used. Descriptive analyses of medical outcomes at baseline and at time of first tapering, time to first tapering, tapering patterns by substance group, and tapering intensity were documented. RESULTS: We did not observe meaningful differences in either disease activity or quality of life measures between substance groups at enrolment, time of first tapering, and at 6 or 12 months after tapering. Median time until first tapering varied between substance groups (csDMARDs: 108 days; bDMARDs: 189 days; combination: 119 days). Most patients received one iteration of tapering only (147/200 patients, 73.5%). Dose reduction was applied for patients treated with csDMARDs (79/86 patients, 91.8%), spacing of interval was the most frequent strategy for patients treated with bDMARDs only (43/48 patients, 89.5%). Necessity for increased DMARD dosage was observed in only 10% of patients (20/200). Tapering intensity by substance was overall heterogenous, indicating high individualization. CONCLUSION: We identify highly heterogeneous tapering patterns between substance groups and within substances. Identification and recognition of patient-individual approaches of tapering will help to further improve the management of RA for both patients and rheumatologists.

Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting.

OBJECTIVE: We aim to provide real-world evidence on the effectiveness of patient-individual tapering of DMARDs for patients with RA in daily clinical practice using medical records and claims data. METHODS: We utilize data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021. Participants consist of RA patients in sustained remission (>6 months) who were eligible for tapering at enrolment. Patients treated with individual tapering based on shared decision making (n = 200) are compared with patients without any dose reduction (n = 237). The risk of loss of remission and the risk of flare is assessed with risk-adjusted Kaplan-Meier estimators and Cox regressions. We evaluate differences in costs 1 year before and after baseline based on claims data for the subgroup of patients insured at one major sickness fund in Germany (n = 76). RESULTS: The risk of flare (hazard ratio 0.88, 95% CI 0.59, 1.30) or loss of remission (hazard ratio 1.04, 95% CI 0.73, 1.49) was not statistically different between the individual tapering group and the continuation group. Minor increases of disease activity and decreases of quality of life were observed 12 months after baseline, again with no statistically significant difference. Drug costs decreased by 1017€ in the individual tapering group while they increased by 1151€ in the continuation group (P < 0.01). CONCLUSION: Individual tapering of DMARDs does not increase the average risk of experiencing flares or loss of remission. Encouraging rheumatologists and patients to apply tapering in shared decision making may be a feasible approach to allow individualization of treatment in RA.

Cost-utility analysis of early versus delayed endovascular intervention in critical limb-threatening ischemia patients with rest pain.

OBJECTIVE: The prevalence of chronic limb-threatening ischemia (CLTI) and poor health outcomes are high in Germany. Serious consequences of CLTI such as amputation and mortality can be effectively prevented by the early use of evidence-based therapeutic measures such as endovascular intervention. We have developed a cost-utility analysis to compare endovascular intervention with bare metal stents (BMSs) and endovascular intervention after conservative treatment from the German payer perspective. METHODS: A Markov model, with a 5-year time horizon and seven states, was developed: (1) intervention, (2) stable 1, (3) major amputation, (4) reintervention, (5) stable 2, (6) care, and (7) all-cause death. Transition probabilities were obtained by pooling the outcomes from multiple clinical studies. The costs were estimated using data from the German diagnosis-related group system, the German rehabilitation fund, and related literature. Health-state utilities were obtained from the reported data. The primary outcomes were the quality-adjusted life-years (QALYs) and costs. RESULTS: Early BMS intervention after 5 years resulted in a cost of €23,913 and an increase of 2.5 QALYs per patient, and endovascular intervention with BMS after conservative treatment after 5 years resulted in a cost of €18,323 and an increase of 2 QALYs per patient. The incremental cost-effectiveness ratio was €12,438. The number of major amputations was reduced by 6%. The results of the structural, deterministic, and probabilistic sensitivity analyses were robust. CONCLUSIONS: Early endovascular intervention with BMS resulted in more QALYs and a reduced risk of major amputation for early-stage CLTI patients. Our results showed that early endovascular intervention is very cost-effective according to World Health Organization recommended cost-effectiveness thresholds. However, the clinical decision regarding the use of early endovascular intervention should be determined by individual patient-level eligibility and the physician's judgment.

Health-related quality of life in seven European countries throughout the course of the COVID-19 pandemic: evidence from the European COvid Survey (ECOS).

PURPOSE: To investigate health-related quality of life (HRQoL) over the course of the COVID-19 pandemic in seven European countries and its association with selected sociodemographic as well as COVID-19-related variables. METHODS: We used longitudinal data from nine quarterly waves collected between April 2020 and January 2022 (sample size per wave ranging from N = 7025 to 7300) of the European COvid Survey (ECOS), a representative survey of adults in Germany, United Kingdom, Denmark, Netherlands, France, Portugal and Italy. HRQoL was measured using the EQ-5D-5L. The association of self-reported COVID-19 infection, perceived health risk from COVID-19, selected sociodemographic variables and the COVID-19 stringency index with HRQoL was analyzed by logistic and linear fixed effects regressions. RESULTS: On average across all nine waves, the proportion of respondents reporting any problems in at least one of the EQ-5D dimensions ranged between 63.8% (Netherlands) and 71.0% (Denmark). Anxiety/depression was the most frequently affected EQ-5D dimension in four countries (Portugal: 52.0%; United Kingdom: 50.2%; Italy: 49.2%; France: 49.0%), whereas pain/discomfort ranked first in three countries (Denmark: 58.3%; Germany: 55.8%; Netherlands: 49.0%). On average across all nine waves, the EQ-VAS score ranged from 70.1 in the United Kingdom to 78.4 in Portugal. Moreover, the EQ-5D-5L index ranged from .82 in Denmark to .94 in France. The occurrence of COVID-19 infection, changes in the perceived risk to one's own health from COVID-19, the occurrence of income difficulties and an increase in the COVID-19 stringency index were associated with increased likelihood of problems in EQ-5D dimensions, reduced EQ-VAS score and reduced EQ-5D-5L index. CONCLUSIONS: Across seven European countries, we found large proportions of respondents reporting problems in HRQoL dimensions throughout the pandemic, especially for anxiety/depression. Various sociodemographic and COVID-19-related variables were associated with HRQoL in longitudinal analysis.

Changes in launch delay and availability of pharmaceuticals in 30 European markets over the past two decades.

BACKGROUND: The timing of the launch of a new drug is an important factor that determines access for patients. We evaluated patient access to pharmaceuticals in 30 European markets over the past two decades. METHODS: Launch dates were extracted from the IQVIA (formerly IMS) database for 30 European countries for all pharmaceuticals launched internationally between 2000 and 2017. We defined launch delay as the difference between the first international launch date and the corresponding national launch date, and calculated these for each country in our sample over time. Additionally, we ranked countries according to their launch delays and looked at changes in the ranking order over time. Lastly, we determined the availability of new pharmaceuticals in each country, calculating this as the percentage of these pharmaceuticals that were available in each country during a pre-specified interval. RESULTS: There was a clear trend towards a decrease in launch delays across all countries from 2000 (37.2 months) to 2017 (11.8 months). Over the entire observation period, the three fastest launching countries were the Netherlands, Sweden, and Germany, whereas the three slowest were Bosnia-Herzegovina, Serbia, and Turkey. Germany had the highest availability of new pharmaceuticals with 85.7%, followed by the United Kingdom (83.1%) and Norway (82.9%). Countries with the lowest availability of pharmaceuticals were Bosnia-Herzegovina, Serbia, and Latvia. Gross domestic product per capita was negatively correlated with launch delay (-0.67, p < 0.000) and positively correlated with the availability of pharmaceuticals (+ 0.19, p < 0.000). CONCLUSION: Launch delay and the availability of pharmaceuticals varied substantially across all 30 European countries. Using countries with above-average availability and below-average launch delays as a benchmark, stakeholders may discuss or modify current pharmaceutical policy, if needed, to improve access to pharmaceutical care.

Blood donation in times of crisis: Early insight into the impact of COVID-19 on blood donors and their motivation to donate across European countries.

BACKGROUND: In this survey, we aimed to provide early insight into the impact of COVID-19 on blood donors and their motivation to donate during the crisis. STUDY DESIGN AND METHODS: We asked representative samples in 7 European countries (Denmark, France, Germany, Italy, Portugal, the Netherlands and the UK) about their blood donation activity and motivation to donate using an online survey. We analysed donor turnout during the COVID-19 period descriptively and using logistic regression. RESULTS: Of the 7122 people that responded to the survey, 1205 (16·9%) blood donors were identified, with 33·8% donating during the first 4-5 months of the COVID-19 period. We observed that around half of donors donated less than normal. The vast majority of donors that did donate made a special effort to do so in response to COVID-19. The majority of donors were also not aware of their blood being tested for COVID-19 antibodies. Although the perceived risk of infection among all respondents whilst donating blood was relatively low, those who anticipated a high risk of infection were much less likely to donate (OR = 0·540; P-value = 0·006). Furthermore, those that were adherent to COVID guidelines were also less likely to donate (OR = 0·583; P-value = 0·000). DISCUSSION: We suggest that blood collection services consider specialist campaigns that focus on the altruistic motivation of donors during the crisis and that they continue to communicate the additional safety measures in place with the aim of reducing the fear of infection whilst donating blood.

Blood donation and donors: insights from a large German teaching hospital (2008-2017).

BACKGROUND AND OBJECTIVES: The availability of blood and blood products is crucial for the provision of high-quality hospital services. We analyse changes in whole blood donations, donors and their behaviour over 9 years at a large German teaching hospital. MATERIALS AND METHODS: A descriptive analysis using data from over 34 000 donors and 265 000 donations from a large university hospital's blood centre was conducted using data from July 2008 to December 2017. The analysis focussed on (a) whole blood donations and (b) donor characteristics and how they changed over time. We categorized donors into four categories according to their donation activity (First-Time, Highly Active, Active and Reactivated). RESULTS: We observed falling donations over time and that donors donated less frequently. Consequently, we show a downward trend in the number of Highly Active donors, whilst First-Time donors remained stable. We also provide evidence that donors donated well below their capacity and that the blood type of donors appeared to be in line with the wider German donor population. Lastly, we show a sharp drop in the return rates of First-Time donors over time. CONCLUSION: We recommend that Highly Active donors and former Highly Active donors are more carefully considered when planning donor engagement strategies and effort made in (at the very least) maintaining their donation activity. Our results in the context of the literature highlight the need for further research into the changing attitudes towards blood donation and prosocial activities.

The impact of drug quality ratings from health technology assessments on the adoption of new drugs by physicians in Germany.

Payers are increasingly calling for the value of new drugs to be measured explicitly. We analyze how the availability of drug quality ratings by health technology assessment (HTA) agencies affects the adoption of new drugs by physicians in Germany. We combine data from drug quality ratings, promotional spending, and a physician panel. In a latent utility model, time to adoption is specified as a function of quality rating, promotional spending by manufacturers, and physician-specific variables. As expected, drugs with a positive rating were adopted faster (p < 0.001) than those without. However, our results suggest that it was the publication of the quality rating itself that affected adoption. Indeed, before a quality rating was published, drugs that went on to receive a positive quality rating were not adopted significantly faster than drugs that went on to receive a negative quality rating. In contrast, after the publication of the HTA quality rating, drugs with a positive rating were adopted significantly faster than those without (p < 0.05). The per physician value of a positive quality rating was EUR 393.50. Our results suggest that there are returns from HTAs beyond their use in price negotiations.

Correction to: Attitudes of physicians from 10 European countries on adherence and how treatment modalities in ABSSSI affect adherence: results from a Delphi survey.

In the originally published article, the name of the last author was not correct. The name is Paolo Antonio Grossi, which is correctly shown above.

Attitudes of physicians from 10 European countries on adherence and how treatment modalities in ABSSSI affect adherence: results from a Delphi survey.

To explore the attitudes of European physicians on adherence and how treatment modalities impact adherence in complicated forms of soft skin and skin structure infections, now referred as acute bacterial skin and skin structures infections (ABSSSI). After literature review, a questionnaire was prepared. Topics focused on (1) the importance of adherence, (2) the importance of administration regimen on adherence, (3) the importance of drug selection on adherence, (4) the importance of complexity on choice of drug for treatment, (5) the role of adherence in drug resistance, and (6) the role of adherence in administration of long-acting antibiotics (ABs). The questionnaire was administered to 323 European infectious diseases specialists, of whom 74% responded. A modified Delphi method was used to obtain the highest consensus. Results varied by countries. We found a high degree of agreement of the importance of adherence in ABSSSI treatment. Experts agreed that complexity of patient's conditions, drug selection, drug resistance, the type of regimen, and the number of infusions impact adherence. Two items linking oral switching and adherence did not reach consensus. Adherence for ABSSSI therapies appears a crucial factor for therapeutic management and reduces the risk of AB resistance. Among new treatment opportunities, long-acting agents, with their characteristics, may represent an interesting options.

Pharmaceutical Pricing in Germany: How Is Value Determined within the Scope of AMNOG?

OBJECTIVES: To analyze how value is determined within the scope of the German Pharmaceutical Restructuring Act, which came into effect in 2011. METHODS: Using data from all pharmaceuticals that had undergone assessment, appraisal, and price negotiations in Germany before June 30, 2016, we applied generalized linear model regression to analyze the impact of added benefit on the difference between negotiated prices and the prices of comparators. Data were extracted from the Federal Joint Committee's appraisals and price databases. We specified added benefit in various ways. In all models, we controlled for additional criteria such as size of patient population, European price levels, and whether the comparators were generic. RESULTS: Our regression results confirmed the descriptive results, with price premiums reflecting the extent of added benefit as appraised by the Federal Joint Committee. On the substance level, an added benefit was associated with an increase in price premium of 227.2% (P < 0.001) compared with no added benefit. Moreover, we saw increases in price premium of 377.5% (P < 0.001), 90.0% (P < 0.001), and 336.8% (P < 0.001) for added benefits that were "considerable," "minor," and "not quantifiable," respectively. Beneficial effects on mortality were associated with the greatest price premium (624.3%; P < 0.001), followed by such effects on morbidity (174.7%; P < 0.001) and adverse events (93.1%; P = 0.019). CONCLUSIONS: Price premiums, or "value," are driven by health gain, the share of patients benefiting from a pharmaceutical, European price levels, and whether comparators are generic. No statement can be made, however, about the appropriateness of the level of price premiums.

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.

Measuring the relationship between costs and outcomes: the example of acute myocardial infarction in German hospitals.

In this paper, we propose a methodological approach to measure the relationship between hospital costs and health outcomes. We propose to investigate the relationship for each condition or disease area by using patient-level data. We examine health outcomes as a function of costs and other patient-level variables by using the following: (1) two-stage residual inclusion with Murphy-Topel adjustment to address costs being endogenous to health outcomes, (2) random-effects models in both stages to correct for correlation between observation, and (3) Cox proportional hazard models in the second stage to ensure that the available information is exploited. To demonstrate its application, data on mortality following hospital treatment for acute myocardial infarction (AMI) from a large German sickness fund were used. Provider reimbursement was used as a proxy for treatment costs. We relied on the Ontario Acute Myocardial Infarction Mortality Prediction Rules as a disease-specific risk-adjustment instrument. A total of 12,284 patients with treatment for AMI in 2004-2006 were included. The results showed a reduction in hospital costs by €100 to increase the hazard of dying, that is, mortality, by 0.43%. The negative association between costs and mortality confirms that decreased resource input leads to worse outcomes for treatment after AMI.

Mapping from SIBDQ to EQ-5D-5L for patients with inflammatory bowel disease.

OBJECTIVE: Clinical studies commonly use disease-specific measures to assess patients' health-related quality of life. However, economic evaluation often requires preference-based utility index scores to calculate cost per quality-adjusted life-year (QALY). When utility index scores are not directly available, mappings are useful. To our knowledge, no mapping exists for the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Our aim was to develop a mapping from SIBDQ to the EQ-5D-5L index score with German weights for inflammatory bowel disease (IBD) patients. METHODS: We used 3856 observations of 1055 IBD patients who participated in a randomised controlled trial in Germany on the effect of introducing regular appointments with an IBD nurse specialist in addition to standard care with biologics. We considered five data availability scenarios. For each scenario, we estimated different regression and machine learning models: linear mixed-effects regression, mixed-effects Tobit regression, an adjusted limited dependent variable mixture model and a mixed-effects regression forest. We selected the final models with tenfold cross-validation based on a model subset and validated these with observations in a validation subset. RESULTS: For the first four data availability scenarios, we selected mixed-effects Tobit regressions as final models. For the fifth scenario, mixed-effects regression forest performed best. Our findings suggest that the demographic variables age and gender do not improve the mapping, while including SIBDQ subscales, IBD disease type, BMI and smoking status leads to better predictions. CONCLUSION: We developed an algorithm mapping SIBDQ values to EQ-5D-5L index scores for different sets of covariates in IBD patients. It is implemented in the following web application: https://www.bwl.uni-hamburg.de/hcm/forschung/mapping.html .

Inflammatory bowel disease (IBD) patients with impaired quality of life on biologic therapy benefit from the support of an IBD nurse specialist: Results of a randomised controlled trial in Germany (IBDBIO-ASSIST study).

BACKGROUND: IBDBIO-ASSIST was a randomised controlled trial assessing the efficacy of care provided by IBD nurse specialists in Germany in improving health-related quality of life (QoL) in IBD patients on biologic therapy. AIM: To evaluate patient-related outcomes and economic consequences associated with integrating IBD nurses into usual care. METHODS: We randomly assigned 1086 patients with IBD on biologic therapy to a control group (CG) receiving usual care or an intervention group (IG) receiving additional care from an IBD nurse specialist. The primary outcome was disease-specific QoL (sIBDQ) assessed at 6, 12 and 18 months. RESULTS: At baseline, patients in both groups were highly satisfied with their treatment situation and had relatively high sIBDQ values (range: 1-7; CG: 5.12; IG: 4.92). In the intention-to-treat (ITT) analysis of the overall sample, there was no significant difference in sIBDQ between groups at the assessment time points. However, a per-protocol analysis of patients with impaired QoL at baseline (EQ-VAS < 75 [median]), showed improvement in sIBDQ over 6 months that became significant at month 12 and remained significant through month 18 (baseline: IG 4.24; CG 4.31; 18 months: IG 5.02; CG 4.76; p = 0.017). CONCLUSION: High baseline satisfaction of IBD patients with treatment and the relatively high baseline sIBDQ values may have contributed to the lack of significant difference in sIBDQ scores for the overall sample. However, patients with impaired QoL derived significant benefit from additional care provided by an IBD nurse specialist, leading to meaningful improvements in sIBDQ over the long term.

Does health technology assessment compromise access to pharmaceuticals?

In response to rapidly rising pharmaceutical costs, many countries have introduced health technology assessment (HTA) as a 'fourth hurdle'. We evaluated the causal effect of HTA based regulation on access to pharmaceuticals by using the introduction of Germany's HTA system (AMNOG) in 2011. We obtained launch data on pharmaceuticals for 30 European countries from the IQVIA (formerly IMS) database. Using difference-in-difference models, we estimated the effect of AMNOG on launch delay, the ranking order of launch delays, and the availability of pharmaceuticals. We then compared the results for Germany to Austria, Czechia, Italy, Portugal, and the UK. Across all six countries, launch delays decreased from the pre-AMNOG period (25.01 months) to the post-AMNOG period (14.34 months). However, the introduction of AMNOG consistently reduced the magnitude of the decrease in launch delay in Germany compared to the comparator countries (staggered DiD: + 4.31 months, p = 0.05). Our logit results indicate that the availability of pharmaceuticals in Germany increased as a result of AMNOG (staggered logit: + 5.78%, p = 0.009). We provide evidence on the trade-off between regulation and access. This can help policymakers make better-informed decisions to strike the right balance between cost savings achieved through HTA based regulation and access to pharmaceuticals.

Does health technology assessment compromise access to pharmaceuticals?

In response to rapidly rising pharmaceutical costs, many countries have introduced health technology assessment (HTA) as a 'fourth hurdle'. We evaluated the causal effect of HTA based regulation on access to pharmaceuticals by using the introduction of Germany's HTA system (AMNOG) in 2011. We obtained launch data on pharmaceuticals for 30 European countries from the IQVIA (formerly IMS) database. Using difference-in-difference models, we estimated the effect of AMNOG on launch delay, the ranking order of launch delays and the availability of pharmaceuticals. We then compared the results for Germany to Austria, Czechia, Italy, Portugal and the UK. Across all six countries, launch delay decreased from the pre-AMNOG period (25.01 months) to the post-AMNOG period (14.34 months). However, the introduction of AMNOG consistently reduced the magnitude of the decrease in launch delay in Germany compared to the comparator countries (staggered DiD: + 4.31 months, p = 0.05). Our logit results indicate that the availability of pharmaceuticals in Germany increased as a result of AMNOG (staggered logit: + 5.78%, p = 0.009). We provide evidence on the trade-off between regulation and access. This can help policymakers make better informed decisions to strike the right balance between cost savings achieved through HTA based regulation and access to pharmaceuticals.

10 Years of AMNOG: What is the Willingness-to-Pay for Pharmaceuticals in Germany?

OBJECTIVES: The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are conducted based on evidence-based medical benefit assessments using data from prior clinical trials. Although the act does not explicitly set a willingness-to-pay (WTP) threshold, the process itself implicitly establishes a WTP for health improvement. We evaluated the implicit WTP for prescription pharmaceuticals post-AMNOG in the German healthcare system from the decision-maker/payer perspective. METHODS: We extracted data on patient-group-specific annual treatment costs and endpoints from 2011 to 2021 from the dossiers assessed by the German Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss). Using incremental cost-effectiveness ratios (ICERs), we calculated a WTP for the indications (I) diabetes, (II) cardiovascular disease, and (III) psoriasis weighted according to patient group size, first from the perspective of the decision-maker (approach A), and second from the perspective of the industry (approach B). To put clinical outcome measures into relation to one another, minimum clinically important differences (MCIDs) were derived from the literature and compared. RESULTS: The annual treatment costs of newly authorized drugs were substantially higher (both pre- and post-negotiation) than that of their comparators (e.g., psoriasis, pre-negotiation: €20,601.59, post-negotiation: €16,763.57; comparators: €5178.00). However, although newly launched drugs were more expensive than their comparators, they brought greater medical benefits and were more aligned with value (r = 0.59, P < 0.001) than older drugs. We estimated WTP to vary widely by indication group [€33,814.08 per 1 percentage point hemoglobin A1c (HbA1c) reduction for diabetes, €10,970.83 per life year gained for cardiovascular disease, and €663.46 per 1% PASI decrease for psoriasis; approach A]. WTP was converted to MCID thresholds: diabetes: €16,907.04; cardiovascular drugs: no MCID existent to convert; and psoriasis: €33,173.00. WTP remained constant over time for diabetes and cardiovascular drugs but increased for psoriasis drugs. CONCLUSION: This paper is one of the first to estimate the implicit WTP for prescription pharmaceuticals post-AMNOG and suggests that the WTP may vary between different therapeutic areas. Additionally, making different assumptions (approach A versus approach B) with regard to the assumed effectiveness in indication areas that had been declared as having no additional benefit by the FJC may explain the different perspectives of decision-makers and of the pharmaceutical industry on the value of a pharmaceutical.