The HTA-informed Decision-Making by GBA/IQWiG in Germany and NICE in England: The Role of Budget Impact.
Value in Health (2023), DOI: 10.1016/j.jval.2023.02.018 (Pre-proof; online ahead of print).
(Article available on request)
Objectives: The aim of our study was to test (official) evaluation criteria including the potential role of budget impact (BI) on health technology assessment (HTA) outcomes published by the Federal Joint Committee (GBA) and the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany as well as the National Institute for Health and Care Excellence (NICE) in England.
Methods: Data were extracted from all publicly available GBA decisions and IQWiG assessments as well as NICE single technology appraisals (STAs) between January 2011 and June 2018, and information with regard to evaluation criteria used by these agencies was collected. Data were analyzed using logistic regression to estimate the effect of the BI on the HTA outcome(s) while controlling for criteria used by GBA/IQWiG and NICE.
Results: NICE recommendations are largely driven by the incremental cost-effectiveness ratio and, if applicable, by end-of-life criteria (p<.01). While IQWiG assessments are significantly affected by the availability of randomized-controlled trials and patient-relevant endpoints (p<.01), GBA appraisals primarily focus on endpoints (p<.01). The BI correlated with NICE STAs (inverted-U relationship, p<.1) and IQWiG recommendations (increasing linear relationship, p<.05), but not with GBA decisions (p>.1). However, as IQWiG assessments seem to be more rigorous than GBA appraisals regarding the consideration of evidence-based evaluation criteria, decisions by GBA might be negatively associated with the BI.
Conclusions: Results reveal that GBA/IQWiG and NICE follow their official evaluation criteria consistently. After controlling for all significant variables, the BI seems to have an (independent) effect on HTA outcomes as well.
Survival and comorbidities in lung cancer patients: evidence from administrative claims data in Germany.
Oncology Research (2022); 30(4), 173-185. DOI: 10.32604/or.2022.027262.
Lung cancer is the most common cancer type worldwide and has the highest and second highest mortality rate for men and women respectively in Germany. Yet, the role of comorbid illnesses in lung cancer patient prognosis is still debated. We analyzed administrative claims data from one of the largest statutory health insurance (SHI) funds in Germany, covering close to 9 million people (11% of the national population); observation period was from 2005 to 2019. Lung cancer patients and their concomitant diseases were identified by ICD-10-GM codes. Comorbidities were classified according to the Charlson Comorbidity Index (CCI). Incidence, comorbidity prevalence and survival are estimated considering sex, age at diagnosis, and place of residence. Kaplan Meier curves with 95% confidence intervals were built in relation to common comorbidities. We identified 70,698 lung cancer incident cases in the sample. Incidence and survival figures are comparable to official statistics in Germany. Most prevalent comorbidities are
chronic obstructive pulmonary disease (COPD) (36.7%), followed by peripheral vascular disease (PVD) (18.7%), diabetes without chronic complications (17.4%), congestive heart failure (CHF) (16.5%) and renal disease (14.7%). Relative to overall survival, lung cancer patients with CHF, cerebrovascular disease (CEVD) and renal disease are associated with largest drops in survival probabilities (9% or higher), while those with PVD and diabetes without
chronic complications with moderate drops (7% or lower). The study showed a negative association between survival and most common comorbidities among lung cancer patients, based on a large sample for Germany. Further research needs to explore the individual effect of comorbidities disentangled from that of other patient characteristics such as cancer stage and histology.
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Modeling the natural history and screening effects for colorectal cancer using both adenoma and serrated neoplasia pathways: the development, calibration, and validation of a discrete event simulation model.
MDM Policy & Practice (2023); 8(1). DOI: 10.1177/23814683221145701 (Epub ahead of print).
Background. Existing colorectal cancer (CRC) screening models mostly focus on the adenoma pathway of CRC development, overlooking the serrated neoplasia pathway, which might result in overly optimistic screening predictions. In addition, Bayesian inference methods have not been widely used for model calibration. We aimed to develop a CRC screening model accounting for both pathways, calibrate it with approximate Bayesian computation (ABC) methods, and validate it with large CRC screening trials.
Methods. A discrete event simulation (DES) of the CRC natural history (DECAS) was constructed using the adenoma and serrated pathways in R software. The model simulates CRC-related events in a specific birth cohort through various natural history states. Calibration took advantage of 74 prevalence data points from the German screening colonoscopy program of 5.2 million average-risk participants using an ABC method. CRC incidence outputs from DECAS were validated with the German national cancer registry data; screening effects were validated using 17-y data from the UK Flexible Sigmoidoscopy Screening sigmoidoscopy trial and a German screening colonoscopy cohort study.
Results. The Bayesian calibration rendered 1,000 sets of posterior parameter samples. With the calibrated parameters, the observed age- and sex-specific CRC prevalences from the German registries were within the 95% DECAS-predicted intervals. Regarding screening effects, DECAS predicted a 41% (95% intervals 30%–51%) and 62% (95% intervals 55%–68%) reduction in 17-y cumulative CRC mortality for a single screening sigmoidoscopy and colonoscopy, respectively, falling within 95% confidence intervals reported in the 2 clinical studies used for validation.
Conclusions. We presented DECAS, the first Bayesian-calibrated DES model for CRC natural history and screening, accounting for 2 CRC tumorigenesis pathways. The validated model can serve as a valid tool to evaluate the (cost-)effectiveness of CRC screening strategies.
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Estimation of the stage-wise costs of breast cancer in Germany using a modeling approach.
Frontiers in Public Health (2023). DOI: 10.3389/fpubh.2022.946544.
Breast cancer (BC) is a heterogeneous disease representing a substantial economic burden. In order to develop policies that successfully decrease this burden, the factors affecting costs need to be fully understood. Evidence suggests that early-stage BC has a lower cost than a late stage BC. We aim to provide conservative estimates of BC's stage-wise medical costs from German healthcare and the payer's perspective. To this end, we conducted a literature review of articles evaluating stage-wise costs of BC in Germany through PubMed, Web of Science, and Econ Lit databases supplemented by Google Scholar. We developed a decision tree model to estimate BC-related medical costs in Germany using available treatment and cost information. The review generated seven studies; none estimated the stage-wise costs of BC. The studies were classified into two groups: case scenarios (five studies) and two studies based on administrative data. The first sickness funds data study (Gruber et al., 2012) used information from the year 1999 to approach BC attributable cost; their results suggest a range between €3,929 and €11,787 depending on age. The second study (Kreis, Plöthner et al., 2020) used 2011-2014 data and suggested an initial phase incremental cost of €21,499, an intermediate phase cost of €2,620, and a terminal phase cost of €34,513 per incident case. Our decision tree model-based BC stage-wise cost estimates were €21,523 for stage I, €25,679 for stage II, €30,156 for stage III, and €42,086 for stage IV. Alternatively, the modeled cost estimates are €20,284 for the initial phase of care, €851 for the intermediate phase of care, and €34,963 for the terminal phase of care. Our estimates for phases of care are consistent with recent German estimates provided by Kreis et al. Furthermore, the data collected by sickness funds are collected primarily for reimbursement purposes, where the German ICD-10 classification system defines a cancer diagnosis. As a result, claims data lack the clinical information necessary to understand stage-wise BC costs. Our model-based estimates fill the gap and inform future economic evaluations of BC interventions.
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Out-of-pocket payments and loss of income among long-term breast cancer survivors in Germany: a multi-regional population-based study.
Journal of Cancer Survivorship (2022). DOI: 10.1007/s11764-022-01293-x (Epub ahead of print).
This study aims to examine the magnitude of out of pocket (OOP) payments and income loss, as well as to identify socioeconomic and clinical factors among long-term breast cancer (BC) survivors in Germany
We examine data from 2654 long-term BC survivors in Germany that participated in the "CAncEr Survivorship - A multi-Regional population-based study" (CAESAR) and who were at least 5 years post diagnosis. BC-related OOP payments and income loss both within the 12 months prior to the survey were analyzed. Two-part regression models were performed to identify socioeconomic and clinical factors.
OOP payments were incurred by 51.9% of survivors with a total mean spending of 566 euros. Income loss was present among 9.6% of survivors and averaged 5463 euros among those reporting such. Socioeconomic and clinical factors associated with higher OOP payments (p ≤ 0.05) included age at time of diagnosis (65-79 years), education (10-11 years), (early) retirement, stage of diagnosis (stage III), time from diagnosis (more than 10 years), comorbidities (at least 1), and the use of rehabilitation services. Regarding income loss, age at time of diagnosis (50-59 years), (early) retirement, stage of diagnosis (stage II), time from diagnosis (5-7 years), comorbidities (at least 1), and receiving chemotherapy treatment were associated with higher losses.
For some survivors in Germany, financial burden can be considerably high despite comprehensive healthcare and support from social security.
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Income loss after cancer—Results from Germany.
Onkologie (2022), DOI: 10.1007/s00761-022-01243-3 (Epub ahead of print).
(Article available on request)
Krankheitslast von Lungenkrebs in Deutschland: Epidemiologie und Kosten.
Forum (2022), DOI: 10.1007/s12312-022-01123-2 (Epub ahead of print).
(Article available on request)
Krankheitslast von Prostatakrebs in Deutschland: Epidemiologie und Kosten.
Forum (2022), Ausgabe 3/2022.
(Article available on request)
Quality appraisal for systematic literature reviews of health state utility values. A descriptive analysis.
BMC Medical Research Methodology (2022), DOI: 10.21203/rs.3.rs-1589412/v1 (Epub ahead of print on Research Square).
(Article available on request)
Health state utility values (HSUVs) are essential input parameters to cost-utility analysis (CUA). Quality appraisal (QA) of systematic literature reviews (SLRs) of HSUVs is an important process towards the credibility of HSUVs estimates; yet, authors often overlook this crucial process. A scientifically developed and widely accepted QA tool for this purpose is lacking and warranted. Objectives To comprehensively describe the nature of QA in SRLs of HSUVs and generate a list of commonly used items. A comprehensive literature search was conducted in PubMed from 01.01.2015 to 15.05.2021. SLRs of empirical studies of HSUVs that were published in English were included. Descriptive data, including QA tools checklists or good practice recommendations used or cited, items used, and methods of incorporating QA results into study findings were extracted and comprehensively reviewed. Descriptive statistics (frequencies of use and occurrences of items, acceptance and counterfactual acceptance rates) were computed. A comprehensive list of QA items was generated. A total of 68 SLRs were included, comprising 84 items and 30 QA tools and good recommendation practices. The prevalence of QA was 56% (38/68). Recommendations by NICE and ISPOR guidelines appeared in 42% (16/38) of the SLRs that appraised quality. The most commonly used QA items in SLRs were response rates (26/38), loss of follow up (21/38), statistical analysis (20/38) and sample size (20/38). Yet, the most commonly featured items in QA tools and GPRs were statistical analysis (21/30), confounding or baseline equivalency (20/30), and blinding (14/30). Only 5% of the SLRS used QA to inform the data analysis, with acceptance rates of 100% (in two studies) and 53% and 33%. A mean counterfactual acceptance rate of 55% (median 53% and IQR 56%) was observed. There is a considerably low prevalence of QA in the SLRs of HSUVs. Also, there is wide a variation in the QA dimensions and items included in both SLRs and extracted tools. This underscores the need for a scientifically developed QA tool for multi-variable primary studies of HSUVs.
Economic Burden of Pancreatic Cancer in Europe: a Literature Review.
Journal of Gastrointestinal Cancer (2022). DOI: 10.1007/s12029-022-00821-3 (Epub ahead of print).
Pancreatic cancer is characterized by its high mortality, usually attributed to its diagnosis in already advanced stages. This article aims at presenting an overview of the economic burden of pancreatic cancer in Europe.
A systematic literature review was conducted. It made use of the search engines EconLit, Google Scholar, PubMed and Web of Science, and retrieved articles published after December 31st, 1992, and before April 1st, 2020. Study characteristics and cost information were extracted. Cost per patient and cost per patient per month (PPM) were calculated, and drivers of estimate heterogeneity was analysed. Results were converted into 2019 Euros.
The literature review yielded 26 studies on the economic burden attributable to pancreatic cancer in Europe. Cost per patient was on average 40,357 euros (median 15,991), while figures PPM were on average 3,656 euros (median 1,536). Indirect costs were found to be on average 154,257 euros per patient or 14,568 euros PPM, while direct costs 20,108 euros per patient and 2,004 euros PPM. Nevertheless, variation on cost estimations was large and driven by study methodology, patient sample characteristics, such as type of tumour and cancer stage and cost components included in analyses, such as type of procedure.
Pancreatic cancer direct costs PPM are in the upper bound relative to other cancer types; however, direct per patient costs are likely to be lower because of shorter survival. Indirect costs are substantial, mainly attributed to high mortality.
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Use of the incremental cost effectiveness ratio for decision-making policies - what's the problem? A perspective paper.
Expert Review of Pharmacoeconomics & Outcomes Research (2022), DOI: 10.1080/14737167.2022.2064847 (Epub ahead of print).
(Article available on request)
Drug reimbursement decisions that spark public controversy are potential signals that processes used to reach such decisions do not adequately reflect society's goals. Such controversial decisions appear to be a characteristic of Quality Adjusted Life Year (QALY) based Incremental Cost Effectiveness Ratio (ICER) dominated decision-making systems. QALY based ICER-heavy systems have several known weaknesses that lead to individual and societal preferences being either ignored or considered in an unsystematic and inconsistent fashion.
We reprise some of the key inadequacies of QALY based ICER analyses and suggest there are other means including multi-criteria decision analysis (MCDA) and cost-benefit analysis based on willingness to pay (WTP) measures by which to partially mitigate these weaknesses
For long, the inadequacies of QALY based ICER-heavy decision-making systems have been rationalized with the answer: "while the method is a second best, it is the best we currently have". In light of the equally well developed and widely utilized alternatives available, this resistance to improve assessment processes should not be accepted by policy makers. Health technology assessment bodies should consider and, with appropriate modifications, adopt these alternatives as they have the potential to result in more comprehensive, systematic and accountable decision making.
QALYs In Health Resource Usage Decisions.
Health Aff (Millwood) 2022; 41(4): 609-610. DOI: 10.1377/hlthaff.2021.01926.
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The Value of Freedom: A Review of the Current Developments and Conceptual Issues in the Measurement of Capability.
Journal of Human Development and Capabilities (2022). DOI:10.1080/19452829.2022.2053506 (Epub ahead of print).
In health economics, proponents of the capability approach argue that the value of health improvements should be evaluated us broad domains which reflect the capabilities of an individual. Instruments have been developed to measure these domains. These instruments operationalise the measurement of capability in different ways. The objective of this study is to analyze specifically how instruments operationalise the capability approach.
Using a comprehensive pearl growing search methodology, we identified ten instruments. The content of these instruments was analysed in three stages. First, the definition of capability that was used for the development of an instrument was identified. Then, an analysis was conducted on how this definition was operationalised in the instrument’s development. Lastly, the content of the instruments was compared with the concept “option freedom”, which provides a more comprehensive definition of capability, to study whether the instruments measure capability or other aspects that are relevant for wellbeing assessment.
We conclude that, despite using a shared definition of capability, the instruments differ in their methods to measure capability. Some instruments might miss content that reflect the burdens that people experience while achieving their capabilities in certain contexts. This might be due to the unclear conceptualisation of capability by Sen.
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The Ethics of COVID-19 Vaccine Allocation: Don't Forget the Trade-Offs!
Public Health Ethics; phac001 (2022). DOI: 10.1093/phe/phac001 (Epub ahead of print).
The issue of COVID-19 vaccine allocation is still highly controversial on the international as well as on the national level (particularly in many low- and middle-income countries), and policy-makers worldwide struggle in striking a fair balance between different ethical principles of vaccine allocation, in particular maximum benefit, reciprocity, social justice and equal respect. Any political decision that implements these principles comes at a cost in terms of loss of lives and of loss of life years that could potentially have been prevented by a different vaccination strategy. This article illustrates these trade-offs using quantitative analysis and shows how this approach can contribute to providing a rational and transparent grounding of political decisions on COVID-19 vaccine allocation.
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Evaluating discrete choice experiment willingness to pay [DCE-WTP] analysis and relative social willingness to pay [RS-WTP] analysis in a health technology assessment of a treatment for an ultra-rare childhood disease [CLN2].
Expert Rev Pharmacoecon Outcomes Res. (2022). DOI: 10.1080/14737167.2022.2014324 (Open Access Article).
Conventional cost-effectiveness analysis [CEA] using cost per QALY thresholds may counteract other incentives introduced to foster development of treatments for rare and ultra-rare diseases. Therefore, alternative economic evaluation methods were explored, namely Discrete Choice Experiment Willingness to Pay (DCE-WTP) and Relative Social Willingness to Pay (RS-WTP), to value interventions for an ultra-rare childhood disease, Neuronal Ceroid Lipofuscinosis type 2 (CLN2).
Treatment for CLN2 was valued from a citizen's ('social') perspective using DCE-WTP and RS-WTP in a survey of 4,009 United Kingdom [UK] adults. Three attributes (initial quality of life, treatment effect, and life expectancy) were used in both analyses. For DCE-WTP, a cost attribute (marginal income tax increase) was also included. Optimal econometric models were identified.
DCE-WTP indicated that UK adults are willing to pay incremental increases through taxation for improvements in CLN2 attributes. RS-WTP identified a willingness to allocate >40% of a pre-assigned healthcare budget to prevent child mortality and approximately 15% for improved health status.
Both techniques illustrate substantive social WTP for CLN2 interventions, despite the small number of children benefitting. This highlights a gap between UK citizens' willingness to spend on rare disease interventions and current funding policies.
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The COVID-19 Pandemic and Cancer Patients in Germany: Impact on Treatment, Follow-Up Care, and Psychological Burden.
Frontiers. Public Health 9: 788598 (2022). DOI: 10.3389/fpubh.2021.788598 (Open Access Article).
In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, governments imposed various measures to decrease the rate of disease spread, and health care policy makers prioritized resource allocation to accommodate COVID-19 patients. We conducted a cross-sectional online survey in Germany (July 2020–June 2021) to assess the frequency of changes to cancer care among cancer patients and to explore the psychological impact of the pandemic writ large. Cancer patients who contacted the Cancer Information Service (Krebsinformationsdienst, KID) of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) via email were invited to complete an online questionnaire, capturing demographics, cancer specifics (e.g., type, disease phase, primary place of treatment, etc.), and any changes to their medical, follow-up, psycho-oncological or nursing care. General level of psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS) along with face-validated items regarding worries and social isolation specific to the pandemic. In total, 13% of 621 patients reported a change to their treatment or care plan. Of those patients with changes, the majority of changes were made to follow-up care after treatment (56%), to monitoring during treatment (29%) and to psychological counseling (20%). Of the overall sample, more than half of patients (55%) reported symptoms of anxiety and 39% reported symptoms of depression. Patients with a change in cancer care were more likely to report symptoms of depression than those with no change (AOR: 2.18; 95% CI: 1.26–3.76). Concern about the pandemic affecting the quality of health care was a predictor of both anxiety (AOR: 2.76; 95% CI: 1.75–4.35) and depression (AOR: 2.15; 95% CI: 1.43–3.23). Results showed that the majority of cancer patients in our study did not experience a change in their cancer care. However, the level of anxiety and psycho-social burden of cancer patients during the pandemic was high throughout the study period. Our findings underscore the need for health care services and policy makers to assess and to attend cancer patients' medical needs, with added emphasis on patients' psychological and social well-being. This applies particularly in situations where the healthcare system is strained and prioritization is necessary.
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Fast zwei Jahre Coronapandemie aus der Perspektive von Krebsbetroffenen [Nearly two years of the coronavirus pandemic from the perspective of people affected by cancer].
Onkologe 28, 248–252 (2022). DOI: 10.1007/s00761-022-01096-w (Open Access Article).
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Messung der Kosten von Krebserkrankungen in Deutschland. Teil 2 - Wirtschaftliche Belastung [Determining the cost of cancer in Germany. Part 2 - economic burden].
Forum 37, 42–48 (2022). DOI: 10.1007/s12312-021-01026-8.
(Article available on request)
Health and life insurance-related problems in very long-term cancer survivors in Germany: a population-based study.
Journal of Cancer Research and Clinical Oncology (2022), 148(1), 155–162. DOI: 10.1007/s00432-021-03825-x (Open Access Article).
Limited research suggests that cancer survivors have problems with insurance. Our study aimed to gain insight into the proportion of very long-term (14-24 years post-diagnosis) survivors of breast, colorectal, and prostate cancers who had problems with health (HI) and life (LI) insurance.
We used data from CAESAR (CAncEr Survivorship-A multi-Regional population-based study). Participants completed questions on change in insurance providers since cancer diagnosis, problems with requesting (additional) HI or LI, and how potential problems were resolved. We conducted logistic regression to determine factors associated with change in statutory HI.
Of the 2714 respondents, 174 (6%) reported having changed HI providers. Most switched between different statutory HI providers (86%), 9% from statutory to private, and 5% from private to statutory. Respondents who changed statutory HI providers were more likely to be prostate cancer survivors (OR 2.79, 95% CI 1.01-7.68) while being ≥ 65 years at time of diagnosis (OR 0.58, 95% CI 0.35-0.96) and having ≥ 2 comorbid conditions (OR 0.61, 95% CI 0.40-0.92) were associated with reduced odds for change. Problems in changing HI were minimal and were resolved with additional contribution. Of the 310 respondents who tried to get LI, 25 respondents reported having difficulties, of whom the majority had their request rejected.
Most cancer survivors did not change their HI nor tried to buy LI after cancer diagnosis. Problems with changing statutory HI were generally resolved with additional contribution while the main problem encountered when buying LI was rejection of request.
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Messung der Kosten von Krebserkrankungen in Deutschland. Teil 1 - Epidemiologie und Krankheitslast [Determining the cost of cancer in Germany. Part 1 - epidemiology and disease burden].
Forum 36, 406–410 (2021). DOI: 10.1007/s12312-021-00988-z.
(Article available on request)
Health technology assessment (HTA) in England, France and Germany: What do matched drug pairs tell us about recommendations by national HTA agencies?
J Comp Eff Res (2021). DOI: 10.2217/cer-2021-0047 (Epub ahead of print).
To explore health technology assessment (HTA) outcomes of matched drug pairs by national agencies in Germany (Gemeinsamer Bundesausschuss, GBA), France (Haute Autorité de Santé, HAS) and England and Wales (NICE).
We considered published GBA decisions, HAS reports and NICE guidance from January 2011 to June 2018. HTAs of matched pairs were compared overall, and for non-cancer and cancer drugs separately. We further analyzed the role of additional attributes related to cancer therapies.
Matched pairs show higher concordance for GBA/HAS than for GBA/NICE and HAS/NICE. Overall, NICE evaluated technologies more favorably than GBA and HAS. GBA appraisals of cancer drugs, however, tended to be more positive than cancer-related recommendations by NICE and HAS.
The findings indicate substantial variations in HTAs, although cancer-related outcomes seem to diverge less than non-cancer results.
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Resource allocation in the Covid-19 health crisis: are Covid-19 preventive measures consistent with the Rule of Rescue?
Medicine, Health Care and Philosophy (2021). DOI: 10.1007/s11019-021-10045-0 (Epub ahead of print).
The Covid-19 pandemic has led to a health crisis of a scale unprecedented in post-war Europe. In response, a large amount of healthcare resources have been redirected to Covid-19 preventive measures, for instance population-wide vaccination campaigns, large-scale SARS-CoV-2 testing, and the large-scale distribution of protective equipment (e.g., N95 respirators) to high-risk groups and hospitals and nursing homes. Despite the importance of these measures in epidemiological and economic terms, health economists and medical ethicists have been relatively silent about the ethical rationales underlying the large-scale allocation of healthcare resources to these measures. The present paper seeks to encourage this debate by demonstrating how the resource allocation to Covid-19 preventive measures can be understood through the paradigm of the Rule of Rescue, without claiming that the Rule of Rescue is the sole rationale of resource allocation in the Covid-19 pandemic.
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How Much Does It Cost to Research and Develop a New Drug? A Systematic Review and Assessment.
PharmacoEconomics (2021). DOI: 10.1007/s40273-021-01065-y (Epub ahead of print).
Debate over the viability of the current commercial research and development (R&D) model is ongoing. A controversial theme is the cost of bringing a new molecular entity (NME) to market.
Our aim was to evaluate the range and suitability of published R&D cost estimates as to the degree to which they represent the actual costs of industry.
We provided a systematic literature review based on articles found in the Pubmed, Embase and EconLit electronic databases, and in a previously published review. Articles published before March 2020 that estimated the total R&D costs were included (22 articles with 45 unique cost estimates). We included only literature in which the methods used to collect the information and to estimate the R&D costs were clearly described; therefore, three reports were excluded. We extracted average pre-launch R&D costs per NME and converted the values to 2019 US dollars (US$) using the gross domestic product (GDP) price deflator. We appraised the suitability of the R&D estimated costs by using a scoring system that captures three domains: (1) how success rates and development time used for cost estimation were obtained; (2) whether the study considered potential sources contributing to the variation in R&D costs; and (3) what the components of the cost estimation were.
Estimates of total average capitalized pre-launch R&D costs varied widely, ranging from $161 million to $4.54 billion (2019 US$). Therapeutic area-specific estimates were highest for anticancer drugs (between $944 million and $4.54 billion). Our analysis identified a trend of increasing R&D costs per NME over time but did not reveal a relation between cost estimates and study ranking when the suitability scores were assessed. We found no evidence of an increase in suitability scores over time.
There is no universally correct answer regarding how much it costs, on average, to research and develop an NME. Future studies should explicitly address previously neglected variables, which likely explain some variability in estimates, and consider the trade-off between the transparency and public accessibility of data and their specificity. Use of our proposed suitability scoring system may assist in addressing such issues.
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Do certified cancer centers provide more cost-effective care? A health economic analysis of colon cancer care in Germany using administrative data.
International Journal of Cancer (2021). DOI: 10.1002/ijc.33728 (Epub ahead of print).
Hospital certification has become an important measure to improve cancer care quality, with the potential effect of prolonging patient survival and reducing medical spending. However, yet to be explored is the cost-effectiveness of cancer care provided in certified hospitals, considering significant additional costs incurred from certification requirements. We performed a cost-effectiveness analysis (CEA) using two colon cancer populations (N = 1909) treated in different levels of certified hospitals (CHs) vs noncertified hospitals (NCHs) from a healthcare system's perspective. We matched patient-level data of incident colon cancer cases, diagnosed between 2008 and 2013 from a large statutory health insurance in Saxony, Germany, to calculate net treatment costs by phase (initial, continuing and terminal phase). The costs were supplemented with extra costs from 31 additional services required for certification. Effectiveness measure was total survival time in life-years. Outcome of interest was incremental costs per additional life-year. The annualized net colon cancer treatment costs by phase showed a U shape with high costs in the initial (mean €26 855; 95% CI €25 058-€28 652) and the terminal phases (mean €30 096; 95% CI €26 199-€33 993). The base-case CEA results and all sensitivity analyses consistently demonstrated longer survival and lower costs for the colon cancer cohort treated in CHs vs NCHs. To conclude, we used administrative data to derive the first cost-effectiveness evidence supporting that colon cancer care delivered in the certified cancer centers in Germany improves survival outcomes and saves costs from a healthcare system's perspective. Generalization of the study results should be exercised with caution.
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Orphan Medicine Incentives:
How to address the unmet needs of disease patients by transforming the European OMP landscape?
Copenhagen Economics (May 2021), Booklet.
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Income loss after a cancer diagnosis in Germany: An analysis based on the socio-economic panel survey.
Cancer Medicine (2021), 10(11): 3726–3740.
Cancer treatments often require intensive use of healthcare services and limit patients' ability to work, potentially causing them to become financially vulnerable. The present study is the first attempt to measure, on the German national level, the magnitude of absolute income loss after a cancer diagnosis.
This study analyzes data from the Socio-Economic Panel (SOEP) survey, one of the largest and most comprehensive household surveys in Germany, consisting of approximately 20,000 individuals, who are traced annually. The empirical strategy consists of ordinary least squares (OLS) and multinomial logistic estimators to measure changes in job income, work status, working hours, and pension as a result of reporting a cancer diagnosis for the period between 2009 and 2015. Sample consistency checks were conducted to limit measurement error biases.
Our results show that job incomes dropped between 26% and 28% within the year a cancer diagnosis was reported. The effect persisted for two years after the diagnosis and was no longer observable after four years. The finding was linked to an increased likelihood of unemployment and a reduction of working hours by 24%. Pension levels, on the other hand, were not affected by a cancer diagnosis.
These findings suggest that many cancer patients are exposed to financial hardship in Germany, particularly when the cancer diagnosis occurs during their working age and before requirements to obtain a pension are met. Further research seems warranted to identify particularly vulnerable patient groups.
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Cost-effectiveness of risk-based breast cancer screening: A systematic review.
International Journal of Cancer (2021). DOI: 10.1002/ijc.33593 (Epub ahead of print).
To analyse published evidence on the economic evaluation of risk-based screening (RBS), a full systematic literature review was conducted. After a quality appraisal, we compared the cost-effectiveness of risk-based strategies (low-risk, medium-risk and high-risk) with no screening and age-based screening. Studies were also analysed for modelling, risk stratification methods, input parameters, data sources and harms and benefits. The 10 modelling papers analysed were based on screening performance of film-based mammography (FBM) (three); digital mammography (DM) and FBM (two); DM alone (three); DM, ultrasound (US) and magnetic resonance imaging (one) and DM and US (one). Seven studies did not include the cost of risk-stratification, and one did not consider the cost of diagnosis. Disutility was incorporated in only six studies (one for screening and five for diagnosis). None of the studies reported disutility of risk-stratification (being considered as high-risk). Risk-stratification methods varied from only breast density (BD) to the combination of familial risk, genetic susceptibility, lifestyle, previous biopsies, Jewish ancestry and reproductive history. Less or no screening in low-risk women and more frequent mammography screening in high-risk women was more cost-effective compared to no screening and age-based screening. High-risk women screened annually yielded a higher mortality rate reduction and more quality-adjusted life years at the expense of higher cost and false positives. RBS can be cost effective compared to the alternatives. However, heterogeneity among risk-stratification methods, input parameters, and weaknesses in the methodologies hinder the derivation of robust conclusions. Therefore, further studies are warranted to assess newer technologies and innovative risk-stratification methods.
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PRO ("patient-reported outcomes") und Lebensqualität in der Onkologie.
[Patient-reported outcomes (PRO) and quality of life in oncology.]
Forum (2020), 35: 382-390.
[Article available on request]
It is widely accepted that with patient-centered care, attempting to meet the patient’s individual health needs and desired outcomes should be a primary objective of healthcare provision. In order to treat patients not only from a biological and clinical perspective but to also take into account the mental, psychosocial and financial dimensions of cancer and cancer care, the expectations and experience of patients need to be understood. This requires research into patient-reported outcomes (PRO), including but not limited to (self-reported) health-related quality of life (HRQoL). This article provides a brief overview of some of the recurring issues that arise when preference-based instruments are used to measure the HRQoL of cancer patients. Despite massive research efforts, substantial progress, and considerable interest, these instruments have not yet been used to their full potential. This observation is particularly striking in the context of approval of new cancer drugs. There is also a need for more research into PROs beyond HRQoL, which include the potentially far-reaching psychological, social, and financial consequences of cancer. It is therefore suggested to prioritize socioeconomic impact analyses from the perspective of patients and their relatives, including both caregivers and dependents (e.g. children), with a view towards generating robust evidence on the full dimension of the issue and towards identifying particularly vulnerable patient groups.
1. Comments on "Cost of decentralized CAR T-cell production in an academic nonprofit setting" by Schmitt M et al.
2. Reply to: Comments on "Cost of decentralized CAR T-cell production in an academic nonprofit setting" by Ran T et al.
International Journal of Cancer (2020).
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Cost of decentralized CAR T-cell production in an academic nonprofit setting.
International Journal of Cancer (2020), 147(12): 3438-3445.
Chimeric antigen receptor (CAR) T‐cell therapy is a promising immunotherapy with high acquisition costs, and it has raised concerns about affordability and sustainability in many countries. Furthermore, the current centralized production paradigm for the T cells is less than satisfactory. Therefore, several countries are exploring alternative T‐cell production modes. Our study is based on the T‐cell production experience in a nonprofit setting in Germany. We first identified the work steps and main activities in the production process. Then we determined the fixed costs and variable costs. Main cost components included personnel and technician salaries, expenditure on equipment, a clean room, as well as production materials. All costs were calculated in 2018 euros and converted into U.S. dollars. For a clean room with one machine for closed and automated manufacturing installed, annual fixed costs summed up to approximately €438 098 ($584 131). The variable cost per production was roughly €34 798 ($46 397). At the maximum capacity of one machine, total cost per product would be close to €60 000 ($78 849). As shown in the scenario analysis, if three machines were to be installed in the clean room, per production cost could be as low as €45 000 (roughly $59905). If a cheaper alternative to lentivirus was used, per production total cost could be further reduced to approximately €33 000 (roughly $44309). Decentralized T‐cell production might be a less costly and more efficient alternative to the current centralized production mode that requires a high acquisition cost.
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Allen Patienten gerecht werden - Gedanken eines Gesundheitsökonomen zur Covid-19-Krise.
Newspaper Article / Frankfurter Allgemeine Zeitung / No. 124, p. 20 (2020/05/29).
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HTA agencies need evidence-informed deliberative processes:
Comment on “Use of evidence-informed deliberative processes by health technology assessment agencies around the globe".
Int J Health Policy Manag (2020). DOI: 10.34172/ijhpm.2020.22 (Epub ahead of print).
There are at least two reasons why health technology assessment (HTA) agencies need to seek process-based solutions to support the legitimacy of healthcare resource allocation, ie, (i) in pluralistic societies, the existence of often conflicting and incommensurable claims (ie, the “fragmentation of value”) and the lack of a broadly accepted, ethically defensible analytical framework, and (ii) the well-documented loopholes of the conventional logic of cost-effectiveness (CE) with its reductionist concept of allocative efficiency, which fails to reflect the distributive dimension of resource allocation decisions in collectively financed health schemes.
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network.
Orphanet Journal of Rare Diseases, (2020) Jan 6; 15(1): 3.
The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre.
Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients’ clinical status, characteristic, and personal choice.
Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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