Optimal timing of a colonoscopy screening schedule depends on adenoma detection, adenoma risk, adherence to screening and the screening objective: A microsimulation study.

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost reduction) and the setting in which screening is performed. We used our established open-source microsimulation model CMOST to calculate optimized colonoscopy schedules with one, two, three or four screening colonoscopies between 20 and 90 years of age. A single screening colonoscopy was most effective in reducing life years lost from CRC when performed at 55 years of age. Two, three and four screening colonoscopy schedules saved a maximum number of life years when performed between 49-64 years; 44-69 years; and 40-72 years; respectively. However, for maximum incidence and mortality reduction, screening colonoscopies needed to be scheduled 4-8 years later in life. The optimum was also influenced by adenoma detection efficiency with lower values for these parameters favoring a later starting age of screening. Low adherence to screening consistently favored a later start and an earlier end of screening. In a personalized approach, optimal screening would start earlier for high-risk patients and later for low-risk individuals. In conclusion, our microsimulation-based approach supports colonoscopy screening schedule between 45 and 75 years of age but the precise timing depends on the objective of screening, as well as assumptions regarding individual CRC risk, efficiency of adenoma detection during colonoscopy and adherence to screening.

Quality Appraisal in Systematic Literature Reviews of Studies Eliciting Health State Utility Values: Conceptual Considerations.

BACKGROUND: The increasing number of studies that generate health state utility values (HSUVs) and the impact of HSUVs on cost-utility analyses make a robust tailored quality appraisal (QA) tool for systematic reviews of these studies necessary. OBJECTIVE: This study aimed to address conceptual issues regarding QA in systematic reviews of studies eliciting HSUVs by establishing a consensus on the definitions, dimensions and scope of a QA tool specific to this context. METHODS: A modified Delphi method was used in this study. An international multidisciplinary panel of seven experts was purposively assembled. The experts engaged in two anonymous online survey rounds. After each round, the experts received structured and controlled feedback on the previous phase. Controlled feedback allowed the experts to re-evaluate and adjust their positions based on collective insights. Following these surveys, a virtual face-to-face meeting was held to resolve outstanding issues. Consensus was defined a priori at all stages of the modified Delphi process. RESULTS: The response rates to the first-round and second-round questionnaires and the virtual consensus meeting were 100%, 86% and 71%, respectively. The entire process culminated in a consensus on the definitions of scientific quality, QA, the three QA dimensions-reporting, relevance and  methodological quality-and the scope of a QA tool specific to studies that elicit HSUVs. CONCLUSIONS: Achieving this consensus marks a pivotal step towards developing a QA tool specific to systematic reviews of studies eliciting HSUVs. Future research will build on this foundation, identify QA items, signalling questions and response options, and develop a QA tool specific to studies eliciting HSUVs.

The socioeconomic impact of cancer on patients and their relatives: Organisation of European Cancer Institutes task force consensus recommendations on conceptual framework, taxonomy, and research directions.

Loss of income and out-of-pocket expenditures are important causes of financial hardship in many patients with cancer, even in high-income countries. The far-reaching consequences extend beyond the patients themselves to their relatives, including caregivers and dependents. European research to date has been limited and is hampered by the absence of a coherent theoretical framework and by heterogeneous methods and terminology. To address these shortages, a task force initiated by the Organisation of European Cancer Institutes (OECI) produced 25 recommendations, including a comprehensive definition of socioeconomic impact from the perspective of patients and their relatives, a conceptual framework, and a consistent taxonomy linked to the framework. The OECI task force consensus statement highlights directions for future research with a view towards policy relevance. Beyond descriptive studies into the dimension of the problem, individual severity and predictors of vulnerability should be explored. It is anticipated that the consensus recommendations will facilitate and enhance future research efforts into the socioeconomic impact of cancer and cancer care, providing a crucial reference point for the development and validation of patient-reported outcome instruments aimed at measuring its broader effects.

Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.

Background: Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany. Method: DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro. Result: Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses. Conclusion: The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.

Measurement invariance and adapted preferences: evidence for the ICECAP-A and WeRFree instruments.

BACKGROUND: Self-report instruments are used to evaluate the effect of interventions. However, individuals adapt to adversity. This could result in individuals reporting higher levels of well-being than one would expect. It is possible to test for the influence of adapted preferences on instrument responses using measurement invariance testing. This study conducts such a test with the Wellbeing Related option-Freedom (WeRFree) and ICECAP-A instruments. METHODS: A multi-group confirmatory factor analysis was conducted to iteratively test four increasingly stringent types of measurement invariance: (1) configural invariance, (2) metric invariance, (3) scalar invariance, and (4) residual invariance. Data from the Multi Instrument Comparison study were divided into subsamples that reflect groups of participants that differ by age, gender, education, or health condition. Measurement invariance was assessed with (changes in) the Comparative Fit Index (CFI), Root Mean Square Error of Approximation (RMSEA), and Root Mean Square Residual (SRMR) fit indices. RESULTS: For the WeRFree instrument, full measurement invariance could be established in the gender and education subsamples. Scalar invariance, but not residual invariance, was established in the health condition and age group subsamples. For the ICECAP-A, full measurement invariance could be established in the gender, education, and age group subsamples. Scalar invariance could be established in the health group subsample. CONCLUSIONS: This study tests the measurement invariance properties of the WeRFree and ICECAP-A instruments. The results indicate that these instruments were scalar invariant in all subsamples, which means that group means can be compared across different subpopulations. We suggest that measurement invariance of capability instruments should routinely be tested with a reference group that does not experience a disadvantage to study whether responses could be affected by adapted preferences.

Developing a Conceptual Framework for Socioeconomic Impact Research in European Cancer Patients: A 'Best-Fit' Framework Synthesis.

BACKGROUND: Multiple studies have indicated a socioeconomic impact of cancer and cancer care on patients and their families. Existing instruments designed to measure this impact lack consensus in their conceptualization of the issue. Further, various terminologies have been used in the literature (e.g., financial burden, financial hardship, financial stress) without clear definitions and consistent conceptual background. Based on a targeted review of existing models addressing the socioeconomic impact of cancer, our goal was to develop a comprehensive framework from a European perspective. METHOD: A 'best-fit' framework synthesis was applied. First, we systematically identified existing models to generate a priori concepts. Second, we systematically identified relevant European qualitative studies and coded their results against these a priori concepts. Inclusion and exclusion criteria were predefined and applied thoroughly in these processes. Thematic analysis and team discussions were applied to finalize the (sub)themes in our proposed conceptual framework. Third, we examined model structures and quotes from qualitative studies to explore relationships among (sub)themes. This process was repeated until no further change in (sub)themes and their relationships emerged. RESULT: Eighteen studies containing conceptual models and seven qualitative studies were identified. Eight concepts and 20 sub-concepts were derived from the included models. After coding the included qualitative studies against the a priori concepts and following discussions among team members, seven themes and 15 sub-themes were included in our proposed conceptual framework. Based on the identified relationships, we categorized themes into four groups: causes, intermediate consequences, outcomes and risk factors. CONCLUSION: We propose a Socioeconomic Impact Framework based on a targeted review and synthesis of existing models in the field and adapted to the European perspective. Our work contributes as an input to a European consensus project on socioeconomic impact research by an Organization European Cancer Institute (OECI) Task Force.

Health Technology Assessment-Informed Decision Making by the Federal Joint Committee/Institute for Quality and Efficiency in Health Care in Germany and the National Institute for Health and Care Excellence in England: The Role of Budget Impact.

OBJECTIVES: This study aimed 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 (Gemeinsamer Bundesausschuss [GBA]) and the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [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 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 outcomes 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 single technology appraisals (inverted-U relationship, P < .1) and IQWiG recommendations (increasing linear relationship, P < .05), but not with GBA decisions (P > .1). Nevertheless, given that 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.

Modeling the Natural History and Screening Effects of Colorectal Cancer Using Both Adenoma and Serrated Neoplasia Pathways: The Development, Calibration, and Validation of a Discrete Event Simulation Model.

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. Highlights: This article presents a new discrete event simulation model, DECAS, which models both adenoma-carcinoma and serrated neoplasia pathways for colorectal cancer (CRC) development and CRC screening effects.DECAS is calibrated based on a Bayesian inference method using the data from German screening colonoscopy program, which consists of more than 5 million first-time average-risk participants aged 55 years and older in 2003 to 2014.DECAS is flexible for evaluating various CRC screening strategies and can differentiate screening effects in different parts of the colon.DECAS is validated with large screening sigmoidoscopy and colonoscopy clinical study data and can be further used to evaluate the (cost-)effectiveness of German colorectal cancer screening strategies.

Economic Burden of Pancreatic Cancer in Europe: a Literature Review.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Out-of-pocket payments and loss of income among long-term breast cancer survivors in Germany: a multi-regional population-based study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: For some survivors in Germany, financial burden can be considerably high despite comprehensive healthcare and support from social security. IMPLICATIONS FOR CANCER SURVIVORS: OOP payments related to domestic help and nursing staff as well as to outpatient care are most frequent.

Quality appraisal for systematic literature reviews of health state utility values: a descriptive analysis.

BACKGROUND: Health state utility values (HSUVs) are an essential input parameter to cost-utility analysis (CUA). Systematic literature reviews (SLRs) provide summarized information for selecting utility values from an increasing number of primary studies eliciting HSUVs. Quality appraisal (QA) of such SLRs 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 published SRLs of studies eliciting HSUVs and generate a list of commonly used items. METHODS: A comprehensive literature search was conducted in PubMed and Embase from 01.01.2015 to 15.05.2021. SLRs of empirical studies eliciting HSUVs that were published in English were included. We extracted descriptive data, which included QA tools checklists or good practice recommendations used or cited, items used, and the methods of incorporating QA results into study findings. Descriptive statistics (frequencies of use and occurrences of items, acceptance and counterfactual acceptance rates) were computed and a comprehensive list of QA items was generated. RESULTS: A total of 73 SLRs were included, comprising 93 items and 35 QA tools and good recommendation practices. The prevalence of QA was 55% (40/73). Recommendations by NICE and ISPOR guidelines appeared in 42% (16/40) of the SLRs that appraised quality. The most commonly used QA items in SLRs were response rates (27/40), statistical analysis (22/40), sample size (21/40) and loss of follow up (21/40). Yet, the most commonly featured items in QA tools and GPRs were statistical analysis (23/35), confounding or baseline equivalency (20/35), and blinding (14/35). Only 5% of the SLRS used QA to inform the data analysis, with acceptance rates of 100% (in two studies) 67%, 53% and 33%. The mean counterfactual acceptance rate was 55% (median 53% and IQR 56%). CONCLUSIONS: There is a considerably low prevalence of QA in the SLRs of HSUVs. Also, there is a wide 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.

Use of the incremental cost-effectiveness ratio for decision-making policies-what is the problem? A perspective paper.

INTRODUCTION: 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 manner. AREAS COVERED: We reprise some of the key inadequacies of QALY-based ICER analyses and suggest that there are other means including multicriteria decision analysis (MCDA) and cost-benefit analysis based on willingness to pay (WTP) measures by which to partially mitigate these weaknesses. EXPERT OPINION: 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.

Survival and comorbidities in lung cancer patients: Evidence from administrative claims data in Germany.

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.

Health and life insurance-related problems in very long-term cancer survivors in Germany: a population-based study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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].

BACKGROUND: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Estimation of the stage-wise costs of breast cancer in Germany using a modeling approach.

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.

Health technology assessment (HTA) in England, France and Germany: what do matched drug pairs tell us about recommendations by national HTA agencies?

Aims: 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). Methods: 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. Results: 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. Conclusion: The findings indicate substantial variations in HTAs, although cancer-related outcomes seem to diverge less than non-cancer results.

How Much Does It Cost to Research and Develop a New Drug? A Systematic Review and Assessment.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.