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.

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.

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.

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.

Cost-effectiveness of risk-based breast cancer screening: A systematic review.

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.

Do certified cancer centers provide more cost-effective care? A health economic analysis of colon cancer care in Germany using administrative data.

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.

Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests. METHODS: Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States. RESULTS: Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening. CONCLUSIONS: Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.

Resource allocation in the Covid-19 health crisis: are Covid-19 preventive measures consistent with the Rule of Rescue?

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.

Cost of decentralized CAR T-cell production in an academic nonprofit setting.

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.

Cost-Effectiveness of Colorectal Cancer Screening Strategies-A Systematic Review.

BACKGROUND & AIMS: Widespread screening for colorectal cancer (CRC) has reduced its incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide up-to-date evidence of the cost effectiveness of CRC screening strategies by answering 3 research questions. METHODS: We searched PubMed, National Institute for Health Research Economic Evaluation Database, Social Sciences Citation Index (via the Web of Science), EconLit (American Economic Association) and 3 supplemental databases for original articles published in English from January 2010 through December 2017. All monetary values were converted to US dollars (year 2016). For all research questions, we extracted, or calculated (if necessary), per-person costs and life years (LYs) and/or quality-adjusted LYs, as well as the incremental costs per LY gained or quality-adjusted LY gained compared with the baseline strategy. A cost-saving strategy was defined as one that was less costly and equally or more effective than the baseline strategy. The net monetary benefit approach was used to answer research question 2. RESULTS: Our review comprised 33 studies (17 from Europe, 11 from North America, 4 from Asia, and 1 from Australia). Annual and biennial guaiac-based fecal occult blood tests, annual and biennial fecal immunochemical tests, colonoscopy every 10 years, and flexible sigmoidoscopy every 5 years were cost effective (even cost saving in most US models) compared to no screening. In addition, colonoscopy every 10 years was less costly and/or more effective than other common strategies in the United States. Newer strategies such as computed tomographic colonography, every 5 or 10 years, was cost effective compared with no screening. CONCLUSIONS: In an updated review, we found that common CRC screening strategies and computed tomographic colonography continued to be cost effective compared to no screening. There were discrepancies among studies from different regions, which could be associated with the model types or model assumptions.

The cost incurred by victims of bullying from a societal perspective: estimates based on a German online survey of adolescents.

Being a victim of bullying is linked to various social, emotional and behavioral problems potentially leading to a reduced quality of life. Furthermore, victims of bullying may cause extensive costs for society, for example by an above-average need for healthcare services. The present study was designed to quantify the costs and the loss of quality of life attributable to bullying by comparing victims with a control group of non-bullied students. A cross-sectional sample of 1293 adolescents (mean age 14.07, SD = 1.36) and their parents reported on bullying victimization, quality of life (adolescents' self-report), and annual direct (medical and non-medical) as well as indirect costs (parents' self-report) from a societal perspective (all expressed in €, year 2014 and 2015). For frequent (20.6% of our sample; costs: €8461.80 p.a.) but not occasional (13.3%; costs: €2850.06) bullying, victimization was associated with significantly higher costs compared to non-bullied adolescents (costs: €3138.00; annual difference between frequently bullied students and controls: €5323.01 p.a.; p = 0.008). Cost drivers included increased direct medical costs, but mostly indirect costs caused by productivity losses of the parents. Self-reported quality of life of frequent victims was considerably reduced (T = - 10.96; p < 0.001); also occasional bullying showed significantly reduced values in global quality of life (T = - 5.73; p < 0.001). The present findings demonstrate that frequent bullying is associated with substantial cost to society and reduced quality of life of victims. This observation underscores the need for effective school-based bullying prevention and suggests a high potential of effective programs to be cost effective as well.

Budgetary Impact and Cost Drivers of Drugs for Rare and Ultrarare Diseases.

OBJECTIVES: To review recent studies reporting health care expenditures (budgetary impact) for orphan medicinal products (OMPs) in Europe and to contribute to our understanding of the cost drivers of nononcological OMPs by means of an empirical analysis in Germany. METHODS: A systematic search for relevant studies on rare diseases was conducted in PubMed and Embase (until December 2016). In addition, annual treatment costs of nononcological OMPs in Germany were analyzed with respect to five explanatory variables: total prevalence of disease, prevalence with added benefit, availability of alternative treatments for the same indication, extent/probability of treatment benefit, and evidence for a treatment effect on mortality. RESULTS: A total of nine studies with specific estimates of the budget impact of OMPs for a total of 11 countries were identified; one study addressed specifically ultrarare diseases. Annual per-capita spending for OMPs ranges from €1.32 in Latvia to €16 in France. Per-patient annual treatment costs vary between €27,811 and €1,647,627 in Germany. On the basis of the German data set, the regression analysis shows that log prevalence has a significant inverse relationship with log annual treatment cost. In this model, doubling the prevalence leads to a 43% decrease in annual treatment cost. CONCLUSIONS: Despite per-patient annual treatment costs ranging up to several hundreds of thousands of euros for some OMPs, per-capita spending for OMPs is relatively small. In this study an inverse relationship between prevalence and annual treatment costs was found.

[The health economics of cancer screening in Germany: Which population-based interventions are cost-effective?] / Gesundheitsökonomie der Krebsfrüherkennung in Deutschland: Welche Interventionen sind kosteneffektiv bei bevölkerungsweiter Umsetzung?

Only a small proportion of German health expenditure is spent on prevention and early detection (screening). The rationale for screening is to identify persons with disease precursors or at the early stage of diseases when they are still asymptomatic, in order to decrease disease-specific morbidity and mortality. In Germany, the economic evidence is one of the evaluation criteria for screening measures, which, among other things, takes into account the additional cost per additional case detected or per case-related event avoided, as well as a cost-benefit balance.For this purpose, cost-effectiveness analyses, which report marginal or incremental cost effectiveness ratios, comparing a measure with its appropriate alternatives, may be a useful tool. Their application requires a defensible benchmark (threshold) for cost effectiveness and a supplementary analysis of the necessary infrastructure and the budgetary impact associated with program implementation. Also (albeit not only) because of the usually long time required to observe the clinical outcomes of a screening measure, the economic evaluation of such programs regularly involves the application of decision analytic simulation models. With regard to cancer screening programs, the available models indicate an excellent cost-benefit ratio for the fecal occult blood test and colonoscopy for colorectal cancer screening and, similarly, for the use of mammography for breast cancer screening. On the other hand, the economic evidence in favor of low-dose computed tomography for lung cancer screening does not yet appear sufficiently strong, and the currently available health economic evidence does not support the use of PSA testing for prostate screening.

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.

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.

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.

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.

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.