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Background: Recent studies have underscored the potential of innovative administration methods to mitigate the capacity burden on healthcare systems, without compromising the quality of care. This study assessed and compared the resource utilization and associated costs of two distinct administration modes of immune checkpoint inhibitors: the innovative elastomeric pump and conventional intravenous infusion. This comparison can inform sustainable healthcare practices and healthcare decision-making to optimize treatment efficiency in an era of escalating healthcare demands. Methods: In this micro-costing study, data on resource use and time allocation for drug preparation and administration were collected using an observational, non-interventional study design. Data were registered at the oncology daycare unit and hospital pharmacy. Cost categories included drug acquisition, disposable materials, healthcare professional time for drug administration, drug preparation, and patient time spent at the oncology day care unit. Results: Drug administration through the elastomeric pump resulted in substantially lower healthcare costs when compared to conventional infusion, particularly due to reduced labor and chair time. The elastomeric pump reduced the total chair time by 78% and nurse time by 55%. Total average costs (excluding drug costs) were €103,47 and €77.99 for conventional infusion and the elastomeric pump, respectively, showcasing potential savings of €25.48 (P < 0.001) per administration. Conclusions: This study demonstrated that the elastomeric pump not only offers substantial cost savings but also enhances the treatment capacity of the oncology day care unit. These findings support the adoption of the elastomeric pump in clinical settings as a cost-saving and efficient alternative to conventional infusion. Trial registration: This study has been registered in the National Trial Register (NTR), with the reference number NTR NL9473. Registration date: 05-05-2021. [ABSTRACT FROM AUTHOR]

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised. Results: A total of 57 experts from 15 countries responded to the survey. The WGs were attended by (i) 11, (ii) 10, (iii) 12, and (iv) 12 experts, respectively, representing a variety of national backgrounds and stakeholder profiles. The most relevant action points identified were as follows: (i) incorporation of clinical context into population, intervention, comparator, outcomes (PICO) schemes, (ii) timely provision of up-to-date therapeutic guidelines, (iii) ensuring the inclusion of MCBS insights into the EU HTA process, and (iv) considering randomized controlled trials (RCTs) as the gold standard and leveraging regulatory insights if development programs only include single-arm trials. Conclusions: The involvement of medical societies is a critical success factor for the EU HTA. The identified key action points foster the involvement of patient associations and medical societies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective. Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening. • This is the first study with a paired US-MRI design. • This design will allow a head-to-head comparison in both diagnostics and patient-acceptance. • We expect that SMS can contribute to a higher survival rate. [ABSTRACT FROM AUTHOR]

Background: Hip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries. Methods: We performed a retrospective serial cross‐sectional cohort study of adults aged ≥66 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population‐representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30‐day readmission rates, and time‐to‐surgery. Results: The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30‐day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%–45%) and THA (0.2%–10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%–60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30‐day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada). Conclusions: We observed substantial between‐country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence‐based surgical approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: CAPRI-3 is an observational registry on metastatic prostate cancer that uses artificial intelligence (AI) for patient identification and data collection. The aim of this study is to demonstrate the reliability and efficiency of this method. Our deliberate effort to maximize the negative predictive value of our patient-identification algorithm to rule out unsuitable candidates without manual screening was successful and reached 94.8%. Completeness and accuracy of data extraction were 92.3% or higher but were lower (up to 10%) for date fields and inaccessible data (images/pdf). The AI-driven approach, including additional manual quality control, was much faster than full manual data collection (105 vs. 300 min per patient). In conclusion, the AI-driven approach of the CAPRI-3 registry is largely reliable and timesaving but manual quality control is needed for the less reliable and inaccessible data. Background: Manual data collection is still the gold standard for disease-specific patient registries. However, CAPRI-3 uses text mining (an artificial intelligence (AI) technology) for patient identification and data collection. The aim of this study is to demonstrate the reliability and efficiency of this AI-driven approach. Methods: CAPRI-3 is an observational retrospective multicenter cohort registry on metastatic prostate cancer. We tested the patient-identification algorithm and automated data extraction through manual validation of the same patients in two pilots in 2019 and 2022. Results: Pilot one identified 2030 patients and pilot two 9464 patients. The negative predictive value of the algorithm was maximized to prevent false exclusions and reached 94.8%. The completeness and accuracy of the automated data extraction were 92.3% or higher, except for date fields and inaccessible data (images/pdf) (10–88.9%). Additional manual quality control took over 3 h less time per patient than the original fully manual CAPRI registry (105 vs. 300 min). Conclusions: The CAPRI-3 patient-identification algorithm is a sound replacement for excluding ineligible candidates. The AI-driven data extraction is largely accurate and complete, but manual quality control is needed for less reliable and inaccessible data. Overall, the AI-driven approach of the CAPRI-3 registry is reliable and timesaving. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding health‐related quality of life (HRQoL) in patients with steroid‐refractory acute graft‐versus‐host disease (SR‐aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ‐5D‐5L, EORTC QLQ‐C30, and FACT‐BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). Methods: Descriptive statistics were used to describe baseline patient and disease characteristics, EQ‐5D dimension scores and values, EQ VAS scores, EORTC QLQ‐C30 scale/item and summary scores, and FACT‐BMT subscale and total scores. Results: The mean EQ‐5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self‐care, and 72% with anxiety/depression. The mean EORTC QLQ‐C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT‐BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well‐being to 23.94 for social/family well‐being. Conclusion: Our study showed that HRQoL in patients with SR‐aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority. [ABSTRACT FROM AUTHOR]

Background: The phase 3 clinical trial KEYNOTE-426 suggested a higher efficacy regarding overall survival (OS) and progression-free survival (PFS) of pembrolizumab+axitinib compared to sunitinib as a first-line treatment for patients with advanced renal cell carcinoma. In this analysis, the potential cost-effectiveness of this combination treatment versus sunitinib for patients with advanced clear-cell renal cell carcinoma (accRCC) was examined from the societal perspective in the Netherlands. Methods: For this analysis, a partitioned survival model was constructed. Clinical data were obtained from the published KEYNOTE-426 trial reports; data on costs and (dis-)utilities were derived from published literature. Costs outside of the healthcare sector included treatment-related travel, informal care and productivity loss. Next to a probabilistic scenario analysis, various scenario analyses were performed that aimed at survival extrapolation, different utility values, treatment duration and drug pricing, as well as restricting the cohort to patients with an intermediate or poor prognosis. Further, a budget impact analysis over three years was conducted, in which a sensitivity analysis concerning ranges in costs and the number of patients was applied. Moreover, a scenario concerning increasing market penetration of pembrolizumab+axitinib up to a market share of 80% in the third year was analyzed. Results: The incremental cost-effectiveness ratio (ICER) of pembrolizumab +axitinib was estimated at €368,396/quality-adjusted life year (QALY) gained, with an incremental QALY gain of 0.55 over sunitinib. The probability of costeffectiveness at a willingness-to-pay threshold of €80,000/QALY was estimated at 0%, a 50% probability was estimated at €340,000/QALY. Cost-effectiveness was not achieved in any of the applied scenarios. The budget impact over three years amounted to €417.3 million upon instantaneous and full replacement of sunitinib, and to €214.9 million with increasing market penetration. Conclusion: Pembrolizumab+axitinib was not estimated to be cost-effective compared to sunitinib as a first-line treatment for patients with accRCC in the Netherlands from a societal perspective. In none of the analyzed scenarios, costeffectiveness was achieved. However, price reductions and shorter treatment durations might lead to a more favorable ICER. [ABSTRACT FROM AUTHOR]

Background: Although expanded access is an increasingly used pathway for patients to access investigational medicine, little is known on the magnitude and content of published scientific research collected via expanded access. Methods: We performed a review of all peer-reviewed expanded access publications between January 1, 2000 and January 1, 2022. We analyzed the publications for drugs, diseases, disease area, patient numbers, time, geographical location, subject, and research methodology (single center/multicenter, international/national, prospective/retrospective). We additionally analyzed endpoints reported in all COVID-19-related expanded access publications. Results: We screened 3810 articles and included 1231, describing 523 drugs for 354 diseases for 507,481 patients. The number of publications significantly increased over time ( p < 0.001 ). Large geographical disparities existed as Europe and the Americas accounted for 87.4% of all publications, whereas Africa only accounted for 0.6%. Oncology and hematology accounted for 53% of all publications. Twenty-nine percent of all expanded access patients (N = 197,187) reported on in 2020 and 2021 were treated in the context of COVID-19. Conclusions: By summarizing characteristics of patients, diseases, and research methods described in all scientific literature published on expanded access, we provide a unique dataset for future research. We show that published scientific research on expanded access has surged over the past decades, partly due to COVID-19. However, international collaboration and equity in geographic access remain an issue of concern. Lastly, we stress the need for harmonization of research legislation and guidance on the value of expanded access data within real-world data frameworks to improve equity in patient access and streamline future expanded access research. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) based algorithms for classification of suspicious skin lesions have been implemented in mobile phone apps (mHealth), but their effect on healthcare systems is undocumented. In 2019, a large Dutch health insurance company offered 2.2 million adults free access to an mHealth app for skin cancer detection. To study the impact on dermatological healthcare consumption, we conducted a retrospective population-based pragmatic study. We matched 18,960 mHealth-users who completed at least one successful assessment with the app to 56,880 controls who did not use the app and calculated odds ratios (OR) to compare dermatological claims between both groups in the first year after granting free access. A short-term cost-effectiveness analysis was performed to determine the cost per additional detected (pre)malignancy. Here we report that mHealth-users had more claims for (pre)malignant skin lesions than controls (6.0% vs 4.6%, OR 1.3 (95% CI 1.2–1.4)) and also a more than threefold higher risk of claims for benign skin tumors and nevi (5.9% vs 1.7%, OR 3.7 (95% CI 3.4–4.1)). The costs of detecting one additional (pre)malignant skin lesion with the app compared to the current standard of care were €2567. Based on these results, AI in mHealth appears to have a positive impact on detecting more cutaneous (pre)malignancies, but this should be balanced against the for now stronger increase in care consumption for benign skin tumors and nevi. [ABSTRACT FROM AUTHOR]

Key Points: Question: How do treatment patterns and outcomes for older patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Findings: In this study of 289 376 patients aged 66 years or older hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI across 6 health systems, adjusted 30-day and 1-year mortality rates were higher for low-income patients, whereas rates of cardiac catheterization and percutaneous coronary interventions were lower. High-income patients also had shorter length of stay and lower rates of readmissions. Meaning: These results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems. Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, −2.8 percentage points [95% CI, −4.1 to −1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, −9.1 percentage points [95% CI, −16.7 to –1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems. This serial cross-sectional cohort study compares whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. [ABSTRACT FROM AUTHOR]

Immunotherapy offers a distinctive mechanism of action compared to traditional treatments, arising from additional value dimensions that may not be captured in standard health technology assessments. Cancer patients may have the expectation that immunotherapy provides durable, long-term survival gains. Moreover, some patients may be willing to take a 'risk' to undergo immunotherapy to achieve better survival outcomes. We reviewed quantitative methods that explored patients' risk preferences in their non-small cell lung cancer (NSCLC) treatment choices, in PubMed (MEDLINE), from January 1, 2015, until July 1, 2022. The consideration of a value dimension ('hope') based on patients' risk-seeking preferences is specifically addressed for the valuation of immune checkpoint inhibitors in NSCLC. We reported that the quantitative methods that aim to measure patients' risk preferences or 'hope' empirically are emerging. Value assessments should not only comprise survival improvements for the mean or median patient but also consider methods that reflect durable, long-term overall survival gains for risk-seeking patients. However, the published evidence for incorporating 'hope' based on patients' stated preferences for uncertain treatment profiles is not strong, and future research could strengthen this evidence base. We encourage further research on the development and validation of quantification methods to incorporate 'hope' and risk preferences of patients treated with immunotherapy for NSCLC and beyond. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy delivers more precise treatment compared with conventional radiotherapy. While this innovation entails investment costs, the information about the treatment costs per patient is limited. This information gap might prevent policymakers from making informed decisions. This study aims to calculate the costs of Proton therapy at a single center during the start-up phase and to provide essential information for the health technology assessment of proton therapy. The total cost of proton therapy varied between EUR 12,062 for eye melanoma and EUR 89,716 for head and neck cancer. Overall, indirect costs were the most significant cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Nevertheless, to have an estimation that reflects the matured cost of proton therapy which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. However, this study provided insights into the financial situation of a new proton therapy center during its ramp-up period and laid the first stone for future costing studies. Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. Methods: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. Results: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Conclusion: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the cost-effectiveness, budget impact (BI), and impact of uncertainty of future developments concerning whole-genome sequencing (WGS) as a clinical diagnostic test compared with standard of care (SoC) in patients with locally advanced and metastatic non–small cell lung cancer. A total of 3 likely scenarios to take place within 5 years (according to experts) were simulated using a previously developed, peer reviewed, and published decision model. The scenarios concerned "WGS results used for treatment selection" (scenario 1), "WGS-based biomarker for immunotherapy" (scenario 2), and "off-label drug approval for WGS results" (scenario 3). Two diagnostic strategies of the original model, "SoC" and "WGS as a diagnostic test" (base model), were used to compare our scenarios with. Outcomes were reported for the base model, all scenarios separately, combined (combined unweighted), and weighted by likelihood (combined weighted). Cost-effectiveness, BI, and value of information analyses were performed for WGS compared with SoC. Total costs and quality-adjusted life-years for SoC in metastatic non–small cell lung cancer were €149 698 and 1.235. Incremental outcomes of WGS were €1529/0.002(base model), −€222/0.020(scenario 1), −€2576/0.023(scenario 2), €388/0.024(scenario 3), −€5041/0.060(combined unweighted), and −€1715/0.029(combined weighted). The annual BI for adopting WGS for this population in The Netherlands ranged between €682 million (combined unweighted) and €714 million (base model). The consequences of uncertainty amounted to €3.4 million for all scenarios (combined weighted) and to €699 000 for the diagnostic yield of WGS alone (combined weighted). Our findings suggest that it is likely for WGS to become cost-effective within the near future if it identifies more patients with actionable targets and show the impact of uncertainty regarding its diagnostic yield. Modeling future scenarios can be useful to consider early adoption of WGS while timely anticipating on unforeseen developments before final conclusions are reached. • Modeling quantified scenarios using a probabilistic economic decision model can be useful to timely anticipate on unforeseen future developments relevant to the implementation of a new technology. A recent example of such technology is the use of whole-genome sequencing (WGS) as a diagnostic test compared with standard of care in patients with locally advanced and metastatic non–small cell lung cancer. • Scenarios about the use of WGS results for treatment selection, a WGS-based biomarker for immunotherapy, and off-label drug approval for WGS results were found cost-effective compared with standard of care, with the incremental net monetary benefits ranging from €1525 to €9815 (willingness to pay threshold: €80 000/quality-adjusted life-year). The annual budget impact for adopting WGS ranged between €682 million and €714 million. The consequences of uncertainty amounted to €699 000 for the diagnostic yield of WGS alone. • Current findings suggest that the field of clinical oncology could move into a direction where WGS will become cost-effective as a molecular diagnostic test in non–small cell lung cancer if it detects more patients with actionable targets and costs decrease. Policy makers and researchers should timely anticipate on this and consider the adoption of WGS as long as it is accompanied with further research focused on the diagnostic yield of WGS to reach final conclusions. [ABSTRACT FROM AUTHOR]

We conducted a systematic literature review to identify and review the concepts and questionnaires used to assess the impact of caregiving on caregivers for adults with a mental disorder. With our study, we aimed to provide an overview and categorize the conceptualization and operationalization of the impact of caregiving, with special attention for the complexity and multi-conceptualization of concepts. Embase, Medline, PsycInfo, Web of Science Core Collection, Cochrane Central Register of Trials, Cinahl Plus, Econlit and Google Scholar were systematically searched for articles from 1 January 2004 to 31 December 2019. Eligible articles were peer-reviewed studies that assessed the impact of caregiving for informal caregivers of adults with a reported mental disorder by means of a questionnaire. The complete study protocol can be found on PROSPERO (CRD42020157300). A total of 144 questionnaires were identified that assessed the impact of caregiving. Based on similarities in meaning, concepts were classified into 15 concept clusters. The most frequently assessed concept clusters were mental health, caregiving burden, other caregiving consequences, family impact, and overall health-related outcomes. The use of concept clusters differed per diagnosis group, with diagnoses, such as schizophrenia, using a wide range of caregiving impact concepts and other diagnoses, such as personality disorders, only using a limited range of concepts. This is the first study that identified and reviewed the concepts and questionnaires that are used to assess the impact of caregiving. Caregiving is researched from a broad array of perspectives, with the identification of a variety of concepts and dimensions and use of non-specific questionnaires. Despite increasing interest in this field of research, a high degree of variability remains abundant with limited consensus. This can partially be accredited to differences in the naming of concepts. Ultimately, this review can serve as a reference to researchers who wish to assess the impact of caregiving and require further insight into concepts and their respective questionnaires. [ABSTRACT FROM AUTHOR]

• This study proposes a conceptual framework for a broad health technology assessment (HTA) of medical artificial intelligence (AI). • A targeted literature search was conducted to distill relevant medical AI issues, and 25 issues were grouped into four focus areas: performance & Evidence, human & Organizational, legal & Ethical, and transparency & usability. • Using the proposed list of 25 issues in HTA requires an approach that is tailored to distinct types of medical AI. As current health technology assessment (HTA) frameworks do not provide specific guidance on the assessment of medical artificial intelligence (AI), this study aimed to propose a conceptual framework for a broad HTA of medical AI. A systematic literature review and a targeted search of policy documents was conducted to distill the relevant medical AI assessment elements. Three exemplary cases were selected to illustrate various elements: (1) An application supporting radiologists in stroke-care (2) A natural language processing application for clinical data abstraction (3) An ICU-discharge decision-making application. A total of 31 policy documents and 9 academic publications were selected, from which a list of 29 issues was distilled. The issues were grouped by four focus areas: (1) Technology & Performance, (2) Human & Organizational, (3) Legal & Ethical and (4) Transparency & Usability. Each assessment element was extensively discussed in the test, and the elements clinical effectiveness, clinical workflow, workforce, interoperability, fairness and explainability were further highlighted through the exemplary cases. The current methodology of HTA requires extension to make it suitable for a broad evaluation of medical AI technologies. The 29-item assessment list that we propose needs a tailored approach for distinct types of medical AI, since the conceptualisation of the issues differs across applications. [ABSTRACT FROM AUTHOR]

Patients with rare diseases often have limited or no options for approved treatments or participation in clinical trials. In such cases, expanded access (or "compassionate use") provides a potential means of accessing unapproved investigational medicines. It is also possible to capture and analyze clinical data from such use, but doing so is controversial. In this perspective, we offer examples of evidence derived from expanded access programs for rare diseases to illustrate its potential value to the decision-making of regulators and payers in the European Union and the United States. We discuss ethical and regulatory aspects to the use of expanded access data, with a focus on rare disease medicines. The heterogeneous approach to expanded access among countries within the European Union leaves uncertainties to what extent data can be collected and analyzed. We recommend the issuance of new guidance on data collection during expanded access, harmonization of European pathways, and an update of existing European compassionate use guidance. We hereby aim to clarify the supportive role of expanded access in evidence generation. Harmonization across Europe of expanded access regulations could reduce manufacturer burdens, improve patient access, and yield better data. These changes would better balance the need to generate quality evidence with the desire for pre-approval access to investigational medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients who receive radiotherapy often suffer from adverse effects that require healthcare resources to manage. This study summarized evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and provided recommendations for including this evidence in economic evaluations. Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was overestimated or underestimated. Background: Despite the need for a proper economic evaluation of new radiotherapies, the economic burden of radiotherapy-induced adverse effects remains unclear. A systematic review has been conducted to identify the existing evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and also to provide recommendations for including this evidence in economic evaluations. Methods: This systematic review of healthcare resource use and/or medical costs related to radiotherapy-induced adverse effects was performed up until 2020, focusing on patients with head and neck cancer, brain cancer, prostate cancer, eye cancer and breast cancer. Results: Resource use for treating the same adverse effects varied considerably across studies; for instance, the cost for mucositis ranged from USD 2949 to USD 17,244. This broad range could be related to differences in (1) severity of adverse effects in the study population, (2) study design, (3) cost estimation approach and (4) country and clinical practice. Conclusions: Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was being overestimated or underestimated in economic evaluation for radiotherapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Endoxifen is the active metabolite of tamoxifen, and a minimal plasma concentration of 16 nM has been suggested as a threshold above which it is effective in reducing the risk of breast cancer recurrence. The aim of the current analysis was to investigate the cost-effectiveness of therapeutic drug monitoring (TDM)-guided tamoxifen dosing. Methods: A cost-effectiveness analysis was performed from a Dutch healthcare perspective, using a partitioned survival model and a lifetime horizon. The reduction in subtherapeutic treatment following TDM is modelled as improved rates of recurrence-free survival (RFS) and overall survival (OS) in comparison to standard tamoxifen treatment. A probabilistic sensitivity analysis (PSA) and a series of scenario analyses were performed to assess the robustness of the results. Results: Base-case results estimated a total increase in life years and quality-adjusted life years (QALYs) for TDM of 0.40 and 0.53, respectively. Total costs for TDM and standard tamoxifen treatment are €32,893 and €39,524, respectively. The TDM intervention results in both more QALYs and less healthcare costs, indicating a dominating effect for TDM. The PSA results indicate that the probability of TDM being cost-effective is 92% when using a willingness-to-pay threshold of €20,000. Conclusions: TDM-guided dose optimization of tamoxifen is estimated to save costs and increase QALYs for early breast cancer patients. [ABSTRACT FROM AUTHOR]

Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of developing symptomatic skeletal events (SSEs). We retrospectively investigated incidence of SSEs and the use of bone health agents (BHA) in a contemporary, treated bone metastatic CRPC population. Although patients with early BHA use had lower incidence rates of SSE and longer SSE-free survival, there was an undertreatment with BHAs in our population. Especially in patients with risk factors as pain and/or opioid use and prior SSE, timely initiation of BHAs is recommended. Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. Patients and Methods: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. Results: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001). Conclusion: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE. [ABSTRACT FROM AUTHOR]

Background: Current first-line disease-modifying therapies (DMT) for multiple sclerosis (MS) patients are injectable or oral treatments. The Optogenerapy consortium is developing a novel bioelectronic cell-based implant for controlled release of beta-interferon (IFNβ1a) protein into the body. The current study estimated the potential cost effectiveness of the Optogenerapy implant (hereafter: Optoferon) compared with injectable IFNβ1a (Avonex). Methods: A Markov model simulating the costs and effects of Optoferon compared with injectable 30 mg IFNβ1a over a 9-year time horizon from a Dutch societal perspective. Costs were reported in 2019 Euros and discounted at a 4% annual rate; health effects were discounted at a 1.5% annual rate. The cohort consisted of 35-year-old, relapsing–remitting MS patients with mild disability. The device is implanted in a daycare setting, and is replaced every 3 years. In the base-case analysis, we assumed equal input parameters for Optoferon and Avonex regarding disability progression, health effects, adverse event probabilities, and acquisition costs. We assumed reduced annual relapse rates and withdrawal rates for Optoferon compared with Avonex. Sensitivity, scenario, value of information, and headroom analysis were performed. Results: Optoferon was the dominant strategy with cost reductions (− €26,966) and health gains (0.45 quality-adjusted life-years gained). A main driver of cost differences are the acquisition costs of Optoferon being 2.5 times less than the costs of Avonex. The incremental cost-effectiveness ratio was most sensitive to variations in the annual acquisition costs of Avonex, the annual withdrawal rate of Avonex and Optoferon, and the disability progression of Avonex. Conclusion: Innovative technology such as the Optoferon implant may be a cost-effective therapy for patients with MS. The novel implantable mode of therapeutic protein administration has the potential to become a new mode of treatment administration for MS patients and in other disease areas. However, trials are needed to establish safety and effectiveness. [ABSTRACT FROM AUTHOR]

Background: Advanced non-small-cell lung cancer (NSCLC) harbours many genetic aberrations that can be targeted with systemic treatments. Whole-genome sequencing (WGS) can simultaneously detect these (and possibly new) molecular targets. However, the exact added clinical value of WGS is unknown. Objective: The objective of this study was to determine the early cost effectiveness of using WGS in diagnostic strategies compared with currently used molecular diagnostics for patients with inoperable stage IIIB,C/IV non-squamous NSCLC from a Dutch healthcare perspective. Methods: A decision tree represented the diagnostic pathway, and a cohort state transition model represented disease progression. Three diagnostic strategies were modelled: standard of care (SoC) alone, WGS as a diagnostic test, and SoC followed by WGS. Treatment effectiveness was based on a systematic review. Probabilistic cost-effectiveness analyses were performed, and threshold analyses (using €80,000 per quality-adjusted life-year [QALY]) was used to explore the early cost effectiveness of WGS. Results: WGS as a diagnostic test resulted in more QALYs (0.002) and costs (€1534 [incremental net monetary benefit –€1349]), and SoC followed by WGS resulted in fewer QALYs (–0.002) and more costs (€1059 [–€1194]) compared with SoC alone. WGS as a diagnostic test was only cost effective if it was priced at €2000 per patient and identified 2.7% more actionable patients than SoC alone. Treating these additional identified patients with new treatments costing >€4069 per month decreased the probability of cost effectiveness. Conclusions: Our analysis suggests that providing WGS as a diagnostic test is cost effective compared with SoC followed by WGS and SoC alone if costs for WGS decrease and additional patients with actionable targets are identified. This cost-effectiveness model can be used to incorporate new findings iteratively and to support ongoing decision making regarding the use of WGS in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses. R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective. [ABSTRACT FROM AUTHOR]

Background: Much has been invested in big data and artificial intelligence-based solutions for healthcare. However, few applications have been implemented in clinical practice. Early economic evaluations can help to improve decision-making by developers of analytics underlying these solutions aiming to increase the likelihood of successful implementation, but recommendations about their use are lacking. The aim of this study was to develop and apply a framework that positions best practice methods for economic evaluations alongside development of analytics, thereby enabling developers to identify barriers to success and to select analytics worth further investments.Methods: The framework was developed using literature, recommendations for economic evaluations and by applying the framework to use cases (chronic lymphocytic leukaemia (CLL), intensive care, diabetes). First, the feasibility of developing clinically relevant analytics was assessed and critical barriers to successful development and implementation identified. Economic evaluations were then used to determine critical thresholds and guide investment decisions.Results: When using the framework to assist decision-making of developers of analytics, continuing development was not always feasible or worthwhile. Developing analytics for progressive CLL and diabetes was clinically relevant but not feasible with the data available. Alternatively, developing analytics for newly diagnosed CLL patients was feasible but continuing development was not considered worthwhile because the high drug costs made it economically unattractive for potential users. Alternatively, in the intensive care unit, analytics reduced mortality and per-patient costs when used to identify infections (- 0.5%, - €886) and to improve patient-ventilator interaction (- 3%, - €264). Both analytics have the potential to save money but the potential benefits of analytics that identify infections strongly depend on infection rate; a higher rate implies greater cost-savings.Conclusions: We present a framework that stimulates efficiency of development of analytics for big data and artificial intelligence-based solutions by selecting those applications of analytics for which development is feasible and worthwhile. For these applications, results from early economic evaluations can be used to guide investment decisions and identify critical requirements. [ABSTRACT FROM AUTHOR]

Background: Quality indicators are used to benchmark and subsequently improve quality of healthcare. However, defining good quality indicators and applying them to high-volume care such as skin cancer is not always feasible. Objectives: To determine whether claims data could be used to benchmark high-volume skin cancer care and to assess clinical practice variation. Methods: All skin cancer care-related claims in dermatology in 2016 were extracted from a nationwide claims database (Vektis) in the Netherlands. Results: For over 220,000 patients, a skin cancer diagnosis-related group was reimbursed in 124 healthcare centres. Conventional excision reflected 75% of treatments for skin cancer but showed large variation between practices. Large practice variation was also found for 5-fluorouracil and imiquimod creams. The practice variation of Mohs micrographic surgery and photodynamic therapy was low under the 75th percentile, but outliers at the 100th percentile were detected, which indicates that few centres performed these therapies far more often than average. On average, patients received 1.8 follow-up visits in 2016. Conclusions: Claims data demonstrated large practice variation in treatments and follow-up visits of skin cancer and may be a valid and feasible data set to extract quality indicators. The next step is to investigate whether detected practice variation is unwarranted and if a reduction improves quality and efficiency of care. [ABSTRACT FROM AUTHOR]

Introduction: Personalized medicine-based treatments in advanced cancer hold the promise to offer substantial health benefits to genetic subgroups, but require efficient biomarker-based patient stratification to match the right treatment and may be expensive. Standard molecular diagnostics are currently very heterogeneous, and tests are often performed sequentially. The alternative to whole genome sequencing (WGS) i.e. simultaneously testing for all relevant DNA-based biomarkers thereby allowing immediate selection of the most optimal therapy, is more costly than current techniques. In the current implementation stage, it is important to explore the added value and cost-effectiveness of using WGS on a patient level and to assess optimal introduction of WGS on the level of the healthcare system.Areas covered: First, an overview of current worldwide initiatives concerning the use of WGS in clinical practice for cancer diagnostics is given. Second, a comprehensive, early health technology assessment (HTA) approach of evaluating WGS in the Netherlands is described, relating to the following aspects: diagnostic value, WGS-based treatment decisions, assessment of long-term health benefits and harms, early cost-effectiveness modeling, nation-wide organization, and Ethical, Legal and Societal Implications.Expert opinion: This study provides evidence to guide further development and implementation of WGS in clinical practice and the healthcare system. [ABSTRACT FROM AUTHOR]

Background: Inconsistent use of generic and disease-specific health-related quality of life (HRQOL) instruments in multiple sclerosis (MS) studies limits cross-country comparability. The objectives: 1) investigate real-world HRQOL of MS patients using both generic and disease-specific HRQOL instruments in the Netherlands, France, the United Kingdom, Spain, Germany and Italy; 2) compare HRQOL among these countries; 3) determine factors associated with HRQOL.Methods: A cross-sectional, observational online web-based survey amongst MS patients was conducted in June-October 2019. Patient demographics, clinical characteristics, and two HRQOL instruments: the generic EuroQOL (EQ-5D-5L) and disease-related Multiple Sclerosis Quality of Life (MSQOL)-54, an extension of the generic Short Form-36 (SF-36) was collected. Health utility scores were calculated using country-specific value sets. Mean differences in HRQOL were analysed and predictors of HRQOL were explored in regression analyses.Results: In total 182 patients were included (the Netherlands: n = 88; France: n = 58; the United Kingdom: n = 15; Spain: n = 10; living elsewhere: n = 11). Mean MSQOL-54 physical and mental composite scores (42.5, SD:17.2; 58.3, SD:21.5) were lower, whereas the SF-36 physical and mental composite scores (46.8, SD:22.6; 53.1, SD:22.5) were higher than reported in previous clinical trials. The mean EQ-5D utility was 0.65 (SD:0.26). Cross-country differences in HRQOL were found. A common predictor of HRQOL was disability status and primary progressive MS.Conclusions: The effects of MS on HRQOL in real-world patients may be underestimated. Combined use of generic and disease-specific HRQOL instruments enhance the understanding of the health needs of MS patients. Consequent use of the same instruments in clinical trials and observational studies improves cross-country comparability of HRQOL. [ABSTRACT FROM AUTHOR]

Objectives: Important links between dietary patterns and diseases have been widely applied to establish nutrition interventions. However, knowledge about between-person heterogeneity regarding the benefits of nutrition intervention can be used to personalize the intervention and thereby improve health outcomes and efficiency. We performed a systematic review of cost-effectiveness analyses (CEAs) of interventions with a personalized nutrition (PN) component to assess their methodology and findings.Methods: A systematic search (March 2019) was performed in 5 databases: EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. CEAs involving interventions in adults with a PN component were included; CEAs focusing on clinical nutrition or undernutrition were excluded. The CHEERS checklist was used to assess the quality of CEAs.Results: We identified 49 eligible studies among 1792 unique records. Substantial variation in methodology was found. Most studies (91%) focused only on psychological concepts of PN such as behavior and preferences. Thirty-four CEAs were trial-based, 13 were modeling studies, and 4 studies were both trial- and model-based. Thirty-two studies used quality-adjusted life year as an outcome measure. Different time horizons, comparators, and modeling assumptions were applied, leading to differences in costs/quality-adjusted life years. Twenty-eight CEAs (49%) concluded that the intervention was cost-effective, and 75% of the incremental cost-utility ratios were cost-effective given a willingness-to-pay threshold of $50 000 per quality-adjusted life year.Conclusions: Interventions with PN components are often evaluated using various types of models. However, most PN interventions have been considered cost-effective. More studies should examine the cost-effectiveness of PN interventions that combine psychological and biological concepts of personalization. [ABSTRACT FROM AUTHOR]

Platinum‐based chemotherapy is not standard of care for unselected or genetically selected metastatic castration‐resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next‐generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate‐specific antigen (PSA) decline and objective radiographic response. In the wild‐type BRCA2 subgroup, 35% had a >50% PSA decline (P =.006) and 16% radiographic response (P <.001). Median overall survival was 21 months for BRCA2mut patients vs 7 months (P =.041) for those with functional BRCA2. AVPC patients demonstrated comparable responses to non‐AVPC, including a similar overall survival, despite the poor prognosis for this subgroup. In the scope of the registration of poly‐(ADP)‐ribose polymerase inhibitors (PARPi) for mCRPC, we provide initial insights on cross‐resistance between PARPi and platinum compounds. By combining the literature and our study, we identified 18 patients who received both agents. In this cohort, only BRCA2mut patients treated with platinum first (n = 4), responded to both agents. We confirm that BRCA2 inactivation is associated with meaningful responses to carboplatin, suggesting a role for both PARPi and platinum‐based chemotherapy in preselected mCRPC patients. What's new? Platinum‐based chemotherapy is not standard of care for unselected or genetically‐selected patients with metastatic castration‐resistant prostate cancer (mCRPC). However, several studies have shown that platinum‐based chemotherapy may still have a role in postponing progression in selected patient groups. This new study investigating DNA damage repair gene alterations and response to platinum‐based chemotherapy provides evidence that deep and durable responses are primarily associated with patients harbouring BRCA2 inactivation. Based on these data and the limited available literature, platinum‐based chemotherapy followed by PARP inhibition is potentially emerging as the optimal treatment sequence in pre‐selected mCRPC patients. [ABSTRACT FROM AUTHOR]

Objective: Autologous stem cell transplantation (ASCT) has improved progression‐free survival (PFS) and overall survival in eligible patients with newly diagnosed multiple myeloma (NDMM); however, relapse occurs. Maintenance therapy with lenalidomide (Len‐Mt) extends survival and delays relapse and the subsequent initiation of costly second‐line regimens. Here, we report the cost‐effectiveness of Len‐Mt following ASCT from a Dutch healthcare service perspective. Methods: A partitioned survival model was developed to assess the lifetime costs and benefits for patients with NDMM. Efficacy was taken from a pooled meta‐analysis of clinical trial data. Costs and subsequent therapy data were taken from sources appropriate for the Dutch market. Results: Lenalidomide produced a quality‐adjusted life year gain of 2.46 and a life year gain of 2.79 vs no maintenance treatment. The cost of lenalidomide was partially offset by savings of EUR 77 462 in subsequent treatment costs. The incremental cost‐effectiveness ratio of Len‐Mt vs no maintenance treatment was EUR 30 143. Key model drivers included subsequent therapies, dosing schedule, and time horizon. Conclusion: Lenalidomide is cost‐effective after ASCT vs no maintenance therapy in the Netherlands. By extending PFS, lenalidomide delays the cost burdens associated with relapse and subsequent treatment lines. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: The population of dialysis patients is ageing. Dialysis nurses are confronted with geriatric patients with multiple comorbidities. Nurses are confronted with an increasing burden of care. Objectives: The present study focused on the question of whether, over time, the increasing age and comorbidities of the haemodialysis population increased nursing care time. Furthermore, we studied potential changes in the predictors of the required nursing time. Design: Observational study. Participants: A total of 980 dialysis patients from 12 dialysis centres were included. Measurements: Nurses filled out the classification tool for each patient and completed a form for reporting patient characteristics for groups of relevant haemodialysis patients at baseline and after 1 and four years. Changes in patient and dialysis characteristics were analysed, as well as the estimated nursing care time needed. Results: An increase in the nursing time needed for dialysis was largely due to decreased mobility, closing of the vascular access and a greater need for psychosocial attention and was most strongly present in incident dialysis patients. The time needed for dialysis decreased as patient participation increased and vascular access changed from catheters to fistulae. Over the four‐year period, the average overall needed nursing care time per haemodialysis session did not change. Conclusions: Our study shows that the average nursing time needed per patient did not change in the four‐year observation period. However, more time is required for incident patients; thus, if a centre has high patient turnover, more nursing care time is needed. [ABSTRACT FROM AUTHOR]

Aims: To identify, characterize and compare all Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals that included real‐world data on efficacy from expanded access (EA) programmes. Methods: Cross‐sectional study of FDA (1955–2018) and EMA (1995–2018) regulatory approval documentation. We automated searching for terms related to EA in 22,506 documents using machine learning techniques. We included all approvals where EA terms appeared in the regulatory documentation. Our main outcome was the inclusion of EA data as evidence of clinical efficacy. Characterization was based on approval date, disease area, orphan designation and whether the evidence was supportive or pivotal. Results: EA terms appeared in 693 out of 22,506 (3.1%) documents, which referenced 187 approvals. For 39 approvals, data from EA programmes were used to inform on clinical efficacy. The yearly number of approvals with EA data increased from 1.25 for 1993–2013 to 4.6 from 2014–2018. In 13 cases, these programmes formed the main evidence for approval. Of these, patients in EA programmes formed over half (median 71%, interquartile range: 34–100) of the total patient population available for efficacy evaluation. Almost all (12/13) approvals were granted orphan designation. In 8/13, there were differences between regulators in approval status and valuation of evidence. Strikingly, 4 treatments were granted approval based solely on efficacy from EA. Conclusion: Sponsors and regulators increasingly include real‐world data from EA programmes in the efficacy profile of a treatment. The indications of the approved treatments are characterized by orphan designation and high unmet medical need. [ABSTRACT FROM AUTHOR]

Introduction: In several studies, the chimeric antigen receptor T‐cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost‐effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo‐M), clofarabine combination therapy (Clo‐C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non‐medical consumption costs. Methods: A three‐state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality‐adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost‐effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. Results: Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo‐M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo‐C (1.70) and Clo‐M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo‐C and were considered cost‐effective with a willingness‐to‐pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost‐effective. Discussion: At the current price and WTP threshold, tisagenlecleucel is cost‐effective from both a healthcare and a societal perspective. Nevertheless, long‐term effectiveness data are needed to validate the several assumptions that were necessary for this model. [ABSTRACT FROM AUTHOR]

Background: Cost-effectiveness models require quality of life utilities calculated from generic preference-based questionnaires, such as EQ-5D. We evaluated the performance of available algorithms for QLQ-C30 conversion into EQ-5D-3L based utilities in a metastatic colorectal cancer (mCRC) patient population and subsequently developed a mCRC specific algorithm. Influence of mapping on cost-effectiveness was evaluated.Methods: Three available algorithms were compared with observed utilities from the CAIRO3 study. Six models were developed using 5-fold cross-validation: predicting EQ-5D-3L tariffs from QLQ-C30 functional scale scores, continuous QLQ-C30 scores or dummy levels with a random effects model (RE), a most likely probability method on EQ-5D-3L functional scale scores, a beta regression model on QLQ-C30 functional scale scores and a separate equations subgroup approach on QLQ-C30 functional scale scores. Performance was assessed, and algorithms were tested on incomplete QLQ-C30 questionnaires. Influence of utility mapping on incremental cost/QALY gained (ICER) was evaluated in an existing Dutch mCRC cost-effectiveness model.Results: The available algorithms yielded mean utilities of 1: 0.87 ± sd:0.14,2: 0.81 ± 0.15 (both Dutch tariff) and 3: 0.81 ± sd:0.19. Algorithm 1 and 3 were significantly different from the mean observed utility (0.83 ± 0.17 with Dutch tariff, 0.80 ± 0.20 with U.K. tariff). All new models yielded predicted utilities drawing close to observed utilities; differences were not statistically significant. The existing algorithms resulted in an ICER difference of €10,140 less and €1765 more compared to the observed EQ-5D-3L based ICER (€168,048). The preferred newly developed algorithm was €5094 higher than the observed EQ-5D-3L based ICER. Disparity was explained by minimal diffences in incremental QALYs between models.Conclusion: Available mapping algorithms sufficiently accurately predict utilities. With the commonly used statistical methods, we did not succeed in developping an improved mapping algorithm. Importantly, cost-effectiveness outcomes in this study were comparable to the original model outcomes between different mapping algorithms. Therefore, mapping can be an adequate solution for cost-effectiveness studies using either a previously designed and validated algorithm or an algorithm developed in this study. [ABSTRACT FROM AUTHOR]

Objective: Much has been invested in big data analytics to improve health and reduce costs. However, it is unknown whether these investments have achieved the desired goals. We performed a scoping review to determine the health and economic impact of big data analytics for clinical decision-making.Materials and Methods: We searched Medline, Embase, Web of Science and the National Health Services Economic Evaluations Database for relevant articles. We included peer-reviewed papers that report the health economic impact of analytics that assist clinical decision-making. We extracted the economic methods and estimated impact and also assessed the quality of the methods used. In addition, we estimated how many studies assessed "big data analytics" based on a broad definition of this term.Results: The search yielded 12 133 papers but only 71 studies fulfilled all eligibility criteria. Only a few papers were full economic evaluations; many were performed during development. Papers frequently reported savings for healthcare payers but only 20% also included costs of analytics. Twenty studies examined "big data analytics" and only 7 reported both cost-savings and better outcomes.Discussion: The promised potential of big data is not yet reflected in the literature, partly since only a few full and properly performed economic evaluations have been published. This and the lack of a clear definition of "big data" limit policy makers and healthcare professionals from determining which big data initiatives are worth implementing. [ABSTRACT FROM AUTHOR]

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common type of cancer and its incidence is increasing. The objective of this study was to describe the trends in reimbursed drug and hospital costs of benign and (pre)malignant skin tumours, and to present future projections. Therefore, nationwide hospital and drug reimbursement data (for the period 2007-17) were used. In 2017, malignant skin tumours were the 4th most costly cancer in the Netherlands (after breast, colorectal, and lung cancer). The total costs for skin tumours increased from €278 million for 384,390 patients (in 2007) to €465 million for 578,355 patients (in 2017). Drug costs increased from €0.7 million to €121 million (over the period 2007-17), resulting in a 26% share of overall costs in 2017. Future costs are projected to reach €1.35 billion in 2030. In conclusion, the increasing costs of skin cancer are strongly affected by the increasing incidence and introduction of expensive drugs, and future projections are for an alarming increase. [ABSTRACT FROM AUTHOR]

Objectives: To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.Methods: A systematic review and network meta-analysis (NMA) were conducted to compare the relative efficacy of gefitinib, erlotinib, afatinib, and osimertinib in EGFR-mutated NSCLC. To assess the cost-effectiveness of these treatments, a Markov model was developed from Dutch societal perspective. The model was based on the clinical studies included in the NMA. Incremental costs per life-year (LY) and per quality-adjusted life-year (QALY) gained were estimated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted.Results: Total discounted per patient costs for gefitinib, erlotinib, afatinib, and osimertinib were €65,889, €64,035, €69,418, and €131,997, and mean QALYs were 1.36, 1.39, 1.52, and 2.01 per patient, respectively. Erlotinib dominated gefitinib. Afatinib versus erlotinib yielded incremental costs of €27,058/LY and €41,504/QALY gained. Osimertinib resulted in €91,726/LY and €128,343/QALY gained compared to afatinib. PSA showed that gefitinib, erlotinib, afatinib, and osimertinib had 13%, 19%, 43%, and 26% probability to be cost-effective at a threshold of €80,000/QALY. A price reduction of osimertinib of 30% is required for osimertinib to be cost-effective at a threshold of €80,000/QALY.Conclusions: Osimertinib has a better effectiveness compared to all other TKIs. However, at a Dutch threshold of €80,000/QALY, osimertinib appears not to be cost-effective. [ABSTRACT FROM AUTHOR]

Systematic reviews with economic components are important decision tools for stakeholders seeking to evaluate technologies, such as breast cancer screening (BCS) programs. This overview of systematic reviews explores the determinants of the cost‐effectiveness of BCS and assesses the quality of secondary evidence. The search identified 30 systematic reviews that reported on the determinants of the cost‐effectiveness of BCS, including the costs of breast cancer and BCS. While the quality of the reviews varied widely, only four out of 30 papers were considered to be of a high quality. We did not identify publication bias in the original evidence on the cost‐effectiveness of mammography screening; however, we highlight a need for improved clarity in both reporting and data verification. The reviews consisted mainly of studies from high‐income countries. Breast cancer costs varied widely among the studies. Factors leading to higher costs included: time (diagnosis and last months before death), later stage or metastases, recurrence of the disease, age below 64 years and type of follow‐up (more intensive or more specialized). Overall, screening with mammography was considered cost‐effective in the age range 50‐69 years in Western European and Northern American countries but not for older or younger women. Its cost‐effectiveness was questionable for low‐income settings and Asia. Mammography screening was more cost‐effective with biennial screening compared to annual screening and single reading using computer‐aided detection vs double reading. No information on the cost‐effectiveness of ultrasonography was found, and there is much uncertainty on the cost‐effectiveness of CBE because of methodological limitations. [ABSTRACT FROM AUTHOR]

Introduction: Clinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, this recommendation can have a dramatic impact on total drug expenditures in middle-income countries (MICs). We performed a cost-effectiveness analysis from the Iranian healthcare perspective to find an optimum duration of trastuzumab use in Iran.Method: We compared four treatment strategies comprising chemotherapy and varying durations of trastuzumab use (no trastuzumab, 6, 9 months, and 1 year), and a Markov model and probabilistic sensitivity analysis were used to estimate the costs and effects of the strategies. We then examined the cost effectiveness of the strategies at different willingness-to-pay (WTP) thresholds and ages at onset of treatment.Results: Incremental costs (versus no trastuzumab) were €8826 (6 months), €13,808 (9 months) and €18,588 (12 months), while incremental quality-adjusted life-years (QALYs) were 0.65 (6 months), 0.87 (9 months) and 1.14 (12 months). At a threshold of 3 × gross domestic product (GDP)/capita (€21,000/QALY) and for patients younger than 59 years, the 6-month protocol was most likely to be cost effective (probability of 42%). At a threshold of 4 × GDP/capita (€28,000/QALY), the 6-month and 1-year regimens were essentially equal in cost effectiveness (37 and 35%, respectively). At this WTP threshold, the 6-month and 1-year regimens were optimal strategies only for patients up to 66 and 44 years of age, respectively.Conclusion: In contrast to clinical guidelines, 6 months of trastuzumab may be the most cost-effective option for Iran. The lower absolute WTP threshold and lower life expectancy compared with high-income countries are two crucial parameters in the cost effectiveness of interventions in MICs. It is therefore necessary to strike a balance between maximum population health and maintaining affordability in these countries. [ABSTRACT FROM AUTHOR]

Background: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark.Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed.In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (−0.07, 95% CI −0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained).On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness.ClinicalTrials.gov registry (NCT04590989).Methods: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark.Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed.In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (−0.07, 95% CI −0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained).On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness.ClinicalTrials.gov registry (NCT04590989).Results: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark.Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed.In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (−0.07, 95% CI −0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained).On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness.ClinicalTrials.gov registry (NCT04590989).Conclusion: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark.Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed.In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (−0.07, 95% CI −0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained).On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness.ClinicalTrials.gov registry (NCT04590989).Trial Registration Number: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark.Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed.In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (−0.07, 95% CI −0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained).On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness.ClinicalTrials.gov registry (NCT04590989). [ABSTRACT FROM AUTHOR]

Background: Risk-sharing arrangements (RSAs) can be used to mitigate uncertainty about the value of a drug by sharing the financial risk between payer and pharmaceutical company. We evaluated the projected impact of alternative RSAs for non-small cell lung cancer (NSCLC) therapies based on real-world data.Methods: Data on treatment patterns of Dutch NSCLC patients from four different hospitals were used to perform "what-if" analyses, evaluating the costs and benefits likely associated with various RSAs. In the scenarios, drug costs or refunds were based on response evaluation criteria in solid tumors (RECIST) response, survival compared to the pivotal trial, treatment duration, or a fixed cost per patient. Analyses were done for erlotinib, gemcitabine/cisplatin, and pemetrexed/platinum for metastatic NSCLC, and gemcitabine/cisplatin, pemetrexed/cisplatin, and vinorelbine/cisplatin for nonmetastatic NSCLC.Results: Money-back guarantees led to moderate cost reductions to the payer. For conditional treatment continuation schemes, costs and outcomes associated with the different treatments were dispersed. When price was linked to the outcome, the payer's drug costs reduced by 2.5% to 26.7%. Discounted treatment initiation schemes yielded large cost reductions. Utilization caps mainly reduced the costs of erlotinib treatment (by 16%). Given a fixed cost per patient based on projected average use of the drug, risk sharing was unfavorable to the payer because of the lower than projected use. The impact of RSAs on a national scale was dispersed.Conclusions: For erlotinib and pemetrexed/platinum, large cost reductions were observed with risk sharing. RSAs can mitigate uncertainty around the incremental cost-effectiveness or budget impact of drugs, but only when the type of arrangement matches the setting and type of uncertainty. [ABSTRACT FROM AUTHOR]

Objective: No standard second‐line treatment exists for acute graft‐versus‐host disease steroid‐refractory (SR‐aGvHD), and long‐term outcomes remain poor. Mesenchymal stromal cells (MSCs) have been evaluated as treatment, but no disease model (DM) exists that integrates and extrapolates currently available evidence. The aim of this study was to develop such a DM to describe the natural history of SR‐aGvHD and to predict long‐term outcomes. Method: The DM was developed in collaboration with experts in haematology‐oncology. Subsequently, a model simulation was run. Input parameters for transition and survival estimates were informed by published data of clinical trials on MSC treatment for SR‐aGvHD. Parametric distributions were used to estimate long‐term survival rates after MSCs. Results: The newly developed DM is a cohort model that consists of eight health states. For the model simulation, we obtained data on 327 patients from 14 published phase II trials. Due to limited evidence, DM structure was simplified and several assumptions had to be made. Median overall survival was 3.2 years for complete response and 0.5 years for no complete response. Conclusion: The DM provides a comprehensive overview on the second‐line treatment pathway for aGvHD and enables long‐term predictions that can be used to perform a cost‐effectiveness analysis comparing any treatment for SR‐aGvHD. [ABSTRACT FROM AUTHOR]

Introduction: Patient registries play an important role in obtaining real-world evidence of the cost-effectiveness of treatments. However, their implementation is costly and sometimes infeasible in many middle-income countries (MICs). We explored the combination of data-mining and a large claims database to estimate the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran and the fraction of total costs from trastuzumab use. Method: We performed a retrospective analysis of claims data from the Iran Social Security Organization, a health insurer which covers approximately 50%(~40 million) of the Iranian population, in the period of 21/03/2011-20/03/2014. A data-mining algorithm using R software and validated using patient dossiers in the Cancer Research Center identified 1295 patients and divided them into the three main HER2-positive breast cancer stages (early, loco-regional and advanced). A payer perspective was used to calculate the absolute and relative direct costs of healthcare services associated with the treatment of HER2-positive breast cancer in the public and private healthcare systems. Results: The number of women totaled 802 (early), 125 (loco-regional) and 218 (advanced). The mean age[SD] was 45[], 46[] and 48[] years, respectively, while mean follow-up in all stages was approximately one year. Average costs of direct healthcare care in early, loco-regional and advanced stages were €11,796 (95%CI: €9,356-€12,498), €8,253 (95%CI: €6,843-€10,002), and €17,742 (95%CI: €15,720-€19,505), respectively. Trastuzumab accounted for the largest share of total costs in all three stages (range: 53–76%). Conclusion: Wherever comprehensive patient registries are infeasible or costly, real-world costs can be estimated through claims databases and data-mining strategies. Using this method, real-world costs have been estimated in Iran. The stage-specific cost estimates derived from this study can be used to perform real-world cost-effectiveness analyses of therapies for HER2-positive BC and support healthcare financing decisions. [ABSTRACT FROM AUTHOR]