Economic evaluation of adjuvant therapy with osimertinib in patients with early-stage non-small cell lung cancer and mutated EGFR.

PURPOSE: The ADAURA trial demonstrated the superiority of osimertinib over a placebo with regard to disease-free survival, showing it to be indicated as an adjuvant therapy for treatment of non-small cell lung cancer with mutated epidermal growth factor receptor (EGFR). The aim of the present study was to conduct a cost-utility analysis and an analysis of the budgetary impact of adjuvant therapy with osimertinib in patients with non-small cell lung cancer with mutated EGFR who had undergone resection surgery with curative intent. METHODS: Analyses were based on the outcomes of the ADAURA clinical trial and were conducted through a Spanish National Health Service perspective. The outcome measures used were quality-adjusted life years (QALY). RESULTS: The average overall cost of adjuvant treatment with osimertinib over a period of 100 months in the overall sample of trial patients (stages IB-IIIA) was 220,961 €, compared with 197,849 € in the placebo group. Effectiveness, estimated according to QALY, was 6.26 years in the osimertinib group and 5.96 years in the placebo group, with the incremental cost-utility ratio being 77,040 €/QALY. With regard to the budgetary impact, it was estimated that, in 2021, approximately 1130 patients would be subsidiaries to receive osimertinib. This pertains to a difference of 17,375,330 € over 100 months to fund this treatment relative to no treatment. CONCLUSION: Taking into account a Spanish threshold of 24,000 €/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 10%, to obtain a cost-effective alternative.

The duration of intervals on the oral cancer care pathway and implications for survival: a systematic review and meta-analysis.

Introduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31-73), k = 18, of the diagnosis interval 35 days (95% CI = 21-38), k = 11, and of the treatment interval 30 days (95% CI = 23-53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.

The cost-effectiveness of a uniform versus age-based threshold for one-off screening for prevention of cardiovascular disease.

The objective of this article was to assess the cost-effectiveness of screening strategies for cardiovascular diseases (CVD). A decision analytic model was constructed to estimate the costs and benefits of one-off screening strategies differentiated by screening age, sex and the threshold for initiating statin therapy ("uniform" or "age-adjusted") from the Spanish NHS perspective. The age-adjusted thresholds were configured so that the same number of people at high risk would be treated as under the uniform threshold. Health benefit was measured in quality-adjusted life years (QALY). Transition rates were estimated from the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD), a large multicentre nested case-cohort study with 12 years of follow-up. Unit costs of primary care, hospitalizations and CVD care were taken from the Spanish health system. Univariate and probabilistic sensitivity analyses were employed. The comparator was no systematic screening program. The base case model showed that the most efficient one-off strategy is to screen both men and women at 40 years old using a uniform risk threshold for initiating statin treatment (Incremental Cost-Effectiveness Ratio of €3,274/QALY and €6,085/QALY for men and women, respectively). Re-allocating statin treatment towards younger individuals at high risk for their age and sex would not offset the benefit obtained using those same resources to treat older individuals. Results are sensitive to assumptions about CVD incidence rates. To conclude, one-off screening for CVD using a uniform risk threshold appears cost-effective compared with no systematic screening. These results should be evaluated in clinical studies.

Duration of the patient interval in breast cancer and factors associated with longer delays in low-and middle-income countries: A systematic review with meta-analysis.

OBJECTIVE: Breast cancer survival is lower in low- and middle-income countries (LMICs) partially due to many women being diagnosed with late-stage disease. The patient interval refers to the time elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta-analysis of the duration of the patient interval in LMICs and investigate the socio-demographic and socio-cultural factors related to longer delays in presentation. METHODS: We conducted a systematic review with meta-analysis (pre-registered protocol CRD42020200752). We searched seven information sources (2009-2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs. RESULTS: The longest patient intervals were reported in studies from the Middle East (3-4 months), followed by South-East Asia (2 months), Africa (1-2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio-economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South-East Asia, and Africa and distrust in the healthcare system in Eastern Europe. CONCLUSIONS: There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.

The patient, diagnostic, and treatment intervals in adult patients with cancer from high- and lower-income countries: A systematic review and meta-analysis.

BACKGROUND: Longer time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries. METHODS AND FINDINGS: We conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days [95% CI 52 to 85], e.g., myelomas (83 days [47 to 145])), genitourinary (58 days [50 to 77], e.g., prostate (85 days [57 to 112])), and digestive/gastrointestinal (57 days [45 to 67], e.g., colorectal (63 days [48 to 78])) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days [45 to 66], e.g., prostate (75 days [61 to 87])) and gynecological (46 days [38 to 54], e.g., cervical (69 days [45 to 108]) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered. CONCLUSIONS: These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information.

Development of the European Healthcare and Social Cost Database (EU HCSCD) for use in economic evaluation of healthcare programs.

INTRODUCTION: Costs are one of the critical factors for the transferability of the results in health technology assessment and economic evaluation. The objective is to develop a cost database at the European level to facilitate cross-border cost comparisons in different settings and explains the factors that lead to differences in healthcare costs in different countries, taking into account the differences between health systems and other factors. METHODOLOGY: The core of the database is compounded of three main categories (primary resources, composite goods and services, and complex processes and interventions) organized into 13 subcategories. A number of elements providing as detailed information of unit cost as possible were identified in order to mitigate the problem of comparability. Consortium partners validated both the database structure and selected costing items. RESULTS: Twenty-seven costing items included in the EU HCSCD resulted in 1450 unit costs when taking into account all item subtypes and countries. Cross-country differences in costs are driven by the type of resources included in the costing items (e.g., overhead costs in case of complex processes and interventions) or by the variety of existing brands and/or models and the type of unit value in most of the primary resources. CONCLUSION: The EU HCSCD is the only public unit healthcare and social cost database at European level that gather data on unit costs and explains differences in costs across countries. Its maintenance and regular data updating will enable establishing specific systems for generating and recording information that will meet many of its current limitations.

Description of day case costs and tariffs of cataract surgery from a sample of nine European countries.

BACKGROUND: The lack of transparency in the methodology of unit cost estimation and the usage of confidential or undisclosed information prevents cost comparisons and makes the transferability of the results across countries difficult. The objective of this article is to compare the methodologies used in the estimation of the cost of a day case cataract extirpation that are described in the official and publicly available sources and to study how these translate into different unit cost estimates. METHODS: A literature review was conducted to identify the main sources of unit costs of cataract extirpation. A semi-structured questionnaire to obtain information on national costing methodologies was developed and sent to consortium partners in nine European countries. Additionally, publicly available sources of unit cost of cataract surgery in those countries included in the European Healthcare and Social Cost Database (EU HCSCD) were analysed. RESULTS: The findings showed a considerable diversity across countries on unit costs varying from 432.5€ in Poland (minor degree of severity) to 3411.96€ in Portugal (major degree of severity). In addition, differences were found in the year of cost publication and on the level of detail of different types of cataract surgery. The unit of activity were Diagnosis-Related Groups in all countries except Slovenia. All unit costs include direct costs and variable overheads (except Germany where nursing costs are financed separately). Differences were identified in the type of fixed overheads included in unit costs. Methodological documents explaining the identification, measurement and evaluation of resources included in the unit costs, as well as use of appropriate cost drivers are publicly available only in England, Portugal and Sweden. CONCLUSIONS: We can conclude that while unit costs of cataract extirpation are publicly available, the information on methodological aspects is scarce. This appears to pose a significant problem for cross-country comparisons of costs and transferability of results from one country to another.

Are costs derived from diagnosis-related groups suitable for use in economic evaluations? A comparison across nine European countries in the European Healthcare and Social Cost Database.

BACKGROUND: Economic evaluation of health technologies requires healthcare resources, procedures and services to be valued at their opportunity cost. In practice, many economic evaluation studies use official databases of hospital Diagnosis-Related Groups (DRGs) as inputs where unit costs are required. This study describes the available data on costs of hospital DRG from official, publicly available sources in nine European countries (England, France, Germany, Italy, Poland, Portugal, Slovenia, Spain and Sweden), critically examines and compares the methodologies used to construct these databases and comments on the appropriateness of such unit cost data for economic evaluation. METHODS: A standardized semi-structured questionnaire was developed in order to obtain both official publicly available sources of inpatient DRG databases and documents explaining the costing methodology used in calculation of unit costs available in those databases. RESULTS: England stands out as a benchmark in terms of good practice. Other countries face more challenges in one or more items, whether in documenting and auditing processes, guaranteeing methodological rigour, including all relevant economic items such as depreciation of buildings and equipment and capital costs, conducting the process annually and completely, publishing the costs as well as tariffs and recognising sampling uncertainty or variation. CONCLUSION: Analysts should evaluate carefully whether DRG costs or tariffs published in each country are appropriate for use in economic evaluation.

Costing methodologies in European economic evaluation guidelines: commonalities and divergences.

From both the methodological point of view and standardization of methodology, little attention has been paid to the estimation of direct costs in evaluation of healthcare technologies. The objective is to revise the recommendations on direct costs provided in European economic evaluation guidelines and to identify the commonalities and divergences among them. To achieve this, a comprehensive search through several online databases was performed resulting in 41 documents from 26 European countries, be they economic evaluation guidelines or costing guidelines. The results show a large disparity in methodologies used in estimation of direct costs to be included in economic evaluations of health technologies recommended by European countries. A lack of standardization of cost estimation methodologies influences arbitrariness in selecting costs of resources included in economic evaluations of medicinal products or any other technologies and, therefore, in decision making process necessary to introduce new technology. In addition, this heterogeneity poses a major challenge for identifying factors that could affect the variability of unit costs across countries.

Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain.

Breast cancer is one of the most frequent malignancies. The aim of the article is to analyse the cost-utility ratio and budgetary impact of talazoparib treatment for patients with locally advanced or metastatic gBRCA + breast cancer from the perspective of the Spanish National Health System. Analyses were based on the EMBRACA clinical trial and the model was constructed according to "partitioned survival analysis". Two scenarios were considered in order to compare talazoparib with the alternatives of capecitabine, vinorelbine and eribulin: 1. Chemotherapy in patients pre-treated with anthracyclines/taxanes and, 2. A second- and subsequent-line treatment option. Treatment types following relapse were recorded in the mentioned clinical trial. The effectiveness measure used was quality-adjusted life years (QALY). The average health cost of patients treated at 43 months with talazoparib was 84,360.86€, whilst current treatment costs were 26,683.90€. The effectiveness of talazoparib was 1.93 years of survival (1.09 QALY) relative to 1.58 years (0.83 QALY) in the treatment group. The incremental cost-utility ratio was 252,420.04€/QALY. This represents the additional cost required to earn an additional QALY when changing from regular treatment to talazoparib. Regarding budgetary impact, the number of patients susceptible to receiving treatment with between 94 and 202 talazoparib was estimated, according to scenario and likelihood. The 3-year cost difference was between 6.9 and 9 million euros. The economic evaluation conducted shows an elevated incremental cost-utility ratio and budgetary impact. Taking these results into account, the price of talazoparib would have to be lower than that taken as a reference to reach the cost-utility thresholds.

A general framework for classifying costing methods for economic evaluation of health care.

According to the most traditional economic evaluation manuals, all "relevant" costs should be included in the economic analysis, taking into account factors such as the patient population, setting, location, year, perspective and time horizon. However, cost information may be designed for other purposes. Health care organisations may lack sophisticated accounting systems and consequently, health economists may be unfamiliar with cost accounting terminology, which may lead to discrepancy in terms used in the economic evaluation literature and management accountancy. This paper identifies new tendencies in costing methodologies in health care and critically comments on each included article. For better clarification of terminology, a pragmatic glossary of terms is proposed. A scoping review of English and Spanish language literature (2005-2018) was conducted to identify new tendencies in costing methodologies in health care. The databases PubMed, Scopus and EconLit were searched. A total of 21 studies were included yielding 43 costing analysis. The most common analysis was top-down micro-costing (49%), followed by top-down gross-costing (37%) and bottom-up micro-costing (14%). Resource data were collected prospectively in 12 top-down studies (32%). Hospital database was the most common way of collection of resource data (44%) in top-down gross-costing studies. In top-down micro-costing studies, the most resource use data collection was the combination of several methods (38%). In general, substantial inconsistencies in the costing methods were found. The convergence of top-down and bottom-up methods may be an important topic in the next decades.

Cost-effectiveness of a primary care-based exercise intervention in perimenopausal women. The FLAMENCO Project / Análisis de coste-efectividad de un programa de ejercicio físico en mujeres perimenopáusicas. Proyecto FLAMENCO

OBJECTIVE: Adequate physical activity levels and a healthy lifestyle may prevent all kinds of non-communicable diseases, promote well-being and reduce health-care costs among perimenopausal women. This study assessed an exercise programme for perimenopausal women. METHOD: A total of 150 women (aged 45-64 years) not engaged in regular physical activity were randomly assigned to either a 16 week exercise intervention or to the control group. The study was conducted from the perspective of the National Health System. Health outcomes were quality-adjusted life years (QALYs), measured by the EuroQol-5D-5L questionnaire. The total direct costs of the programme were the costs of visits to primary care, specialty care, emergency, medicines, instructor cost and infrastructure cost. The results were expressed as the incremental cost-effectiveness ratio. Sensitivity analysis was undertaken to test the robustness of the analysis. RESULTS: Mean QALYs over 16 weeks were.228 in the control group and.230 in the intervention group (mean difference: .002; 95% confidence interval [95%CI]: -0.005 to 0.009). Improvements from baseline were greater in the intervention group in all dimensions of the EuroQol-5D-5L but not statistically significant. The total costs at the end of the intervention were 160.38 € in the control group and 167.80 € in the intervention group (mean difference: 7.42 €; 95%CI: -47 to 62). The exercise programme had an incremental cost-effectiveness ratio of 4,686 €/QALY. CONCLUSIONS: The programme could be considered cost-effective, although the overall difference in health benefits and costs was very modest. Longer term follow-up is needed

OBJETIVO: El ejercicio físico puede promover el bienestar y reducir los costes de atención médica en las mujeres perimenopáusicas. Este estudio evalúa un programa de ejercicio físico en mujeres perimenopáusicas. MÉTODO: Un total de 150 mujeres (de edades comprendidas entre 45 y 64 años) fueron asignadas aleatoriamente al grupo de intervención o al grupo de control. El estudio ha tenido una duración de 16 semanas. Los resultados en salud se han medido en años de vida ajustados por calidad (AVAC) mediante el cuestionario EuroQol-5D-5L. Se ha considerado el total de costes directos del programa, integrado por los costes de las visitas en atención primaria, atención especializada y urgencias, medicamentos, coste del monitor y coste de las instalaciones. Los resultados se han expresado como ratio coste-efectividad incremental. La robustez del modelo se ha contrastado con un análisis de sensibilidad. RESULTADOS: Al final de la intervención, los AVAC fueron 0,228 en el grupo de control y 0,230 en el grupo de intervención (diferencia media: 0,002; intervalo de confianza del 95% [IC95%]: -0,005 a 0,009). La mejoría fue mayor en el grupo de intervención en todas las dimensiones del EuroQol-5D-5L, pero sin significación estadística. Los costes totales al finalizar la intervención han sido de 160,38 € en el grupo de control y 167,80 € en el de intervención (diferencia media: 7,42 €; IC95%: -47 a 62). El programa de ejercicio físico ha tenido una ratio coste-efectividad incremental de 4686 €/AVAC. CONCLUSIÓN: El programa debe considerarse coste-efectivo, aunque la diferencia en resultados de salud y costes ha sido muy moderada. Se necesita un seguimiento a más largo plazo

Cost-effectiveness of a primary care-based exercise intervention in perimenopausal women. The FLAMENCO Project.

OBJECTIVE: Adequate physical activity levels and a healthy lifestyle may prevent all kinds of non-communicable diseases, promote well-being and reduce health-care costs among perimenopausal women. This study assessed an exercise programme for perimenopausal women. METHOD: A total of 150 women (aged 45-64 years) not engaged in regular physical activity were randomly assigned to either a 16 week exercise intervention or to the control group. The study was conducted from the perspective of the National Health System. Health outcomes were quality-adjusted life years (QALYs), measured by the EuroQol-5D-5L questionnaire. The total direct costs of the programme were the costs of visits to primary care, specialty care, emergency, medicines, instructor cost and infrastructure cost. The results were expressed as the incremental cost-effectiveness ratio. Sensitivity analysis was undertaken to test the robustness of the analysis. RESULTS: Mean QALYs over 16 weeks were.228 in the control group and.230 in the intervention group (mean difference: .002; 95% confidence interval [95%CI]: -0.005 to 0.009). Improvements from baseline were greater in the intervention group in all dimensions of the EuroQol-5D-5L but not statistically significant. The total costs at the end of the intervention were 160.38 € in the control group and 167.80 € in the intervention group (mean difference: 7.42 €; 95%CI: -47 to 62). The exercise programme had an incremental cost-effectiveness ratio of 4,686 €/QALY. CONCLUSIONS: The programme could be considered cost-effective, although the overall difference in health benefits and costs was very modest. Longer term follow-up is needed.

Cost-effectiveness of an exercise intervention program in perimenopausal women: the Fitness League Against MENopause COst (FLAMENCO) randomized controlled trial.

BACKGROUND: The high prevalence of women that do not reach the recommended level of physical activity is worrisome. A sedentary lifestyle has negative consequences on health status and increases health care costs. The main objective of this project is to assess the cost-effectiveness of a primary care-based exercise intervention in perimenopausal women. METHODS/DESIGN: The present study is a Randomized Controlled Trial. A total of 150 eligible women will be recruited and randomly assigned to either a 16-week exercise intervention (3 sessions/week), or to usual care (control) group. The primary outcome measure is the incremental cost-effectiveness ratio. The secondary outcome measures are: i) socio-demographic and clinical information; ii) body composition; iii) dietary patterns; iv) glycaemic and lipid profile; v) physical fitness; vi) physical activity and sedentary behaviour; vii) sleep quality; viii) quality of life, mental health and positive health; ix) menopause symptoms. All outcomes will be assessed at baseline and post intervention. The data will be analysed on an intention-to-treat basis and per protocol. In addition, we will conduct a cost effectiveness analysis from a health system perspective. DISCUSSION: The intervention designed is feasible and if it proves to be clinically and cost effective, it can be easily transferred to other similar contexts. Consequently, the findings of this project might help the Health Systems to identify strategies for primary prevention and health promotion as well as to reduce health care requirements and costs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02358109. Date of registration: 05/02/2015.