Comparison of Timed Automata with Discrete Event Simulation for Modeling Personalized Treatment Decisions:the Case of Metastatic Castration Resistant Prostate Cancer

Objectives: The aim of this study is to compare the usefulness of two promising alternative modeling techniques, Timed Automata (TA) originating from informatics, and Discrete Event Simulation (DES) known in operations research, for modeling todays complex and personalized treatment decisions over time, involving multiple interactions and decision gates. Methods: The usefulness of both modeling techniques was assessed in a case study on the treatment of metastatic Castration Resistant Prostate Cancer (mCRPC) in which Circulating Tumor Cells (CTC) may be used as a response marker for switching first to second line treatment. Techniques were compared on user-friendliness, input requirements, input possibilities, model checking facilities, and results. Input parameters were similar for both models, consisting of costs, QoL, treatment effectiveness, diagnostic performance, physicians’ behavior and survival. Primary outcome measures were health outcomes, expressed in QALYs, and costs. Results: Modelling was considered easier using TA, as this approach allows independent modeling of the actors and elements comprising the treatment process, such as patients, physicians, tests and treatments, and their mutual interaction and communication. Furthermore, the statistical model checking feature in the TA software was found to be a powerful tool for validation. Input requirements and possibilities were similar for both modelling approaches in this case study. Both modelling approaches yield comparable results. Using TA, CTC reduced first and second line treatment by, on average, 108.9 and 107.6 days, respectively. Using DES, treatment was reduced by 83.6 and 85.0 days. CTC therefore reduced healthcare costs by €28,998 and €21,992 according to TA and DES, respectively. Conclusions: Both Timed Automata and Discrete Event Simulation seem to be suitable for modeling complex and personalized treatment processes like that of mCRPC. Timed Automata is a new and interesting alternative modeling technique, as it allows explicit separation of model components and supports statistical model checking to validate models

Cost-effectiveness of CTC guided chemo- or endocrine therapy in ER+ HER2- metastatic breast cancer – results from a randomized controlled multicenter trial

Patients with metastatic, Estrogen Receptor (ER) positive, HER2-negative, breast cancer, before initiating CDK4/6 inhibitors, receive either single agent endocrine- or chemotherapy based on their clinical risk. In this first-ever trial-based economic evaluation of Circulating Tumor Cells (CTCs), the cost-effectiveness of standardizing the prescription of endocrine- or chemotherapy using a CTC count threshold (with >5 CTCs/7.5mL indicative of unfavorable disease outcomes) was compared to current clinical practice. N=755 ER+ HER2-patients, enrolled in 17 French centres, were randomized to CTC guided or standard of care and were treated according to either through the CTC score or clinical examination. Health state utilities were calculated by mapping the QLQ-C30 to EQ-5D utilities and used to calculate Quality-Adjusted Life Years (QALY) over a 2-year time horizon. Bootstrapping and additional sensitivity analyses were performed to quantify the impact of uncertainty. Health outcomes in both arms were similar, but costs were higher in the CTC guided arm (€19,403) compared to the usual care (€18,254), resulting in an ICER of €104,078/QALY in favor of usual care. However, when the analysis was performed for the clinically high- and low-risk groups separately, CTC enumeration could be a dominant strategy (cost saving) if treatment is de-escalated in clinically high-risk patients as indicated by CTC scores. However, the current analysis was based on the PFS and OS data reported in 2021 and long-term Overall Survival data is collected since then (JCO, 2023 in press). A further analysis of the health economic impact of CTC enumeration in clinically low and high-risk groups is therefore indicated

Value of information analytical methods: Report 2 of the ISPOR value of information analysis emerging good practices task force

The allocation of health care resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities, and on the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision-making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using Value of Information (VOI) analysis. This report, from the ISPOR VOI Task Force, describes methods for computing four VOI measures: the Expected Value of Perfect Information (EVPI), Expected Value of Partial Perfect Information (EVPPI), Expected Value of Sample Information (EVSI) and Expected Net Benefit of Sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Contains fulltext : 220851.pdf (Publisher’s version ) (Open Access)OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. Design: A cross-sectional study. Participants: 200 women aged >45 with PCOS, and 200 age-matched controls. Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P <.001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P <.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning lon

Parental education and adult health outcomes: a cohort study examining disease-specific effects of education levels using Swedish nationwide registries across two generations

It is well known that children with less educated parents have inferior health status in later life. There are two competing hypotheses explaining the association found: the pathway hypothesis – suggesting that children from low educated households are more likely to obtain less education themselves, which, in turn, is associated with inferior health outcomes – and the life course hypothesis – suggesting that living conditions during childhood, as such affected by parental education level, is important for the formation of adult health status. We obtained data from National Swedish registries comprising health outcomes of individuals born between 1940 and 1949, and the Swedish Multi-generation Register. We assessed the differences in risk of hospital admission for individuals with low and high parental education as well as low and high own education. We found that for higher educated individuals, high parental education is associated with even better health outcomes: having a high versus low educated mother or high versus low educated father was associated with an overall decrease in the risk (hazard rate) of hospital admission by 5% (95% CI 0.91-0.98) and 3% (95% CI 0.95-0.99), respectively. This indicates that children from a relatively disadvantaged background, signaled by lower parental educational attainment, are more likely to continue accumulating risk throughout life. Even if they have higher qualifications they may still have a greater accumulation of risk, compared with other highly qualified children from a less disadvantaged background. We found that this effect is primarily attributed to circulatory diseases, and would appear to support the life course hypothesis. We conclude that parental education and ensuing early childhood or even fetal living conditions have a persistent effect on adult health