Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial.

BACKGROUND: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRASG12C. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation who had been previously treated with other anticancer drugs. METHODS: We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries. We recruited patients aged at least 18 years with KRASG12C-mutated advanced NSCLC, who progressed after previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Key exclusion criteria included new or progressing untreated brain lesions or symptomatic brain lesions, previously identified oncogenic driver mutation other than KRASG12C for which an approved therapy is available (eg EGFR or ALK), previous treatment with docetaxel (neoadjuvant or adjuvant docetaxel was allowed if the tumour did not progress within 6 months after the therapy was terminated), previous treatment with a direct KRASG12C inhibitor, systemic anticancer therapy within 28 days of study day 1, and therapeutic or palliative radiation therapy within 2 weeks of treatment initiation. We randomly assigned (1:1) patients to oral sotorasib (960 mg once daily) or intravenous docetaxel (75 mg/m2 once every 3 weeks) in an open-label manner using interactive response technology. Randomisation was stratified by number of previous lines of therapy in advanced disease (1 vs 2 vs >2), ethnicity (Asian vs non-Asian), and history of CNS metastases (present or absent). Treatment continued until an independent central confirmation of disease progression, intolerance, initiation of another anticancer therapy, withdrawal of consent, or death, whichever occurred first. The primary endpoint was progression-free survival, which was assessed by a blinded, independent central review in the intention-to-treat population. Safety was assessed in all treated patients. This trial is registered at ClinicalTrials.gov, NCT04303780, and is active but no longer recruiting. FINDINGS: Between June 4, 2020, and April 26, 2021, 345 patients were randomly assigned to receive sotorasib (n=171 [50%]) or docetaxel (n=174 [50%]). 169 (99%) patients in the sotorasib group and 151 (87%) in the docetaxel group received at least one dose. After a median follow-up of 17·7 months (IQR 16·4-20·1), the study met its primary endpoint of a statistically significant increase in the progression-free survival for sotorasib, compared with docetaxel (median progression-free survival 5·6 months [95% CI 4·3-7·8] vs 4·5 months [3·0-5·7]; hazard ratio 0·66 [0·51-0·86]; p=0·0017). Sotorasib was well tolerated, with fewer grade 3 or worse (n=56 [33%] vs n=61 [40%]) and serious treatment-related adverse events compared with docetaxel (n=18 [11%] vs n=34 [23%]). For sotorasib, the most common treatment-related adverse events of grade 3 or worse were diarrhoea (n= 20 [12%]), alanine aminotransferase increase (n=13 [8%]), and aspartate aminotransferase increase (n=9 [5%]). For docetaxel, the most common treatment-related adverse events of grade 3 or worse were neutropenia (n=13 [9%]), fatigue (n=9 [6%]), and febrile neutropenia (n=8 [5%]). INTERPRETATION: Sotorasib significantly increased progression-free survival and had a more favourable safety profile, compared with docetaxel, in patients with advanced NSCLC with the KRASG12C mutation and who had been previously treated with other anticancer drugs. FUNDING: Amgen.

The cost-effectiveness of UGT1A1 genotyping before colorectal cancer treatment with irinotecan from the perspective of the German statutory health insurance.

BACKGROUND: The evidence concerning the cost-effectiveness of UGT1A1*28 genotyping is ambiguous and does not allow drawing valid conclusions for Germany. This study evaluates the cost-effectiveness of UGT1A1 genotyping in patients with metastatic colorectal cancer undergoing irinotecan-based chemotherapy compared to no testing from the perspective of the German statutory health insurance. MATERIAL AND METHODS: A decision-analytic Markov model with a life time horizon was developed. No testing was compared to two genotype-dependent therapy strategies: 1) dose reduction by 25%; and 2) administration of a prophylactic G-CSF growth factor analog for homozygous and heterozygous patients. Probability, quality of life and cost parameters used in this study were based on published literature. Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Strategy 1 dominated all remaining strategies. Compared to no testing, it resulted in only marginal QALY increases (0.0002) but a cost reduction of €580 per patient. Strategy 2 resulted in the same health gains but increased costs by €10 773. In the probabilistic analysis, genotyping and dose reduction was the optimal strategy in approximately 100% of simulations at a threshold of €50 000 per QALY. Deterministic sensitivity analysis shows that uncertainty for this strategy originated primarily from costs for irinotecan-based chemotherapy, from the prevalence of neutropenia among heterozygous patients, and from whether dose reduction is applied to both homozygotes and heterozygotes or only to the former. CONCLUSION: This model-based synthesis of the most recent evidence suggests that pharmacogenetic UGT1A1 testing prior to irinotecan-based chemotherapy dominates non-personalized colon cancer care in Germany. However, as structural uncertainty remains high, these results require validation in clinical practice, e.g. based on a managed-entry agreement.

Economic evaluation of genetic screening for Lynch syndrome in Germany.

PURPOSE: Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. METHODS: We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically. RESULTS: On average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was [euro ]77,268, [euro ]253,258, and [euro ]4,188,036 per life-year gained, respectively. CONCLUSION: The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.

Communicating the parameter uncertainty in the IQWiG efficiency frontier to decision-makers.

The Institute for Quality and Efficiency in Health Care (IQWiG) developed-in a consultation process with an international expert panel-the efficiency frontier (EF) approach to satisfy a range of legal requirements for economic evaluation in Germany's statutory health insurance system. The EF approach is distinctly different from other health economic approaches. Here, we evaluate established tools for assessing and communicating parameter uncertainty in terms of their applicability to the EF approach. Among these are tools that perform the following: (i) graphically display overall uncertainty within the IQWiG EF (scatter plots, confidence bands, and contour plots) and (ii) communicate the uncertainty around the reimbursable price. We found that, within the EF approach, most established plots were not always easy to interpret. Hence, we propose the use of price reimbursement acceptability curves-a modification of the well-known cost-effectiveness acceptability curves. Furthermore, it emerges that the net monetary benefit allows an intuitive interpretation of parameter uncertainty within the EF approach. This research closes a gap for handling uncertainty in the economic evaluation approach of the IQWiG methods when using the EF. However, the precise consequences of uncertainty when determining prices are yet to be defined.

The cost-utility of open prostatectomy compared with active surveillance in early localised prostate cancer.

BACKGROUND: There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. METHODS: A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. RESULTS: With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of €6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of €96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. CONCLUSION: AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients' valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences.

Should health insurers target prevention of cardiovascular disease? A cost-effectiveness analysis of an individualised programme in Germany based on routine data.

BACKGROUND: Cardiovascular diseases are the main cause of death worldwide, making their prevention a major health care challenge. In 2006, a German statutory health insurance company presented a novel individualised prevention programme (KardioPro), which focused on coronary heart disease (CHD) screening, risk factor assessment, early detection and secondary prevention. This study evaluates KardioPro in CHD risk subgroups, and analyses the cost-effectiveness of different individualised prevention strategies. METHODS: The CHD risk subgroups were assembled based on routine data from the statutory health insurance company, making use of a quasi-beta regression model for risk prediction. The control group was selected via propensity score matching based on logistic regression and an approximate nearest neighbour approach. The main outcome was cost-effectiveness. Effectiveness was measured as event-free time, and events were defined as myocardial infarction, stroke and death. Incremental cost-effectiveness ratios comparing participants with non-participants were calculated for each subgroup. To assess the uncertainty of results, a bootstrapping approach was applied. RESULTS: The cost-effectiveness of KardioPro in the group at high risk of CHD was € 20,901 per event-free year; in the medium-risk group, € 52,323 per event-free year; in the low-risk group, € 186,074 per event-free year; and in the group with known CHD, € 26,456 per event-free year. KardioPro was associated with a significant health gain but also a significant cost increase. However, statistical significance could not be shown for all subgroups. CONCLUSION: The cost-effectiveness of KardioPro differs substantially according to the group being targeted. Depending on the willingness-to-pay, it may be reasonable to only offer KardioPro to patients at high risk of further cardiovascular events. This high-risk group could be identified from routine statutory health insurance data. However, the long-term consequences of KardioPro still need to be evaluated.

Cost effectiveness of external hip protectors in the hospital setting: a modeling study.

Chronic illnesses, for which many patients are admitted to hospitals, substantially increase the risk of falling, and hence the likelihood of incurring a hip fracture. Hip fractures not only have devastating consequences on an individual's quality of life but may also affect a hospital's reputation in the community. In addition, hospitals may face litigation claims and increased costs for patients who fall and suffer a major injury as a consequence. External hip protectors are comparable to padded undergarments and shield the trochanter, reducing the detrimental effects and force impacting the bone during a fall. Screening for patients at high risk of falling and providing high-risk patients with hip protectors as a preventive measure to avoid hip fractures, not only improves public health, but can also save hospitals care and litigation costs.

Effects of a nurse-based case management compared to usual care among aged patients with myocardial infarction: results from the randomized controlled KORINNA study.

BACKGROUND: Transition from hospital to home is a critical period for older persons with acute myocardial infarction (AMI). Home-based secondary prevention programs led by nurses have been proposed to facilitate the patients' adjustment to AMI after discharge. The objective of this study was to evaluate the effects of a nurse-based case management for elderly patients discharged after an AMI from a tertiary care hospital. METHODS: In a single-centre randomized two-armed parallel group trial of patients aged 65 years and older hospitalized with an AMI between September 2008 and May 2010 in the Hospital of Augsburg, Germany, patients were randomly assigned to a case management or a control group receiving usual care. The case-management intervention consisted of a nurse-based follow-up for one year including home visits and telephone calls. Key elements of the intervention were to detect problems or risks and to give advice regarding a wide range of aspects of disease management (e.g. nutrition, medication). Primary study endpoint was time to first unplanned readmission or death. Block randomization per telephone call to a biostatistical center, where the randomization list was kept, was performed. Persons who assessed one-year outcomes and validated readmission data were blinded. Statistical analysis was based on the intention-to-treat approach and included Cox Proportional Hazards models. RESULTS: Three hundred forty patients were allocated to receive case-management (n=168) or usual care (n=172). The analysis is based on 329 patients (intervention group: n=161; control group: n=168). Of these, 62% were men, mean age was 75.4 years, and 47.1% had at least either diabetes or chronic heart failure as a major comorbidity. The mean follow-up time for the intervention group was 273.6 days, and for the control group it was 320.6 days. During one year, in the intervention group there were 57 first unplanned readmissions and 5 deaths, while the control group had 75 first unplanned readmissions and 3 deaths. With respect to the endpoint there was no significant effect of the case management program after one year (Hazard Ratio 1.01, 95% confidence interval 0.72-1.41). This was also the case among subgroups according to sex, diabetes, living alone, and comorbidities. CONCLUSIONS: A nurse-based management among elderly patients with AMI had no significant influence on the rate of first unplanned readmissions or death during a one-year follow-up. A possible long-term influence should be investigated by further studies. CLINICAL TRIAL REGISTRATION: ISRCTN02893746.

Validity, reliability and responsiveness of the EQ-5D in German stroke patients undergoing rehabilitation.

PURPOSE: To analyse the psychometric properties of the EQ-5D in German stroke survivors undergoing neurological rehabilitation. METHODS: The EQ-5D, the Hospital Anxiety and Depression Scale (HADS) and the Stroke Impact Scale (SIS) were completed before (210 subjects) and after (183 subjects) a patient education programme in seven rehabilitation clinics in Bavaria, Germany. A postal follow-up was conducted after 6 months. Acceptance, validity, reliability and responsiveness of the EQ-5D were tested. The SIS subscales were used as external anchors to classify the patients into change groups between the measurements. RESULTS: The proportion of missing answers ranged from 4.7 to 8.6%. Between 16 and 19% reported no problems in any EQ-5D dimension. At baseline, correlations between EQ-5D index and the SIS subscales ranged from 0.15 (communication) to 0.60 (mobility). Correlations with the EQ VAS were slightly smaller. All scores were reliable in test-retest with intraclass correlations ranging from 0.67 to 0.81. EQ-5D index and EQ VAS were consistently responsive only to improvements in health, showing small- to medium effect sizes (0.27-0.42). CONCLUSIONS: The EQ-5D has shown reasonable validity, reliability and, more limited, responsiveness in stroke patients with mild to moderate limitations of functional status, allowing it to be used in clinical trials in rehabilitation.

A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting.

BACKGROUND: Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective. OBJECTIVES: To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective. METHODS: Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting. RESULTS: Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively. CONCLUSIONS: Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women at very high risk of fracture in Canada.

This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis at very high risk for fracture in Canada. Results showed that romosozumab sequenced to alendronate is a cost-effective treatment option, dominating both alendronate and risedronate alone. PURPOSE: To demonstrate the value of romosozumab sequenced to alendronate compared to alendronate or risedronate alone, for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture and who are at very high risk for future fracture in Canada. METHODS: A Markov model followed a hypothetical cohort of postmenopausal osteoporotic women at very high risk for future fractures, to estimate the cost-effectiveness of romosozumab and alendronate compared to oral bisphosphonates alone. A total treatment period of 5 years was assumed. Quality-adjusted life years and costs were estimated for each comparator across health states defined by different types of fragility fractures. RESULTS: Romosozumab/alendronate was associated with a lifetime gain of 0.103 and 0.127 QALYs and a cost reduction of $343 and $3805, relative to alendronate and risedronate, respectively. These results were driven by a reduction of the number of fractures (2561 per 1000 patients, versus 2700 for alendronate and 2724 for risedronate over lifetime). Romosozumab/alendronate had the highest probability of being cost-effective, relative to alendronate and risedronate, at any willingness to pay threshold value. CONCLUSION: Romosozumab/alendronate was associated with reduced costs and greater benefit relative to other comparators. Probabilistic, deterministic, and scenario analyses indicate that romosozumab/alendronate represents the best value for money; the uncertainty analyses are robust, and therefore romosozumab should be considered for reimbursement by public drug plans in Canada .

A Proposal of a Cost-Effectiveness Modeling Approach for Heart Failure Treatment Assessment: Considering the Short- and Long-Term Impact of Hospitalization on Event Rates.

BACKGROUND: The rate of events such as recurrent heart failure (HF) hospitalization and death are known to dramatically increase directly after HF hospitalization. Furthermore, the number of HF hospitalizations is associated with irreversible long-term disease progression, which is in turn associated with increased event rates. However, cost-effectiveness models of HF treatments commonly fail to capture both the short- and long-term association between HF hospitalization and events. OBJECTIVE: The aim of this study was to provide a decision-analytic model that reflects the short- and long-term association between HF hospitalization and event rates. Furthermore, we assess the impact of omitting these associations. METHODS: We developed a life-time Markov cohort model to evaluate HF treatments, and modeled the short-term impact of HF hospitalization on event rates via a sequence of tunnel states, with transition probabilities following a parametric survival curve. The corresponding long-term impact was modeled via hazard ratios per HF hospitalization. We obtained baseline event rates and utilities from published literature. Subsequently, we assessed, for a hypothetical HF treatment, how omitting the modeled associations (through a simple two-state model) affects incremental quality-adjusted life-years (QALYs). RESULTS: We developed a model that incorporates both short- and long-term impacts of HF hospitalizations. Based on an assumed treatment effect of a 20% risk reduction for HF hospitalization (and associated reductions in all-cause mortality of 15%), omitting the short-term, the long-term, or both associations resulted in a 5%, 1%, and 22% decrease in QALYs gained, respectively. CONCLUSION: For both modeling components, i.e., the short- and long-term implications of HF hospitalization, the impact on incremental outcomes associated with treatment was substantial. Considering these aspects as proposed within this modeling approach better reflects the natural course of this progressive condition and will enhance the evaluation of future HF treatments.

Real-world cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis in Taiwan.

This study assessed the cost-effectiveness of continued denosumab treatment, compared with discontinuation of denosumab after one dose, for the treatment of postmenopausal osteoporosis in Taiwan, using real-world fracture reduction effectiveness and cost data. Outcomes indicate that continued denosumab treatment produces an incremental cost-effectiveness ratio of USD $16,743 per QALY. PURPOSE: To evaluate the cost-effectiveness of continued denosumab use versus discontinuation after one dose, for the treatment of postmenopausal osteoporosis in Taiwan, using real-world fracture reduction effectiveness and cost data. METHODS: A Markov cohort model was used to evaluate the lifetime costs and QALYs associated with continued denosumab treatment versus discontinuation of treatment after one dose. The evaluation was conducted from the perspective of Taiwan's healthcare system and used a discount rate of 3% per annum. The patient population consisted of postmenopausal women with osteoporosis with a mean age of 77 years who initiated denosumab treatment. Fracture reduction effectiveness data, baseline fracture rates, mortality data, and costs of fracture were informed by Taiwan's National Health Insurance Research Database. RESULTS: Model outcomes showed that continued treatment with denosumab produced an expected gain of 0.042 QALYs and an incremental cost of USD $704, compared with discontinuation of denosumab after one dose. This corresponds to an incremental cost-effectiveness ratio of USD $16,743 per QALY gained. Probabilistic and scenario analysis showed that results are stable to variations in model assumptions and parameters. CONCLUSION: In a real-world setting, at a cost per QALY threshold equivalent to gross domestic product per capita in 2020 in Taiwan (USD $30,038), continued treatment with denosumab in postmenopausal women with osteoporosis is cost-effective compared with treatment discontinuation.

Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: a health technology assessment report.

OBJECTIVES: The aim of this study was to compare the predictive value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs-CRP)-screening in addition to traditional risk factor screening in apparently healthy persons as a means of preventing coronary artery disease. METHODS AND RESULTS: The systematic review was performed according to internationally recognized methods. Seven studies on risk prediction, one clinical decision-analytic modeling study, and three decision-analytic cost-effectiveness studies were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to 2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models increased the areas under the curve by 0.00 to 0.027. Based on the clinical decision analysis, both individuals with elevated hs-CRP-levels and those with hyperlipidemia have a similar gain in life expectancy following statin therapy. One high-quality economic modeling study suggests favorable incremental cost-effectiveness ratios for persons with elevated hs-CRP and higher risk. However, many model parameters were based on limited evidence. CONCLUSIONS: Adding hs-CRP to traditional risk factors improves risk prediction, but the clinical relevance and cost-effectiveness of this improvement remain unclear.

Economic modeling of risk-adapted screen-and-treat strategies in women at high risk for breast or ovarian cancer.

BACKGROUND: The 'German Consortium for Hereditary Breast and Ovarian Cancer' (GC-HBOC) offers women with a family history of breast and ovarian cancer genetic counseling. The aim of this modeling study was to evaluate the cost-effectiveness of genetic testing for BRCA 1/2 in women with a high familial risk followed by different preventive interventions (intensified surveillance, risk-reducing bilateral mastectomy, risk-reducing bilateral salpingo-oophorectomy, or both mastectomy and salpingo-oophorectomy) compared to no genetic test. METHODS: A Markov model with a lifelong time horizon was developed for a cohort of 35-year-old women with a BRCA 1/2 mutation probability of ≥ 10%. The perspective of the German statutory health insurance (SHI) was adopted. The model included the health states 'well' (women with increased risk), 'breast cancer without metastases', 'breast cancer with metastases', 'ovarian cancer', 'death', and two post (non-metastatic) breast or ovarian cancer states. Outcomes were costs, quality of life years gained (QALYs) and life years gained (LYG). Important data used for the model were obtained from 4380 women enrolled in the GC-HBOC. RESULTS: Compared with the no test strategy, genetic testing with subsequent surgical and non-surgical treatment options provided to women with deleterious BRCA 1 or 2 mutations resulted in additional costs of €7256 and additional QALYs of 0,43 (incremental cost-effectiveness ratio of €17,027 per QALY; cost per LYG: €22,318). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSION: The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.

Sex differences in treatment patterns of six chronic diseases: an analysis from the German statutory health insurance.

OBJECTIVE: The goal of this study was to investigate gender-specific differences in prevalence, healthcare costs, and treatment patterns in the German Statutory Health Insurance (SHI). METHODS: The study analyzed administrative claims data of over 26 million insured with respect to prevalence and cost of illness of six chronic diseases. Insured were identified using the ATC code for medication prescription and ICD-9 code for diagnosis. The influences of gender, age, and comorbidity on cost differences were analyzed via multivariate regression analysis. RESULTS: Adjusted for age and comorbidity, gender had a significant influence on both hospital and medication spending. Hospital costs on average were 17.1% (95% CI 14.1; 20.2) higher for men compared with women. Medication spending for men exceeded that for women on average by 13.8% (95% CI 10.9; 16.7). The diagnoses with the highest prevalence were hypertension and heart failure. Women had a higher prevalence of diabetes, coronary artery disease (CAD), heart failure, and hypertension. Medication costs were higher for men in three of five diagnoses and comparable for two diagnoses (diabetes and asthma). Women received more medication prescriptions than men, but on average prescriptions for men were 14%-26% more expensive than prescriptions for women. Regarding treatment patterns men were treated with different drug classes in cardiovascular disease (CVD) compared with women. Total medication spending stratified by diagnosis was highest for diabetes. CONCLUSIONS: Gender differences for costs and prescribing patterns for chronic diseases vary disease specifically, but generally men had higher inpatient costs and more expensive medication prescriptions, whereas women had higher numbers of prescriptions.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.

Cost-effectiveness of different strategies to prevent breast and ovarian cancer in German women with a BRCA 1 or 2 mutation.

BACKGROUND: Women with a BRCA1 or BRCA2 mutation are at increased risk of developing breast and/or ovarian cancer. This economic modeling study evaluated different preventive interventions for 30-year-old women with a confirmed BRCA (1 or 2) mutation. METHODS: A Markov model was developed to estimate the costs and benefits [i.e., quality-adjusted life years (QALYs), and life years gained (LYG)] associated with prophylactic bilateral mastectomy (BM), prophylactic bilateral salpingo-oophorectomy (BSO), BM plus BSO, BM plus BSO at age 40, and intensified surveillance. Relevant input data was obtained from a large German database including 5902 women with BRCA 1 or 2, and from the literature. The analysis was performed from the German Statutory Health Insurance (SHI) perspective. In order to assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed. RESULTS: With costs of €29,434 and a gain in QALYs of 17.7 (LYG 19.9), BM plus BSO at age 30 was less expensive and more effective than the other strategies, followed by BM plus BSO at age 40. Women who were offered the surveillance strategy had the highest costs at the lowest gain in QALYs/LYS. In the probabilistic sensitivity analysis, the probability of cost-saving was 57% for BM plus BSO. At a WTP of 10,000 € per QALY, the probability of the intervention being cost-effective was 80%. CONCLUSIONS: From the SHI perspective, undergoing BM plus immediate BSO should be recommended to BRCA 1 or 2 mutation carriers due to its favorable comparative cost-effectiveness.

Costs and effects of intra-operative fluorescence molecular imaging - A model-based, early assessment.

INTRODUCTION: Successful breast conserving cancer surgeries come along with tumor free resection margins and account for cosmetic outcome. Positive margins increase the likelihood of tumor recurrence. Intra-operative fluorescence molecular imaging (IFMI) aims to focus surgery on malignant tissue thus substantially lowering the presence of positive margins as compared with standard techniques of breast conservation (ST). A goal of this paper is to assess the incremental number of surgeries and costs of IFMI vs. ST. METHODS: We developed a decision analytical model and applied it for an early evaluation approach. Given uncertainty we considered that IFMI might reduce the proportion of positive margins found by ST from all to none and this proportion is assumed to be reduced to 10% for the base case. Inputs included data from the literature and a range of effect estimates. For the costs of IFMI, respective cost components were added to those of ST. RESULTS: The base case reduction lowered number of surgeries (mean [95% confidence interval]) by 0.22 [0.15; 0.30] and changed costs (mean [95% confidence interval]) by €-663 [€-1,584; €50]. A tornado diagram identified the Diagnosis Related Group (DRG) costs, the proportion of positive margins of ST, the staff time saving factor and the duration of frozen section analysis (FSA) as important determinants of this cost. CONCLUSIONS: These early results indicate that IFMI may be more effective than ST and through the reduction of positive margins it is possible to save follow-up surgeries-indicating further health risk-and to save costs through this margin reduction and the avoidance of FSA.

Exploring the potential value of improved care for secondary hyperparathyroidism with a novel calcimimetic therapy.

AIMS: This study explored the use of a value-based pricing approach for the new calcimimetic etelcalcetide indicated for the treatment of secondary hyperparathyroidism (SHPT) in patients receiving hemodialysis. It used the US payer perspective and applied the cost-effectiveness framework. Because etelcalcetide is an intravenous therapy that can be titrated for individual patients, and because its utilization is yet to be assessed in real world settings, a range of plausible doses were estimated for etelcalcetide to define a range of prices. These were either in relation to the existing oral calcimimetic cinacalcet or compared to no calcimimetic treatment. MATERIALS AND METHODS: The value-based price of etelcalcetide was determined via a Markov model. This model combined data from the etelcalcetide trials and previously published cost-effectiveness models in SHPT, and allowed extrapolation of treatment effects on mortality, cardiovascular events, fracture, and parathyroidectomy. Several dosing scenarios were explored covering the dose ranges of 30.0-64.18 mg per day for cinacalcet and 1.07-3.11 mg per day for etelcalcetide. These included the mean dose from the etelcalcetide trials, the preliminary defined daily dose, and the expected most common dose in real world. An acceptable price range for etelcalcetide was assessed by comparing the incremental cost-effectiveness ratios obtained with the willingness-to-pay threshold range of $100,000-$300,000/quality-adjusted life-years. RESULTS: Cost-effectiveness analysis supported value-based prices for etelcalcetide ranging from $21.15-$49.97/mg vs cinacalcet, and $13.79-$119.45/mg vs no calcimimetics. LIMITATIONS: There is uncertainty around what the real-world dosing will be for etelcalcetide. Another important nuance is that no studies have examined etelcalcetide effects on hard outcomes and, therefore, this modeling exercise relied on an extrapolation approach. CONCLUSIONS: This cost-effectiveness analysis, including scenarios to address uncertainties, allowed estimation of a value-based price range to aid reimbursement decisions in the US.