Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102.

PURPOSE: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101.

BMT CTN 1101 was a Phase III randomized controlled trial comparing reduced-intensity conditioning followed by double unrelated umbilical cord blood transplantation (UCBT) versus HLA-haploidentical related donor bone marrow transplantation (haplo-BMT) for patients with high-risk hematologic malignancies. Here we report the results of a parallel cost-effectiveness analysis of these 2 hematopoietic stem cell transplantation (HCT) techniques. In this study, 368 patients were randomized to unrelated UCBT (n = 186) or haplo-BMT (n = 182). We estimated healthcare utilization and costs using propensity score-matched haplo-BMT recipients from the OptumLabs Data Warehouse for trial participants age <65 years and Medicare claims for participants age ≥65 years. Weibull models were used to estimate 20-year survival. EQ-5D surveys by trial participants were used to estimate quality-adjusted life-years (QALYs). At a 5-year follow-up, survival was 42% for haplo-BMT recipients versus 36% for UCBT recipients (P = .06). Over a 20-year time horizon, haplo-BMT is expected to be more effective (+.63 QALY) and more costly (+$118,953) for persons age <65 years. For those age ≥65 years, haplo-BMT is expected to be more effective and less costly. In one-way uncertainty analyses, for persons age <65, the cost per QALY result was most sensitive to life-years and health state utilities, whereas for those age ≥65, life- years were more influential than costs and health state utilities. Compared to UCBT, haplo-BMT was moderately more cost-effective for patients age <65 years and less costly and more effective for persons age ≥65 years. Haplo-BMT is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BMT is a preferred choice when considering costs and outcomes.

Cost-Effectiveness Analysis of a Procalcitonin-Guided Decision Algorithm for Antibiotic Stewardship Using Real-World U.S. Hospital Data.

Medical decision-making is revolutionizing with the introduction of artificial intelligence and machine learning. Yet, traditional algorithms using biomarkers to optimize drug treatment continue to be important and necessary. In this context, early diagnosis and rational antimicrobial therapy of sepsis and lower respiratory tract infections (LRTI) are vital to prevent morbidity and mortality. In this study we report an original cost-effectiveness analysis (CEA) of using a procalcitonin (PCT)-based decision algorithm to guide antibiotic prescription for hospitalized sepsis and LRTI patients versus standard care. We conducted a CEA using a decision-tree model before and after the implementation of PCT-guided antibiotic stewardship (ABS) using real-world U.S. hospital-specific data. The CEA included societal and hospital perspectives with the time horizon covering the length of hospital stay. The main outcomes were average total costs per patient, and numbers of patients with Clostridium difficile and antibiotic resistance (ABR) infections. We found that health care with the PCT decision algorithm for hospitalized sepsis and LRTI patients resulted in shorter length of stay, reduced antibiotic use, fewer mechanical ventilation days, and lower numbers of patients with C. difficile and ABR infections. The PCT-guided health care resulted in cost savings of $25,611 (49% reduction from standard care) for sepsis and $3630 (23% reduction) for LRTI, on average per patient. In conclusion, the PCT decision algorithm for ABS in sepsis and LRTI might offer cost savings in comparison with standard care in a U.S. hospital context. To the best of our knowledge, this is the first health economic analysis on PCT implementation using U.S. real-world data. We suggest that future CEA studies in other U.S. and worldwide settings are warranted in the current age when PCT and other decision algorithms are increasingly deployed in precision therapeutics and evidence-based medicine.

Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation.

BACKGROUND: An emerging immunotherapy is infusion of tumor infiltrating Lymphocytes (TIL), with objective response rates of around 50% versus 19% for ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly personalized and complex therapy. It requests substantial upfront investments from the hospital in: expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics. Therefore, an early health economic modelling study, as part of a Coverage with Evidence Development (CED) program, was performed. METHODS: We used a Markov decision model to estimate the expected costs and outcomes (quality-adjusted life years; QALYs) for TIL versus ipilimumab for second line treatment in metastatic melanoma patients from a Dutch health care perspective over a life long time horizon. Three mutually exclusive health states (stable disease (responders)), progressive disease and death) were modelled. To inform further research prioritization, Value of Information (VOI) analysis was performed. RESULTS: TIL is expected to generate more QALYs compared to ipilimumab (0.45 versus 0.38 respectively) at lower incremental cost (presently €81,140 versus €94,705 respectively) resulting in a dominant ICER (less costly and more effective). Based on current information TIL is dominating ipilimumab and has a probability of 86% for being cost effective at a cost/QALY threshold of €80,000. The Expected Value of Perfect Information (EVPI) amounted to €3 M. CONCLUSIONS: TIL is expected to have the highest probability of being cost-effective in second line treatment for advanced melanoma compared to ipilimumab. To reduce decision uncertainty, a clinical trial investigating e.g. costs and survival seems most valuable. This is currently being undertaken as part of a CED program in the Netherlands Cancer Institute, Amsterdam, the Netherlands, in collaboration with Denmark.

Shifting breast cancer surveillance from current hospital setting to a community based setting: a cost-effectiveness study.

BACKGROUND: This study explores the effectiveness and cost-effectiveness of surveillance after breast cancer treatment provided in a hospital-setting versus surveillance embedded in the community-based National Breast Cancer Screening Program (NBCSP). METHODS: Using a decision tree, strategies were compared on effectiveness and costs from a healthcare perspective over a 5-year time horizon. Women aged 50-75 without distant metastases that underwent breast conserving surgery in 2003-2006 were selected from the Netherlands Cancer Registry (n = 14,093). Key input parameters were mammography sensitivity and specificity, risk of loco regional recurrence (LRR), and direct healthcare costs. Primary outcome measure was the proportion true test results (TTR), expressed as the positive and negative predictive value (PPV, NPV). The incremental cost-effectiveness ratio (ICER) is defined as incremental costs per TTR forgone. RESULTS: For the NBCSP-strategy, 13,534 TTR (8 positive; 13,526 negative), and 12,923 TTR (387 positive; 12,536 negative) were found for low and high risks respectively. For the hospital-based strategy, 26,663 TTR (13 positive; 26,650 negative) and 24,883 TTR (440 positive; 24,443 negative) were found for low and high risks respectively. For low risks, the PPV and NPV for the NBCSP-based strategy were 3.31% and 99.88%, and 2.74% and 99.95% for the hospital strategy respectively. For high risks, the PPV and NPV for the NBCSP-based strategy were 64.10% and 98.87%, and 50.98% and 99.71% for the hospital-based strategy respectively. Total expected costs of the NBCSP-based strategy were lower than for the hospital-based strategy (low risk: €1,271,666 NBCSP vs €2,698,302 hospital; high risk: €6,939,813 NBCSP vs €7,450,150 hospital), rendering ICERs that indicate cost savings of €109 (95%CI €95-€127) (low risk) and €43 (95%CI €39-€56) (high risk) per TTR forgone. CONCLUSION: Despite expected cost-savings of over 50% in the NBCSP-based strategy, it is nearly 50% lower accurate than the hospital-based strategy, compromising the goal of early detection of LRR to an extent that is unlikely to be acceptable.

Value of Implementation of Strategies to Increase the Adherence of Health Professionals and Cancer Survivors to Guideline-Based Physical Exercise.

BACKGROUND: To increase the adherence of health professionals and cancer survivors to evidence-based physical exercise, effective implementation strategies (ISTs) are required. OBJECTIVES: To examine to what extent these ISTs provide value for money and which IST has the highest expected value. METHODS: The net benefit framework of health economic evaluations is used to conduct a value-of-implementation analysis of nine ISTs. Seven are directed to health professionals and two to cancer survivors. The analysis consists of four steps: 1) analyzing the expected value of perfect implementation (EVPIM); 2) assessing the estimated costs of the various ISTs; 3) comparing the ISTs' costs with the EVPIM; and 4) assessing the total net benefit (TNB) of the ISTs. These steps are followed to identify which strategy has the greatest value. RESULTS: The EVPIM for physical exercise in the Netherlands is €293 million. The total costs for the ISTs range from €34,000 for printed educational materials for professionals to €120 million for financial incentives for patients, and thus all are cost-effective. The TNB of the ISTs that are directed to professionals ranges from €5.7 million for printed educational materials to €30.9 million for reminder systems. Of the strategies that are directed to patients, only the motivational program had a positive net benefit of €100.4 million. CONCLUSIONS: All the ISTs for cancer survivors, except for financial incentives, had a positive TNB. The largest improvements in adherence were created by a motivational program for patients, followed by a reminder system for professionals.

A SYSTEMATIC APPROACH FOR ASSESSING, IN THE ABSENCE OF FULL EVIDENCE, WHETHER MULTICOMPONENT INTERVENTIONS CAN BE MORE COST-EFFECTIVE THAN SINGLE COMPONENT INTERVENTIONS.

OBJECTIVES: Multicomponent interventions (MCIs), consisting of at least two interventions, are common in rehabilitation and other healthcare fields. When the effectiveness of the MCI versus that of its single interventions is comparable or unknown, evidence of their expected incremental cost-effectiveness can be helpful in deciding which intervention to recommend. As such evidence often is unavailable this study proposes an approach to estimate what is more cost-effective; the MCI or the single intervention(s). METHODS: We reviewed the literature for potential methods. Of those identified, headroom analysis was selected as the most suitable basis for developing the approach, based on the criteria of being able to estimate the cost-effectiveness of the single interventions versus that of the MCI (a) within a limited time frame, (b) in the absence of full data, and (c) taking into account carry-over and interaction effects. We illustrated the approach with an MCI for cancer survivors. RESULTS: The approach starts with analyzing the costs of the MCI. Given a specific willingness-to-pay-value, it is analyzed how much effectiveness the MCI would need to generate to be considered cost-effective, and if this is likely to be attained. Finally, the cost-effectiveness of the single interventions relative to the potential of the MCI for being cost-effective can be compared. CONCLUSIONS: A systematic approach using headroom analysis was developed for estimating whether an MCI is likely to be more cost effective than one (or more) of its single interventions.

(Very) Early technology assessment and translation of predictive biomarkers in breast cancer.

Predictive biomarkers can guide treatment decisions in breast cancer. Many studies are undertaken to discover and translate these biomarkers, yet few biomarkers make it to practice. Before use in clinical decision making, predictive biomarkers need to demonstrate analytical validity, clinical validity and clinical utility. While attaining analytical and clinical validity is relatively straightforward, by following methodological recommendations, the achievement of clinical utility is extremely challenging. It requires demonstrating three associations: the biomarker with the outcome (prognostic association), the effect of treatment independent of the biomarker, and the differential treatment effect between the prognostic and the predictive biomarker (predictive association). In addition, economical, ethical, regulatory, organizational and patient/doctor-related aspects are hampering the translational process. Traditionally, these aspects do not receive much attention until formal approval or reimbursement of a biomarker test (informed by Health Technology Assessment (HTA)) is at stake, at which point the clinical utility and sometimes price of the test can hardly be influenced anymore. When HTA analyses are performed earlier, during biomarker research and development, they may prevent further development of those biomarkers unlikely to ever provide sufficient added value to society, and rather facilitate translation of the promising ones. Early HTA is particularly relevant for the predictive biomarker field, as expensive medicines are under pressure and the need for biomarkers to guide their appropriate use is huge. Closer interaction between clinical researchers and HTA experts throughout the translational research process will ensure that available data and methodologies will be used most efficiently to facilitate biomarker translation.

Cost-effectiveness and resource use of implementing MRI-guided NACT in ER-positive/HER2-negative breast cancers in The Netherlands.

BACKGROUND: Response-guided neoadjuvant chemotherapy (RG-NACT) with magnetic resonance imaging (MRI) is effective in treating oestrogen receptor positive/human epidermal growth factor receptor-2 negative (ER-positive/HER2-negative) breast cancer. We estimated the expected cost-effectiveness and resources required for its implementation compared to conventional-NACT. METHODS: A Markov model compared costs, quality-adjusted-life-years (QALYs) and costs/QALY of RG-NACT vs. conventional-NACT, from a hospital perspective over a 5-year time horizon. Health services required for and health outcomes of implementation were estimated via resource modelling analysis, considering a current (4 %) and a full (100 %) implementation scenario. RESULTS: RG-NACT was expected to be more effective and less costly than conventional NACT in both implementation scenarios, with 94 % (current) and 95 % (full) certainty, at a willingness to pay threshold of €20.000/QALY. Fully implementing RG-NACT in the Dutch target population of 6306 patients requires additional 5335 MRI examinations and an (absolute) increase in the number of MRI technologists, by 3.6 fte (full-time equivalent), and of breast radiologists, by 0.4 fte. On the other hand, it prevents 9 additional relapses, 143 cancer deaths, 23 congestive heart failure events and 2 myelodysplastic syndrome/acute myeloid leukaemia events. CONCLUSION: Considering cost-effectiveness, RG-NACT is expected to dominate conventional-NACT. While personnel capacity is likely to be sufficient for a full implementation scenario, MRI utilization needs to be intensified.

Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.

OBJECTIVES: To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis. METHODS: A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions. We assessed the expected value of partial perfect information, the expected value of sample information, and the expected net benefit of sampling for potential ancillary studies of an ongoing randomized controlled trial (RCT; NCT01057069). RESULTS: The expected value of partial perfect information indicated that further research should be prioritized to the parameter group including "biomarkers' prevalence, positive predictive value (PPV), and treatment response rates (TRRs) in biomarker-negative patients and patients with TNBC" (€639 million), followed by utilities (€48 million), costs (€40 million), and transition probabilities (TPs) (€30 million). By setting up four ancillary studies to the ongoing RCT, data on 1) TP and MLPA prevalence, PPV, and TRR; 2) aCGH and aCGH/MLPA plus XIST and 53BP1 prevalence, PPV, and TRR; 3) utilities; and 4) costs could be simultaneously collected (optimal size = 3000). CONCLUSIONS: Further research on predictive biomarkers for HDAC should focus on gathering data on TPs, prevalence, PPV, TRRs, utilities, and costs from the four ancillary studies to the ongoing RCT.

Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients.

PURPOSE: Guiding response to neoadjuvant chemotherapy (guided-NACT) allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial). MATERIALS AND METHODS: As effectiveness was shown in hormone-receptor positive (HR+) early breast cancers (EBC), our decision model compared the health-economic outcomes of treating a cohort of such women with guided-NACT to conventional-NACT using clinical input data from the GeparTrio trial. The expected cost-effectiveness and the uncertainty around this estimate were estimated via probabilistic cost-effectiveness analysis (CEA), from a Dutch societal perspective over a 5-year time-horizon. RESULTS: Our exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY) cost-effectiveness was expected with 78% certainty. CONCLUSION: This exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial) is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.

Comparative cost-effectiveness of focal and total salvage 125I brachytherapy for recurrent prostate cancer after primary radiotherapy.

PURPOSE: Focal salvage (FS) iodine 125 (125I) brachytherapy could be an effective treatment for locally radiorecurrent prostate cancer (PCa). Toxicity is often reduced compared to total salvage (TS) while cancer control can be maintained, which could increase cost-effectiveness. The current study estimates the incremental cost per quality-adjusted life year (QALY) of FS compared to TS. MATERIAL AND METHODS: A decision analytic Markov model was developed, which compares costs and QALYs associated with FS and TS. A 3-year time horizon was adopted with six month cycles, with a hospital perspective on costs. Probabilities for genitourinary (GU) and gastrointestinal (GI) toxicity and their impact on health-related quality of life (SF-36) were derived from clinical studies in the University Medical Center Utrecht (UMCU). Probabilistic sensitivity analysis, using 10,000 Monte Carlo simulations, was performed to quantify the joint decision uncertainty up to the recommended maximum willingness-to-pay threshold of €80,000/QALY. RESULTS: Focal salvage dominates TS as it results in less severe toxicity and lower treatment costs. Decision uncertainty is small, with a 97-100% probability for FS to be cost-effective compared to TS (€0-€80,000/QALY). Half of the difference in costs between FS and TS was explained by higher treatment costs of TS, the other half by higher incidence of severe toxicity. One-way sensitivity analyses show that model outcomes are most sensitive to utilities and probabilities for severe toxicity. CONCLUSIONS: Focal salvage 125I brachytherapy dominates TS, as it has lower treatment costs and leads to less toxicity in our center. Larger comparative studies with longer follow-up are necessary to assess the exact influence on (biochemical disease free) survival and toxicity.

A cost-effectiveness analysis of using TheraBite in a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy.

Previous studies have shown that a "Preventive Exercise Program" (PREP) is cost-effective compared to the standard exercise program provided in "Usual Care" (UC) in patients with advanced head and neck cancer. The current paper specifically estimates the cost-effectiveness of the TheraBite jaw rehabilitation device (TB) which is used as part of the PREP, compared to Speech Language Pathology (SLP) sessions as part of UC, and herewith intents to inform reimbursement discussions regarding the TheraBite device. Costs and outcomes [quality-adjusted life-years (QALYs)] of the TB compared to SLP were estimated using a Markov model of advanced head and neck cancer patients. Secondary outcome variables were trismus, feeding substitutes, facial pain, and pneumonia. The incremental cost-effectiveness ratio (ICER) was estimated from a health care perspective of the Netherlands, with a time horizon of 2 years. The total health care costs per patient were estimated to amount to €5,129 for the TB strategy and €6,915 for the SLP strategy. Based on the current data, the TB strategy yielded more quality-adjusted life-years (1.28) compared to the SLP strategy (1.24). Thus, the TB strategy seems more effective (+0.04) and less costly (-€1,786) than the SLP only strategy. At the prevailing threshold of €20,000/QALY the probability for the TB strategy being cost-effective compared to SLP was 70 %. To conclude, analysis of presently available data indicates that TB is expected to be cost-effective compared to SLP in a preventive exercise program for concomitant chemo-radiotherapy for advanced head and neck cancer patients.

Return-to-work intervention for cancer survivors: budget impact and allocation of costs and returns in the Netherlands and six major EU-countries.

BACKGROUND: Return-to-work (RTW)-interventions support cancer survivors in resuming work, but come at additional healthcare costs. The objective of this study was to assess the budget impact of a RTW-intervention, consisting of counselling sessions with an occupational physician and an exercise-programme. The secondary objective was to explore how the costs of RTW-interventions and its financial revenues are allocated among the involved stakeholders in several EU-countries. METHODS: The budget impact (BI) of a RTW-intervention versus usual care was analysed yearly for 2015-2020 from a Dutch societal- and from the perspective of a large cancer centre. The allocation of the expected costs and financial benefits for each of the stakeholders involved was compared between the Netherlands, Belgium, England, France, Germany, Italy, and Sweden. RESULTS: The average intervention costs in this case were €1,519/patient. The BI for the Netherlands was €-14.7 m in 2015, rising to €-71.1 m in 2020, thus the intervention is cost-saving as the productivity benefits outweigh the intervention costs. For cancer centres the BI amounts to €293 k in 2015, increasing to €1.1 m in 2020. Across European countries, we observed differences regarding the extent to which stakeholders either invest or receive a share of the benefits from offering a RTW-intervention. CONCLUSION: The RTW-intervention is cost-saving from a societal perspective. Yet, the total intervention costs are considerable and, in many European countries, mainly covered by care providers that are not sufficiently reimbursed.

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy.

PURPOSE: Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard chemotherapy. Additionally, we estimated the minimum required prevalence of BRCA1-like and the required positive predictive value (PPV) for a BRCA1-like test to become cost-effective. METHODS: Our Markov model compared 1) the incremental costs; 2) the incremental number of respondents; 3) the incremental number of Quality Adjusted Life Years (QALYs); and 4) the incremental cost-effectiveness ratio (ICER) of treating TNBC women with personalized HDAC based on BRCA1-like testing vs. standard chemotherapy, from a Dutch societal perspective and a 20-year time horizon, using probabilistic sensitivity analysis. Furthermore, we performed one-way sensitivity analysis (SA) to all model parameters, and two-way SA to prevalence and PPV. Data were obtained from a current trial (NCT01057069), published literature and expert opinions. RESULTS: BRCA1-like testing to target effective HDAC would presently not be cost-effective at a willingness-to-pay threshold of €80.000/QALY (€81.981/QALY). SAs show that PPV drives the ICER changes. Lower bounds for the prevalence and the PPV were found to be 58.5% and 73.0% respectively. CONCLUSION: BRCA1-like testing to target effective HDAC treatment in TNBC patients is currently not cost-effective at a willingness-to-pay of €80.000/QALY, but it can be when a minimum PPV of 73% is obtained in clinical practice. This information can help test developers and clinicians in decisions on further research and development of BRCA1-like tests.

Cost-effectiveness of heat and moisture exchangers compared to usual care for pulmonary rehabilitation after total laryngectomy in Poland.

The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore, a model-based cost-effectiveness analysis of using HMEs versus usual care (UC) (including stoma covers, suction system and/or external humidifier) for patients after laryngectomy was performed. Primary outcomes were costs, QALYs and incremental cost-effectiveness ratio (ICER). Secondary outcomes were pulmonary infections, and sleeping problems. The analysis was performed from a health care perspective of Poland, using a time horizon of 10 years and cycle length of 1 year. Transition probabilities were derived from various sources, amongst others a Polish randomized clinical trial. Quality of life data was derived from an Italian study on similar patients. Data on frequencies and mortality-related tracheobronchitis and/or pneumonia were derived from a Europe-wide survey amongst head and neck cancer experts. Substantial differences in quality-adjusted survival between the use of HMEs (3.63 QALYs) versus UC (2.95 QALYs) were observed. Total health care costs/patient were 39,553 PLN (9465 Euro) for the HME strategy and 4889 PLN (1168 Euro) for the UC strategy. HME use resulted in fewer pulmonary infections, and less sleeping problems. We could conclude that given the Polish threshold of 99,000 PLN/QALY, using HMEs is cost-effective compared to UC, resulting in 51,326 PLN/QALY (12,264 Euro/QALY) gained for patients after total laryngectomy. For the hospital period alone (2 weeks), HMEs were cost-saving: less costly and more effective.

Cost-effectiveness of cognitive behavioral therapy and physical exercise for alleviating treatment-induced menopausal symptoms in breast cancer patients.

PURPOSE: Many breast cancer patients experience (severe) menopausal symptoms after an early onset of menopause caused by cancer treatment. The aim of this study was to assess the cost-effectiveness of cognitive behavioral therapy (CBT) and physical exercise (PE), compared to a waiting list control group (WLC). METHODS: We performed a cost-effectiveness analysis from a healthcare system perspective, using a Markov model. Effectiveness data came from a recent randomized controlled trial that evaluated the efficacy of CBT and PE. Cost data were obtained from relevant Dutch sources. Outcome measures were incremental treatment costs (ITCs) per patient with a clinically relevant improvement on a measure of endocrine symptoms, the Functional Assessment of Cancer Therapy questionnaire (FACT-ES), and on a measure of hot flushes, the Hot Flush Rating Scale (HFRS), and costs per quality-adjusted life years (QALY) gained over a 5-year time period. RESULTS: ITCs for achieving a clinically relevant decline on the FACT-ES for one patient were €1,051 for CBT and €1,315 for PE, compared to the WLC. The corresponding value for the HFRS was €1,067 for CBT, while PE was not more effective than the WLC. Incremental cost-utility ratios were €22,502/QALY for CBT and €28,078/QALY for PE. CONCLUSION: CBT is likely the most cost-effective strategy for alleviating treatment-induced menopausal symptoms in this population, followed by PE. The outcomes are sensitive to a reduction of the assumed duration of the treatment effect from 5 to 3 and 1.5 years. IMPLICATIONS FOR CANCER SURVIVORS: Patients can be prescribed CBT or, based on individual preferences, PE.

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: a retrospective study regarding toxicity, biochemical outcome and quality of life.

PURPOSE: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. MATERIALS AND METHODS: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. RESULTS: With a median follow-up of 36 months (range 10-45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. CONCLUSION: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable.

Belief elicitation to populate health economic models of medical diagnostic devices in development.

BACKGROUND AND OBJECTIVE: Bayesian methods can be used to elicit experts' beliefs about the clinical value of healthcare technologies. This study investigates a belief-elicitation method for estimating diagnostic performance in an early stage of development of photoacoustic mammography (PAM) imaging versus magnetic resonance imaging (MRI) for detecting breast cancer. RESEARCH DESIGN: Eighteen experienced radiologists ranked tumor characteristics regarding their importance to detect malignancies. With reference to MRI, radiologists estimated the true positives and negatives of PAM using the variable interval method. An overall probability density function was determined using linear opinion pooling, weighted for individual experts' experience. RESULT: The most important tumor characteristics are mass margins and mass shape. Respondents considered MRI the better technology to visualize these characteristics. Belief elicitation confirmed this by providing an overall sensitivity of PAM ranging from 58.9 to 85.1% (mode 75.6%) and specificity ranging from 52.2 to 77.6% (mode 66.5%). CONCLUSION: Belief elicitation allowed estimates to be obtained for the expected diagnostic performance of PAM, although radiologists expressed difficulties in doing so. Heterogeneity within and between experts reflects this uncertainty and the infancy of PAM. Further clinical trials are required to validate the extent to which this belief-elicitation method is predictive for observed test performance.

Cost-utility of metal-on-metal hip resurfacing compared to conventional total hip replacement in young active patients with osteoarthritis.

BACKGROUND: Metal-on-metal hip resurfacing arthroplasty (MoM HRA) has emerged as an alternative to total hip arthroplasty (THA) for younger active patients with osteoarthritis (OA). Birmingham hip resurfacing is the most common MoM HRA in Alberta, and is therefore compared with conventional THA. OBJECTIVE: The objective of this study was to estimate the expected cost-utility of MoM HRA versus THA, in younger patients with OA, using a decision analytic model with a 15-year time horizon. METHODS: A probabilistic Markov decision analytic model was constructed to estimate the expected cost per quality-adjusted life-year (QALY) of MoM HRA versus THA from a health care payer perspective. The base case considered patients with OA aged 50 years; men comprised 65.9% of the cohort. Sensitivity analyses evaluated cohort age, utility values, failure probabilities, and treatment costs. Data were derived from the Hip Improvement Project and the Hip and Knee Replacement Pilot databases in Alberta, the 2010 National Joint Replacement Registry of the Australian Orthopaedic Association, and the literature. RESULTS: In the base case, THA was dominated by MoM HRA (incremental mean costs of -$583 and incremental mean QALYs of 0.079). In subgroup analyses, THA remained dominated when cohort age was 40 years instead of 50 years or when only men were assessed. THA dominated when the cohort age was 60 years or when only women were assessed. Results were sensitive to utilities, surgery costs, and MoM HRA revision and conversion probabilities. At a willingness-to-pay of Can $50,000/QALY, there was a 58% probability that MoM HRA is cost-effective. CONCLUSIONS: The results show that, on average, MoM HRA was preferred to THA for younger and male patients, but THA is still a reasonable option if the patient or clinician prefers given the small absolute differences between the options and the confidence ellipses around the cost-effectiveness estimates.