Impact of including productivity costs in economic analyses of vaccines for C. difficile infections and infant respiratory syncytial virus, in a UK setting.

OBJECTIVES: It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated. METHODS: For two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results. RESULTS: In this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person. CONCLUSIONS: Considering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

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.

Procalcitonin Biomarker Algorithm Reduces Antibiotic Prescriptions, Duration of Therapy, and Costs in Chronic Obstructive Pulmonary Disease: A Comparison in the Netherlands, Germany, and the United Kingdom.

Antibiotics are often recommended as treatment for patients with chronic obstructive pulmonary disease (COPD) exacerbations. However, not all COPD exacerbations are caused by bacterial infections and there is consequently considerable misuse and overuse of antibiotics among patients with COPD. This poses a severe burden on healthcare resources such as increased risk of developing antibiotic resistance. The biomarker procalcitonin (PCT) displays specificity to distinguish bacterial inflammations from nonbacterial inflammations and may therefore help to rationalize antibiotic prescriptions. We report in this study, a three-country comparison of the health and economic consequences of a PCT biomarker-guided prescription and clinical decision-making strategy compared to current practice in hospitalized patients with COPD exacerbations. A decision tree was developed, comparing the expected costs and effects of the PCT algorithm to current practice in the Netherlands, Germany, and the United Kingdom. The time horizon of the model captured the length of hospital stay and a societal perspective was also adopted. The primary health outcome was the duration of antibiotic therapy. The incremental cost-effectiveness ratio was defined as the incremental costs per antibiotic day avoided. The incremental cost savings per day on antibiotic therapy avoided were (in Euros) €90 in the Netherlands, €125 in Germany, and €52 in the United Kingdom. Probabilistic sensitivity analyses showed that in the majority of simulations, the PCT biomarker strategy was superior to current practice (the Netherlands: 58%, Germany: 58%, and the United Kingdom: 57%). In conclusion, the PCT biomarker algorithm to optimize antibiotic prescriptions in COPD is likely to be cost-effective compared to current practice. Both the percentage of patients who start with antibiotic treatment as well as the duration of antibiotic therapy are reduced with the PCT decision algorithm, leading to a decrease in total costs per patient. Economic analysis based on real-life data is recommended for further research. Biomarker-driven prescription algorithms are important instruments for personalized medicine in COPD. This also attests to the emerging convergence of biomarker innovations and the broader field of Health Technology Assessment (HTA).

(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.

Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine.

Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved "upstream" so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage "upstream" HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers.

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 Systematic Review of Health Economic Evaluations of Diagnostic Biomarkers.

BACKGROUND: Diagnostic biomarkers have multiple applications along the care process and have a large potential in optimizing treatment decisions. However, many diagnostic biomarkers struggle to gain market access and obtain appropriate coverage because of a lack of evidence on their health economic impact. OBJECTIVES: The aim was to review the (methodological) characteristics of recent economic evaluations on diagnostic biomarkers and examine whether these studies dealt with specific issues such as different payer perspectives, preference heterogeneity, and multiple applications in subpopulations. METHODS: The PubMed database and the National Health Service Economic Evaluation Database were searched. Full economic evaluations published after 2009 assessing diagnostic biomarkers for the main non-communicable diseases in middle-income or high-income countries were considered eligible. Empirical and methodological study characteristics were summarized, as was the handling of specific issues related to the economic evaluation of personalized medicine. RESULTS: Thirty-three economic evaluations were included, of which 25 were model-based analyses. The number of strategies compared ranged from two to 17 per study, and was especially large in studies assessing genetic testing in patients and their relatives. Cost-effectiveness results were most sensitive to test accuracy and costs of the biomarker (N = 7), the relative risk of an event (N = 4), and the proportion of people accepting genetic testing (N = 2). One study incorporated patient preferences, and none of the studies considered different payer perspectives, cost sharing arrangements or variable opportunity costs due to population density variability. CONCLUSIONS: Published health economic evaluations of biomarkers used for diagnosing, staging diseases, and guiding treatment selection are characterized by a large number of comparators to model the potential clinical applications and to determine their value. Assessing outcomes beyond health as well as specific issues, such as different payer perspectives and patient preferences, is crucial to fully capture the potential health economic impact of diagnostic biomarkers and to inform value-based reimbursement.

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.

An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics".

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.