Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

Proposal for a General Outcome-based Value Attribution Framework for Combination Therapies.

OBJECTIVE: Valuing and pricing the components of combination therapies can be difficult due to competition law issues, difficulty implementing different prices for the same product in alternative uses, and attributing value to each component of the combination. We propose a value attribution solution that allows all combination components to be priced according to their relative value in the combination. METHODS: We developed a value attribution solution that is universal, symmetrical, and neutral to each combination constituent, regardless of whether it is the backbone or the add-on; and complete, meaning it will always attribute the full value of the combination between the component parts. Moreover, it can be applied to any number of components in the combination (e.g. triplets or quadruplets). We compared this solution to two other existing approaches. RESULTS: The results of the proposed value attribution solution sit between those of the two other value attribution approaches as it combines elements of each. As the degree of additivity moves further away from one in either direction, then our general approach ratios also move, reflecting the impact of the incremental value. CONCLUSION: The proposed value attribution solution for combination therapies differs from two existing approaches by being universally applicable and allowing for symmetry when neutral to the constituent components of the combination. To optimally contribute to policy debate and practice, various requirements for its implementation need to be well understood including how to overcome (1) partial information, (2) whether its assumptions can be relaxed, and (3) implementation issues.

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.

The Value of Vaccines in Maintaining Health System Capacity in England.

OBJECTIVES: In situations of excess demand for healthcare, treating one patient means losing the opportunity to treat another. Therefore, each decision bears an opportunity cost. Nevertheless, when assessing the value of health technologies, these opportunity costs are not always fully considered. We present a pragmatic approach for conceptualizing vaccines' health system capacity value when considering opportunity costs. METHODS: Our approach proxies opportunity costs through the net monetary benefit forgone as scarce healthcare resources are used to treat a vaccine-preventable disease instead of a patient from the waiting list. We apply this approach to cost the resource "hospital beds" for 3 different scenarios of excess demand. Empirically, we estimate the opportunity costs saved for 4 selected vaccination programs from the national schedule in England during a hypothetical scenario of long-lasting excess demand induced by the pandemic. RESULTS: The opportunity cost avoided through vaccination rises with excess demand for treatment. When treating an acute vaccine-preventable outcome is a suboptimal choice compared with treating elective patients, preventing a vaccine-preventable disease from blocking a hospital bed generates opportunity cost savings of approximately twice the direct costs saved by avoiding vaccine-preventable hospitalizations. CONCLUSIONS: Policy makers should be aware that, in addition to preventing the outcome of interest, vaccines and other preventative health technologies deliver value in maintaining regular healthcare services and clearing the pent-up demand from the pandemic. Therefore, health system capacity value should be a key-value element in health technology assessment. Existing and potential future vaccination programs deliver more value than hitherto quantified.

Recognizing the Broader Value of Meningococcal Vaccination: A Matter of Evidence, Ability, or Willingness?

OBJECTIVES: It is widely argued that the value of meningococcal vaccination extends beyond the narrow value elements traditionally considered in health technology assessment. Nevertheless, measuring broader value presents challenges, whereas assessment methods and outcomes vary widely. This article investigates the extent to which the broader value of meningococcal vaccination is recognized, considering the available evidence and decision maker's methodological ability and willingness. METHODS: A targeted literature review informed the classification of broader value elements according to their relevance to meningococcal vaccination and the quality of existing evidence. Focusing on relevant value elements with good evidentiary standards, decision makers' perspectives and methodological ability to consider them were assessed through case studies of health technology assessment of meningococcal B vaccination in England and The Netherlands. RESULTS: Value elements of high relevance to meningococcal vaccination with good quality evidence include caregivers' health gains, patients' lifetime productivity gains, and disease severity. The willingness and methodological ability to incorporate them into value assessments have been mixed. This is attributable to the scope of the value assessment perspective and the use of evaluation methods that do not fully capture broader value. For other broader value elements, evidence gaps are another potential barrier to value demonstration and recognition. CONCLUSIONS: The current evidence base confirms that the value of meningococcal vaccination spans beyond healthcare sector effects to health-related externalities, allocative value, and societal economic benefits. To ensure that the most efficient resource allocation outcomes are achieved, countries should consider how to improve their perspective and methodological ability to assess broader value elements accurately.

Why We Need a New Outcomes-Based Value Attribution Framework for Combination Regimens in Oncology.

BACKGROUND: Novel oncology treatment strategies increasingly use medicines with distinct but complementary mechanisms of action in combination or in close sequence. Payers, when confronted with higher total cost of providing combination regimens involving multiple therapies and usually longer treatment durations, are reluctant to reimburse them, particularly when they perceive the expected incremental benefits from adding a new medicine (the add-on) to a currently reimbursed medicine (the backbone) not to represent value for money to the health system. Nevertheless, depending on how value is attributed to the add-on versus the backbone, a clinically effective medicine used as part of a regimen that increases treatment duration might be found "not cost-effective at zero price." This phenomenon, signaling a policy problem not a pricing issue, first needs to be better understood before a generalizable and transparent solution can be presented. OBJECTIVE: This article sets out when this policy challenge arises and describes general principles that any proposed solution to the value attribution problem must satisfy. METHODS: We develop a simplified conceptual framework and use this to address 2 topics. The first is to understand the origin of problems posed by the current approach for attributing value in incremental cost-effectiveness analyses of combination regimens. The second is to discuss 2 new approaches in the literature designed to address the challenge. FINDINGS: We find that neither meets our criteria, meaning that further work is needed to resolve the issue. Finally, we briefly discuss the implications of relaxing the simplifying assumptions in our conceptual framework.

Value of Information Analytical Methods: Report 2 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

The allocation of healthcare resources among competing priorities requires an assessment of the expected costs and health effects of investing resources in the activities and of the opportunity cost of the expenditure. To date, much effort has been devoted to assessing the expected costs and health effects, but there remains an important need to also reflect the consequences of uncertainty in resource allocation decisions and the value of further research to reduce uncertainty. Decision making with uncertainty may turn out to be suboptimal, resulting in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to better inform resource decisions. This value can be quantified using value of information (VOI) analysis. This report from the ISPOR VOI Task Force describes methods for computing 4 VOI measures: the expected value of perfect information, expected value of partial perfect information (EVPPI), expected value of sample information (EVSI), and expected net benefit of sampling (ENBS). Several methods exist for computing EVPPI and EVSI, and this report provides guidance on selecting the most appropriate method based on the features of the decision problem. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing VOI analyses. The software needed to compute VOI is discussed, and areas for future research are highlighted.

Value of Information Analysis for Research Decisions-An Introduction: Report 1 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force.

Healthcare resource allocation decisions made under conditions of uncertainty may turn out to be suboptimal. In a resource constrained system in which there is a fixed budget, these suboptimal decisions will result in health loss. Consequently, there may be value in reducing uncertainty, through the collection of new evidence, to make better resource allocation decisions. This value can be quantified using a value of information (VOI) analysis. This report, from the ISPOR VOI Task Force, introduces VOI analysis, defines key concepts and terminology, and outlines the role of VOI for supporting decision making, including the steps involved in undertaking and interpreting VOI analyses. The report is specifically aimed at those tasked with making decisions about the adoption of healthcare or the funding of healthcare research. The report provides a number of recommendations for good practice when planning, undertaking, or reviewing the results of VOI analyses.

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.

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.

Surveillance magnetic resonance imaging for isolated optic pathway gliomas: is gadolinium necessary?

BACKGROUND: Pediatric optic pathway gliomas are typically indolent but have a variable clinical course. Treatment is dictated by symptoms and changes on contrast-enhanced MRI examinations. Gadolinium retention in children has motivated parsimonious use of gadolinium-based contrast agents. OBJECTIVES: To determine surveillance MR factors that motivate changes in tumor-directed therapies and extrapolate cost-efficacy of a non-contrast follow-up protocol. MATERIALS AND METHODS: Using an imaging database search we identified children with isolated optic pathway gliomas and ≥3 follow-up contrast-enhanced MRIs. We reviewed medical records and imaging for: (1) coincident changes on contrast-enhanced MRI and tumor-directed therapy, (2) demographics and duration of follow-up, (3) motivations for intervention, (4) assessment of gadolinium-based contrast agents' utility and (5) health care utilization data. We assessed cost impact in terms of relative value unit (RVU) burden. RESULTS: We included 17 neurofibromatosis type 1 (NF1) and 21 non-NF1 patients who underwent a median 16.9 and 24.3 cumulative contrast-enhanced MR exams over 7.7 years and 8.1 years of follow-up, respectively. Eight children (one with NF1) had intervention based on contrast-enhanced MR findings alone. For these eight, increased tumor size was the only common feature, and it was apparent on non-contrast T2 sequences. For the median patient, a non-contrast follow-up protocol could result in 15.9 (NF1) and 23.3 (non-NF1) fewer gadolinium-based contrast agent administrations, and a 39% lower yearly RVU burden. CONCLUSION: Pediatric patients with isolated optic pathway gliomas undergo a large number of routine contrast-enhanced MR follow-up exams. Gadolinium might not be needed for these exams to inform management decisions. Secondary benefits of a non-contrast follow-up protocol include decreased cost and risk to the patient.

Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

Uncertainty of Physicians and Patients in Medical Decision Making.

Modern medicine has developed an apparently unlimited array of diagnostic and therapeutic tools; for example, treatment options for patients with hematologic malignancies are expanding rapidly. These developments, offering a spectrum of modalities, provide a new outlook on successful treatment for many patients. Nontheless, decisions regarding the optimum treatment strategy for any individual patient remain challenging, given that all prognostic projections are based on statistics. The challenge lies in identifying parameters that characterize individual patients as prospective responders or nonresponders and thus determine the prognosis. Both physicians and patients are confronted with the uncertainty of the success of treatment with any strategy in a particular disease condition and with the impact of treatment on overall prognosis. How certain can a physician be that an individual patient has the best prognosis with a particular intervention? How does a physician's own uncertainty affect decisions made by a less-informed patient? Here we examine various aspects of uncertainty and their relevance in the process of medical decision making as briefly illustrated by 2 clinical scenarios of hematologic malignancies.

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.

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.

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.

Development of a web-based tool for the assessment of health and economic outcomes of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA).

BACKGROUND: The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) is a European Commission led policy initiative to address the challenges of demographic change in Europe. For monitoring the health and economic impact of the social and technological innovations carried out by more than 500 stakeholder's groups ('commitments') participating in the EIP on AHA, a generic and flexible web-based monitoring and assessment tool is currently being developed. AIM: This paper describes the approach for developing and implementing this web-based tool, its main characteristics and capability to provide specific outcomes that are of value to the developers of an intervention, as well as a series of case studies planned before wider rollout. METHODS: The tool builds up from a variety of surrogate endpoints commonly used across the diverse set of EIP on AHA commitments in order to estimate health and economic outcomes in terms of incremental changes in quality adjusted life years (QALYs) as well as health and social care utilisation. A highly adaptable Markov model with initially three mutually exclusive health states ('baseline health', 'deteriorated health' and 'death') provides the basis for the tool which draws from an extensive database of epidemiological, economic and effectiveness data; and also allows further customisation through remote data entry enabling more accurate and context specific estimation of intervention impact. Both probabilistic sensitivity analysis and deterministic scenario analysis allow assessing the impact of parameter uncertainty on intervention outcomes. A set of case studies, ranging from the pre-market assessment of early healthcare technologies to the retrospective analysis of established care pathways, will be carried out before public rollout, which is envisaged end 2015. CONCLUSION: Monitoring the activities carried out within the EIP on AHA requires an approach that is both flexible and consistent in the way health and economic impact is estimated across interventions and commitments. The added value for users of the MAFEIP-tool is its ability to provide an early assessment of the likelihood that interventions in their current design will achieve the anticipated impact, and also to identify what drives interventions' effectiveness or efficiency to guide further design, development or evaluation.