Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial.

INTRODUCTION: In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC-IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis. METHODS: A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed. RESULTS: Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most. CONCLUSION: Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC-IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.

Early Cost-Effectiveness Analysis of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Patients with Limited Peritoneal Carcinomatosis.

BACKGROUND: Gastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting. METHODS: We constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases. RESULTS: In the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model. CONCLUSIONS: The presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

High-dose chemotherapy with stem cell rescue to treat stage III homologous deficient breast cancer: factors influencing clinical implementation.

BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDCT) is a promising treatment for patients with stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer. Clinical effectiveness and cost-effectiveness are currently under investigation in an international multicenter randomized controlled trial. To increase the chance of successful introduction of HDCT into daily clinical practice, we aimed to identify relevant factors for smooth implementation using an early comprehensive assessment framework. METHODS: This is a qualitative, multi-stakeholder, exploratory research using semi-structured interviews guided by the Constructive Technology Assessment model, which evaluates the quality of a novel health technology by clinical, economic, patient-related, and organizational factors. Stakeholders were recruited by purposeful stratified sampling and interviewed until sufficient content saturation was reached. Two researchers independently created themes, categories, and subcategories by following inductive coding steps, these were verified by a third researcher. RESULTS: We interviewed 28 stakeholders between June 2019 and April 2021. In total, five overarching themes and seventeen categories were identified. Important findings for optimal implementation included the structural identification and referral of all eligible patients, early integration of supportive care, multidisciplinary collaboration between- and within hospitals, (de)centralization of treatment aspects, the provision of information for patients and healthcare professionals, and compliance to new regulation for the BRCA1-like test. CONCLUSIONS: In anticipation of a positive reimbursement decision, we recommend to take the highlighted implementation factors into consideration. This might expedite and guide high-quality equitable access to HDCT for patients with stage III, HER2-negative, HRD breast cancer in the Netherlands.

Cost-Effectiveness and Budget Impact of Future Developments With Whole-Genome Sequencing for Patients With Lung Cancer.

OBJECTIVES: This study aimed to investigate the cost-effectiveness, budget impact (BI), and impact of uncertainty of future developments concerning whole-genome sequencing (WGS) as a clinical diagnostic test compared with standard of care (SoC) in patients with locally advanced and metastatic non-small cell lung cancer. METHODS: A total of 3 likely scenarios to take place within 5 years (according to experts) were simulated using a previously developed, peer reviewed, and published decision model. The scenarios concerned "WGS results used for treatment selection" (scenario 1), "WGS-based biomarker for immunotherapy" (scenario 2), and "off-label drug approval for WGS results" (scenario 3). Two diagnostic strategies of the original model, "SoC" and "WGS as a diagnostic test" (base model), were used to compare our scenarios with. Outcomes were reported for the base model, all scenarios separately, combined (combined unweighted), and weighted by likelihood (combined weighted). Cost-effectiveness, BI, and value of information analyses were performed for WGS compared with SoC. RESULTS: Total costs and quality-adjusted life-years for SoC in metastatic non-small cell lung cancer were €149 698 and 1.235. Incremental outcomes of WGS were €1529/0.002(base model), -€222/0.020(scenario 1), -€2576/0.023(scenario 2), €388/0.024(scenario 3), -€5041/0.060(combined unweighted), and -€1715/0.029(combined weighted). The annual BI for adopting WGS for this population in The Netherlands ranged between €682 million (combined unweighted) and €714 million (base model). The consequences of uncertainty amounted to €3.4 million for all scenarios (combined weighted) and to €699 000 for the diagnostic yield of WGS alone (combined weighted). CONCLUSIONS: Our findings suggest that it is likely for WGS to become cost-effective within the near future if it identifies more patients with actionable targets and show the impact of uncertainty regarding its diagnostic yield. Modeling future scenarios can be useful to consider early adoption of WGS while timely anticipating on unforeseen developments before final conclusions are reached.

Budget impact analysis of providing hospital inpatient care at home virtually, starting with two specific surgical patient groups.

OBJECTIVE: To determine the budget impact of virtual care. METHODS: We conducted a budget impact analysis of virtual care from the perspective of a large teaching hospital in the Netherlands. Virtual care included remote monitoring of vital signs and three daily remote contacts. Net budget impact over 5 years and net costs per patient per day (costs/patient/day) were calculated for different scenarios: implementation in one ward, in two different wards, in the entire hospital, and in multiple hospitals. Sensitivity analyses included best-case and worst-case scenarios, and reducing the frequency of daily remote contacts. RESULTS: Net budget impact over 5 years was €2 090 000 for implementation in one ward, €410 000 for two wards and €-6 206 000 for the entire hospital. Costs/patient/day in the first year were €303 for implementation in one ward, €94 for two wards and €11 for the entire hospital, decreasing in subsequent years to a mean of €259 (SD=€72), €17 (SD=€10) and €-55 (SD=€44), respectively. Projecting implementation in every Dutch hospital resulted in a net budget impact over 5 years of €-445 698 500. For this scenario, costs/patient/day decreased to €-37 in the first year, and to €54 in subsequent years in the base case. CONCLUSIONS: With present cost levels, virtual care only saves money if it is deployed at sufficient scale or if it can be designed such that the active involvement of health professionals is minimised. Taking a greenfield approach, involving larger numbers of hospitals, further decreases costs compared with implementing virtual care in one hospital alone.

Cost-utility analysis on robot-assisted and laparoscopic prostatectomy based on long-term functional outcomes.

Robot-Assisted Radical Prostatectomy (RARP) is one of the standard treatment options for prostate cancer. However, controversy still exists on its added value. Based on a recent large-sample retrospective cluster study from the Netherlands showing significantly improved long-term urinary functioning after RARP compared to Laparoscopic RP (LRP), we evaluated the cost-effectiveness of RARP compared to LRP. A decision tree was constructed to measure the costs and effects from a Dutch societal perspective over a ~ 7 year time-horizon. The input was based on the aforementioned study, including patient-reported consumption of addition care and consumed care for ergonomic issues reported by surgeons. Intervention costs were calculated using a bottom-up costing analysis in 5 hospitals. Finally, a probabilistic-, one-way sensitivity- and scenario analyses were performed to show possible decision uncertainty. The intervention costs were €9964 for RARP and €7253 for LRP. Total trajectory costs were €12,078 for RARP and €10,049 for LRP. RARP showed higher QALYs compared to LRP (6.17 vs 6.11). The incremental cost-utility ratio (ICUR) was €34,206 per QALY gained, in favour of RARP. As a best-case scenario, when RARP is being centralized (> 150 cases/year), total trajectory costs decreased to €10,377 having a higher utilization, and a shorter procedure time and length of stay resulting in an ICUR of €3495 per QALY gained. RARP showed to be cost-effective compared to LRP based on data from a population-based, large scale study with 7 years of follow-up. This is a clear incentive to fully reimburse RARP, especially when hospitals provide RARP centralized.

Image-guided navigation for locally advanced primary and locally recurrent rectal cancer: evaluation of its early cost-effectiveness.

BACKGROUND: A first pilot study showed that an image-guided navigation system could improve resection margin rates in locally advanced (LARC) and locally recurrent rectal cancer (LRRC) patients. Incremental surgical innovation is often implemented without reimbursement consequences, health economic aspects should however also be taken into account. This study evaluates the early cost-effectiveness of navigated surgery compared to standard surgery in LARC and LRRC. METHODS: A Markov decision model was constructed to estimate the expected costs and outcomes for navigated and standard surgery. The input parameters were based on pilot data from a prospective (navigation cohort n = 33) and retrospective (control group n = 142) data. Utility values were measured in a comparable group (n = 63) through the EQ5D-5L. Additionally, sensitivity and value of information analyses were performed. RESULTS: Based on this early evaluation, navigated surgery showed incremental costs of €3141 and €2896 in LARC and LRRC. In LARC, navigated surgery resulted in 2.05 Quality-Adjusted Life Years (QALYs) vs 2.02 QALYs for standard surgery. For LRRC, we found 1.73 vs 1.67 QALYs respectively. This showed an Incremental Cost-Effectiveness Ratio (ICER) of €136.604 for LARC and €52.510 for LRRC per QALY gained. In scenario analyses, optimal utilization rates of the navigation technology lowered the ICER to €61.817 and €21.334 for LARC and LRRC. The ICERs of both indications were most sensitive to uncertainty surrounding the risk of progression in the first year after surgery, the risk of having a positive surgical margin, and the costs of the navigation system. CONCLUSION: Adding navigation system use is expected to be cost-effective in LRRC and has the potential to become cost-effective in LARC. To increase the probability of being cost-effective, it is crucial to optimize efficient use of both the hybrid OR and the navigation system and identify subgroups where navigation is expected to show higher effectiveness.

Cell-Free DNA at Diagnosis for Stage IV Non-Small Cell Lung Cancer: Costs, Time to Diagnosis and Clinical Relevance.

Tissue biopsies can be burdensome and are only effective in 10-30% of patients with metastasized non-small-cell lung cancer (mNSCLC). Next-generation sequencing (NGS) on cell-free DNA (cfDNA) might be an attractive alternative. We evaluated the costs, throughput time, and diagnostic yield of two diagnostic scenarios with tissue and cfDNA for mNSCLC patients, compared to diagnostics based on tissue biopsy alone. Data were retrieved from 209 stage IV NSCLC patients included in 10 hospitals in the Netherlands in the observational Lung cancer Early Molecular Assessment (LEMA) trial. Discrete event simulation was developed to compare three scenarios, using LEMA data as input where possible: (1) diagnostics with "tissue only"; (2) diagnostics with "cfDNA first", and subsequent tissue biopsy if required (negative for EGFR, BRAF ALK, ROS1); (3) cfDNA if tissue biopsy failed ("tissue first"). Scenario- and probabilistic analyses were performed to quantify uncertainty. In scenario 1, 84% (Credibility Interval [CrI] 70-94%) of the cases had a clinically relevant test result, compared to 93% (CrI 86-98%) in scenario 2, and 93% (CrI 86-99%) in scenario 3. The mean throughput time was 20 days (CrI 17-23) pp in scenario 1, 9 days (CrI 7-11) in scenario 2, and 19 days (CrI 16-22) in scenario 3. Mean costs were €2304 pp (CrI €2067-2507) in scenario 1, compared to €3218 (CrI €3071-3396) for scenario 2, and €2448 (CrI €2382-2506) for scenario 3. Scenarios 2 and 3 led to a reduction in tissue biopsies of 16% and 9%, respectively. In this process-based simulation analysis, the implementation of cfDNA for patients with mNSCLC resulted in faster completion of molecular profiling with more identified targets, with marginal extra costs in scenario 3.

Developing a dynamic simulation model to support the nationwide implementation of whole genome sequencing in lung cancer.

BACKGROUND: This study shows how dynamic simulation modeling can be applied in the context of the nationwide implementation of Whole Genome Sequencing (WGS) for non-small cell lung cancer (NSCLC) to inform organizational decisions regarding the use of complex and disruptive health technologies and how these decisions affect their potential value. METHODS: Using the case of the nationwide implementation of WGS into clinical practice in lung cancer in the Dutch healthcare system, we developed a simulation model to show that including service delivery features across the diagnostic pathway can provide essential insight into the affordability and accessibility of care at the systems level. The model was implemented as a hybrid Agent-Based Model and Discrete-Event Simulation model in AnyLogic and included 78 hospital agents, 7 molecular tumor board agents, 1 WGS facility agent, and 5313 patient agents each year in simulation time. RESULTS: The model included patient and provider heterogeneity, including referral patterns, capacity constraints, and diagnostic workflows. Patient preference and adoption by healthcare professionals were also modeled. The model was used to analyze a scenario in which only academic hospitals have implemented WGS. To prevent delays in the diagnostic pathway, the capacity to sequence at least 1600 biopsies yearly should be present. There is a two-fold increase in mean diagnostic pathway duration between no patients referred or all patients referred for further diagnostics. CONCLUSIONS: The systems model can complement conventional health economic evaluations to investigate how the organization of the workflow can influence the actual use and impact of WGS. Insufficient capacity to provide WGS and referral patterns can substantially impact the duration of the diagnostic pathway and thus should be considered in the implementation of WGS.

Improving the Affordability of Anticancer Medicines Demands Evidence-Based Policy Solutions.

The high cost of many new anticancer medicines significantly impedes breakthrough discoveries from reaching patients. A commonly heard refrain is that high prices are necessary to compensate for the high costs of research and development (R&D). Yet, there are promising policy proposals aimed at improving affordability without compromising innovation. In seeking new policy solutions, we argue for a shift away from entrenched opinion toward an evidence-based discourse that is grounded in experiments and real-world pilot studies. We offer a novel perspective and practical recommendations on how empirical evidence could and should be gathered to inform evidence-based policy interventions that lead to sustainable medicine prices in oncology.See related article by Franzen et al. (Cancer Res Commun 2022;2:39-47).

Affordable Prices Without Threatening the Oncological R&D Pipeline-An Economic Experiment on Transparency in Price Negotiations.

The high prices of innovative medicines endanger access to care worldwide. Sustainable prices need to be affordable while sufficiently incentivizing research and development (R&D) investments. A proposed solution is increased transparency. Proponents argue that price and R&D cost confidentiality are drivers of high prices. On the contrary, supporters of confidentiality claim that confidentiality enables targeted discounts which make treatments affordable; moreover, pharmaceutical companies argue that R&D investments would suffer with more transparency. Despite the political relevance, limited empirical evidence exists on the effects of transparency regulations. We contribute to fill this gap with an experiment where we replicate the EU pharmaceutical market in a laboratory setting. In a randomized controlled study, we analyzed how participants, 400 students located in four European countries, negotiated in the current system of Price Secrecy in comparison with innovative bargaining settings where either prices only (Price Transparency) or prices and R&D costs (Full Transparency) were made transparent to buyers. We found that Price transparency had no statistically significant effect on average prices or number of patients treated and made R&D investments significantly smaller (-16.86%; P: 0.0024). On the other hand, Full Transparency reduced prices (-26%; P: 0.0004) and held the number of patients constant at the level of Price Secrecy. It produced price convergence between countries with low and high health budgets, and, despite lower prices, had no effect on R&D investments. Our findings provide novel evidence that combining price and R&D cost transparency could be an effective policy to contribute to sustainable medicine prices. See related article by Franzen et al. (Cancer Discov 2022;12:299-302).

Understanding the Costs of Surgery: A Bottom-Up Cost Analysis of Both a Hybrid Operating Room and Conventional Operating Room.

BACKGROUND: Over the past decade, many hospitals have adopted hybrid operating rooms (ORs). As resources are limited, these ORs have to prove themselves in adding value. Current estimations on standard OR costs show great variety, while cost analyses of hybrid ORs are lacking. Therefore, this study aims to identify the cost drivers of a conventional and hybrid OR and take a first step in evaluating the added value of the hybrid OR. METHODS: A comprehensive bottom-up cost analysis was conducted in five Dutch hospitals taking into account: construction, inventory, personnel and overhead costs by means of interviews and hospital specific data. The costs per minute for both ORs were calculated using the utilization rates of the ORs. Cost drivers were identified by sensitivity analyses. RESULTS: The costs per minute for the conventional OR and the hybrid OR were €9.45 (€8.60-€10.23) and €19.88 (€16.10- €23.07), respectively. Total personnel and total inventory costs had most impact on the conventional OR costs. For the hybrid OR the costs were mostly driven by utilization rate, total inventory and construction costs. The results were incorporated in an open access calculation model to enable adjustment of the input parameters to a specific hospital or country setting. CONCLUSION: This study estimated a cost of €9.45 (€8.60-€10.23) and €19.88 (€16.10-€23.07) for the conventional and hybrid OR, respectively. The main factors influencing the OR costs are: total inventory costs, total construction costs, utilization rate, and total personnel costs. Our analysis can be used as a basis for future research focusing on evaluating value for money of this promising innovative OR. Furthermore, our results can inform surgeons, and decision and policy-makers in hospitals on the adoption and optimal utilization of new (hybrid) ORs.

Early Cost Effectiveness of Whole-Genome Sequencing as a Clinical Diagnostic Test for Patients with Inoperable Stage IIIB,C/IV Non-squamous Non-small-Cell Lung Cancer.

BACKGROUND: Advanced non-small-cell lung cancer (NSCLC) harbours many genetic aberrations that can be targeted with systemic treatments. Whole-genome sequencing (WGS) can simultaneously detect these (and possibly new) molecular targets. However, the exact added clinical value of WGS is unknown. OBJECTIVE: The objective of this study was to determine the early cost effectiveness of using WGS in diagnostic strategies compared with currently used molecular diagnostics for patients with inoperable stage IIIB,C/IV non-squamous NSCLC from a Dutch healthcare perspective. METHODS: A decision tree represented the diagnostic pathway, and a cohort state transition model represented disease progression. Three diagnostic strategies were modelled: standard of care (SoC) alone, WGS as a diagnostic test, and SoC followed by WGS. Treatment effectiveness was based on a systematic review. Probabilistic cost-effectiveness analyses were performed, and threshold analyses (using €80,000 per quality-adjusted life-year [QALY]) was used to explore the early cost effectiveness of WGS. RESULTS: WGS as a diagnostic test resulted in more QALYs (0.002) and costs (€1534 [incremental net monetary benefit -€1349]), and SoC followed by WGS resulted in fewer QALYs (-0.002) and more costs (€1059 [-€1194]) compared with SoC alone. WGS as a diagnostic test was only cost effective if it was priced at €2000 per patient and identified 2.7% more actionable patients than SoC alone. Treating these additional identified patients with new treatments costing >€4069 per month decreased the probability of cost effectiveness. CONCLUSIONS: Our analysis suggests that providing WGS as a diagnostic test is cost effective compared with SoC followed by WGS and SoC alone if costs for WGS decrease and additional patients with actionable targets are identified. This cost-effectiveness model can be used to incorporate new findings iteratively and to support ongoing decision making regarding the use of WGS in this rapidly evolving field.

Whole genome sequencing in oncology: using scenario drafting to explore future developments.

BACKGROUND: In oncology, Whole Genome Sequencing (WGS) is not yet widely implemented due to uncertainties such as the required infrastructure and expertise, costs and reimbursements, and unknown pan-cancer clinical utility. Therefore, this study aimed to investigate possible future developments facilitating or impeding the use of WGS as a molecular diagnostic in oncology through scenario drafting. METHODS: A four-step process was adopted for scenario drafting. First, the literature was searched for barriers and facilitators related to the implementation of WGS. Second, they were prioritized by international experts, and third, combined into coherent scenarios. Fourth, the scenarios were implemented in an online survey and their likelihood of taking place within 5 years was elicited from another group of experts. Based on the minimum, maximum, and most likely (mode) parameters, individual Program Evaluation and Review Technique (PERT) probability density functions were determined. Subsequently, individual opinions were aggregated by performing unweighted linear pooling, from which summary statistics were extracted and reported. RESULTS: Sixty-two unique barriers and facilitators were extracted from 70 articles. Price, clinical utility, and turnaround time of WGS were ranked as the most important aspects. Nine scenarios were developed and scored on likelihood by 18 experts. The scenario about introducing WGS as a clinical diagnostic with a lower price, shorter turnaround time, and improved degree of actionability, scored the highest likelihood (median: 68.3%). Scenarios with low likelihoods and strong consensus were about better treatment responses to more actionable targets (26.1%), and the effect of centralizing WGS (24.1%). CONCLUSIONS: Based on current expert opinions, the implementation of WGS as a clinical diagnostic in oncology is heavily dependent on the price, clinical utility (both in terms of identifying actionable targets as in adding sufficient value in subsequent treatment), and turnaround time. These aspects and the optimal way of service provision are the main drivers for the implementation of WGS and should be focused on in further research. More knowledge regarding these factors is needed to inform strategic decision making regarding the implementation of WGS, which warrants support from all relevant stakeholders.

Early technology assessment of using whole genome sequencing in personalized oncology.

Introduction: Personalized medicine-based treatments in advanced cancer hold the promise to offer substantial health benefits to genetic subgroups, but require efficient biomarker-based patient stratification to match the right treatment and may be expensive. Standard molecular diagnostics are currently very heterogeneous, and tests are often performed sequentially. The alternative to whole genome sequencing (WGS) i.e. simultaneously testing for all relevant DNA-based biomarkers thereby allowing immediate selection of the most optimal therapy, is more costly than current techniques. In the current implementation stage, it is important to explore the added value and cost-effectiveness of using WGS on a patient level and to assess optimal introduction of WGS on the level of the healthcare system.Areas covered: First, an overview of current worldwide initiatives concerning the use of WGS in clinical practice for cancer diagnostics is given. Second, a comprehensive, early health technology assessment (HTA) approach of evaluating WGS in the Netherlands is described, relating to the following aspects: diagnostic value, WGS-based treatment decisions, assessment of long-term health benefits and harms, early cost-effectiveness modeling, nation-wide organization, and Ethical, Legal and Societal Implications.Expert opinion: This study provides evidence to guide further development and implementation of WGS in clinical practice and the healthcare system.

Real-World Utilization of Biomarker Testing for Patients with Advanced Non-Small Cell Lung Cancer in a Tertiary Referral Center and Referring Hospitals.

The continued introduction of biomarkers and innovative testing methods makes already complex diagnosis in patients with stage IV non-small-cell lung cancer (NSCLC) even more complex. This study primarily analyzed variations in biomarker testing in clinical practice in patients referred to a comprehensive cancer center in the Netherlands. The secondary aim was to compare the cost of biomarker testing with the cost of whole-genome sequencing. The cohort included 102 stage IV NSCLC patients who received biomarker testing in 2017 or 2018 at the comprehensive cancer center. The complete biomarker testing history of the cohort was identified using linked data from the comprehensive cancer center and the nationwide network and registry of histopathology and cytopathology in the Netherlands. Unique biomarker-test combinations, costs, turnaround times, and test utilization were examined. The results indicate substantial variation in test utilization and sequences. The mean cost per patient of biomarker testing was 2259.92 ± 1217.10 USD, or 1881.23 ± 1013.15 EUR. Targeted gene panels were most frequently conducted, followed by IHC analysis for programmed cell death protein ligand 1. Typically, the most common biomarkers were assessed within the first tests, and emerging biomarkers were tested further down the test sequence. At the cost of current biomarker testing, replacing current testing with whole-genome sequencing would have led to cost-savings in only two patients (2%).

Selecting Image-Guided Surgical Technologies in Oncology: A Surgeon's Perspective.

BACKGROUND: To improve surgical performance, image-guided (IG) technologies are increasingly introduced. Yet, it is unknown which oncological procedures yield most value from these technologies. This study aimed to select the most promising IG technology per oncologic indication. METHODS: An Analytic Hierarchical Process was used to evaluate three IG technologies: navigation, optical imaging, and augmented reality, in five oncologic indications compared with usual care. Sixteen decision criteria were selected. The relative importance of the criteria and the expected performance of the technologies were evaluated among surgeons. The combination of these scores gives the expected value per technology. RESULTS: On criteria level, sparing critical tissue (9%-18%) and reducing the risk of local recurrence (11%-27%) were most important. Navigation was preferred in three indications-removal of lymph nodes (42%), liver (47%), and rectal tumors (33%). In removing rectal tumors, optical imaging was equally preferred (34%). In removing breast and tongue tumors, no technology was clearly preferred. CONCLUSIONS: In selecting IG technologies, especially optical and navigation technologies are expected to add value in addition to usual care. Further development of those technologies for the preferred indications seems valuable. Multi-attribute analysis showed to be useful in prioritization of conducting clinical studies and steer research and development initiatives.

Cost-Effectiveness of Surgery Versus Organ Preservation in Advanced Laryngeal Cancer.

OBJECTIVE: Treatment decision-making for patients with laryngeal cancer consists of a complex trade-off between survival and quality of life. For decision makers on coverage and guidelines, costs come in addition to this equation. Our aim was to perform a cost-effectiveness analysis of surgery (laryngectomy with or without radiotherapy) versus organ preservation (OP: radiotherapy, chemo- and/or bioradiation) in advanced laryngeal cancer patients from a healthcare perspective. METHODS: A cost-effectiveness analysis was conducted using a Markov model. For each modality, data on survival and quality-adjusted life years (QALYs) were sourced from relevant articles in agreement with experts, and national benchmark cost prices were included regarding treatment, follow-up, adverse events, and rehabilitation. RESULTS: Total QALYs of the surgical approach (6.59) were substantially higher compared to the OP approach (5.44). Total lifetime costs were higher for the surgical approach compared to the OP approach, namely €95,881 versus €47,233. The surgical approach was therefore more effective and more costly compared to OP, resulting in an incremental cost-effectiveness ratio of €42,383/QALY. CONCLUSION: Based on current literature, surgical treatment was cost-effective compared to OP in advanced laryngeal cancer within most willingness-to-pay thresholds. The study provides information on the survival adjusted for quality of life in combination with costs of two different approaches for advanced laryngeal cancer, relevant for patients, physicians, and policy makers. As financial toxicity is a relevant aspect in this population, collection of real-world data on country-specific costs and utilities is strongly recommended to enable further generalization. LEVEL OF EVIDENCE: N/A. Laryngoscope, 131:E509-E517, 2021.

Cost-effectiveness analysis of using the heat and moisture exchangers compared with alternative stoma covers in laryngectomy rehabilitation: US perspective.

BACKGROUND: This study aims to evaluate the cost-effectiveness of using heat and moisture exchangers (HMEs) vs alternative stoma covers (ASCs) following laryngectomy in the United States. METHODS: A cost-effectiveness and budget impact analysis were conducted including uncertainty analyses using real-world survey data with pulmonary events and productivity loss. RESULTS: HME use was more effective and less costly compared with ASCs. Quality-adjusted life years were slightly higher for HME-users. Total costs per patient (lifetime) were $59 362 (HME) and $102 416 (ASC). Pulmonary events and productivity loss occurred more frequently in the ASC-users. Annual budget savings were up to $40 183 593. Costs per pulmonary event averted were $3770. CONCLUSIONS: HME utilization in laryngectomy patients was cost-effective. Reimbursement of HME devices is thus recommended. Utilities may be underestimated due to the generic utility instrument used and sample size. Therefore, we recommend development of a disease-specific utility tool to incorporate in future analyses.

Cost-effectiveness analysis of the 70-gene signature compared with clinical assessment in breast cancer based on a randomised controlled trial.

BACKGROUND: The clinical utility of the 70-gene signature (MammaPrint®) to guide chemotherapy use in T1-3N0-1M0 breast cancer was demonstrated in the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) study. One thousand four ninety seven of 3356 (46.2%) enrolled patients with high clinical risk (in accordance with the modified Adjuvant! Online clinical-pathological assessment) had a low-risk 70-gene signature. Using patient-level data from the MINDACT trial, the cost-effectiveness of using the 70-gene signature to guide adjuvant chemotherapy selection for clinical high risk, estrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) patients was analysed. PATIENTS AND METHODS: A hybrid decision tree-Markov model simulated treatment strategies in accordance with the 70-gene signature with clinical assessment versus clinical assessment alone, over a 10-year time horizon. Primary outcomes were quality-adjusted life years (QALYs), country-specific costs and incremental cost-effectiveness ratios (ICERs) for six countries: Belgium, France, Germany, Netherlands, UK and the US. RESULTS: Treatment strategies guided by the 70-gene signature result in more QALYs compared with clinical assessment alone. Costs of the 70-gene signature strategy were lower in five of six countries. This led to dominance of the 70-gene signature in Belgium, France, Germany, Netherlands and the US and to a cost-effective situation in the UK (ICER £22,910/QALY). Annual national cost savings were €4.2M (Belgium), €24.7M (France), €45.1M (Germany), €12.7M (Netherlands) and $244M (US). UK budget increase was £8.4M. CONCLUSION: Using the 70-gene signature to safely guide chemotherapy de-escalation in clinical high risk patients with ER+/HER2- tumours is cost-effective compared with using clinical assessment alone. Long-term follow-up and outcomes from the MINDACT trial are necessary to address uncertainties in model inputs.