Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data.

Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) for advanced solid tumors have typically required models with assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life quality of care. Methods: Cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumors through the OCTANE clinical trial (NCT02906943). This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enrolled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enrolled in OCTANE. Patients were matched according to 19 patient, disease and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main Outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrollment and end-of-life quality metrics. Findings: There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardized difference <0.10). There were higher mean health-care costs with OCTANE ($79,702 vs. $59,550), mainly due to outpatient and specialist visits. Publicly funded drug costs were less with OCTANE ($20,015 vs. $24,465). OCTANE enrollment was not associated with improved OS (restricted mean survival time [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p = 0.153), varying by tumor type. In five tumor types with ≥35 OCTANE patients, OS was similar in three (breast, colon, uterus, all p > 0.40), and greater in two (ovary, biliary, both p < 0.05). OCTANE was associated with greater clinical trial enrollment (25.4% vs. 9.5%, p < 0.001) and better end-of-life quality due to less death in hospital (10.2% vs. 16.4%, p = 0.003). Results were robust in sensitivity analysis. Interpretation: We found an increase in healthcare costs associated with multi-gene panel testing for advanced cancer treatment. The impact on OS was not significant, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in-hospital deaths suggesting important considerations in determining the value of NGS panel testing for advanced cancers. Funding: T.P H holds a research grant provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (#IA-035 and P.HSR.158) and through funding of the Canadian Network for Learning Healthcare Systems and Cost-Effective 'Omics Innovation (CLEO) via Genome Canada (G05CHS).

"I just wanted more": Hereditary cancer syndromes patients' perspectives on the utility of circulating tumour DNA testing for cancer screening.

Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early. This study aimed to explore patients' perspectives on ctDNA's utility to help inform its clinical adoption and implementation. We conducted a qualitative interpretive description study using semi-structured phone interviews. Participants were purposively sampled adult HCS patients recruited from a Canadian HCS research consortium. Thirty HCS patients were interviewed (n = 19 women, age range 20s-70s, n = 25 were white). Participants were highly concerned about developing cancers, particularly those without reliable screening options for early detection. They "just wanted more" than their current screening strategies. Participants were enthusiastic about ctDNA's potential to be comprehensive (detect multiple cancers), predictive (detect cancers early) and tailored (lead to personalized clinical management). Participants also acknowledged ctDNA's potential limitations, including false positives/negatives risks and experiencing additional anxiety. However, they saw ctDNA's potential benefits outweighing its limitations. In conclusion, participants' belief in ctDNA's potential to improve their care overshadowed its limitations, indicating patients' support for using ctDNA in HCS care.

Real-World Cost Effectiveness of a Policy of KRAS Testing to Inform Cetuximab or Panitumumab for Third-Line Therapy of Metastatic Colorectal Cancer in British Columbia, Canada.

BACKGROUND: Cetuximab and panitumumab, two anti-EGFR therapies, are widely used for third-line therapy of metastatic colorectal cancer (mCRC) with wild-type KRAS, but there remains uncertainty around their cost effectiveness. The objective of this analysis was to conduct a real-world cost-effectiveness analysis of the policy change introducing KRAS testing and third-line anti-EGFR therapy mCRC in British Columbia (BC), Canada. METHODS: We conducted secondary analysis of administrative data for a cohort of mCRC patients treated in BC in 2006-2015. Patients potentially eligible for KRAS testing and third-line therapy after the policy change (July 2009) were matched 2:1 to pre-policy patients using genetic matching on propensity score and baseline covariates. Costs and survival time were calculated over an 8-year time horizon, with bootstrapping to characterize uncertainty around endpoints. Cost effectiveness was expressed using incremental cost-effectiveness ratios (ICER) and the probability of cost effectiveness at a range of thresholds. RESULTS: The cohort included 1757 mCRC patients (n = 456 pre-policy and n = 1304 post-policy; of those, n = 420 received cetuximab or panitumumab). There was a significant increase in survival and cost following the policy change. Adoption of KRAS testing and anti-EGFR therapy had an ICER of CA$73,759 per life-year gained (LYG) (95% CI 46,133-186,446). In scenario analysis, a reduction in cetuximab and panitumumab cost of at least 50% was required to make the policy change cost effective at a threshold of CA$50,000/LYG. CONCLUSION: A policy of third-line anti-EGFR therapy informed by KRAS testing may be considered cost effective at thresholds above CA$70,000/LYG. Reduction in drug costs, through price discounts or potential future biosimilars, would make anti-EGFR therapy considerably more cost effective. By using real-world data for a large cohort with long follow-up we can assess the value of a policy of KRAS testing and anti-EGFR therapy achieved in practice.

Toward Best Practices for Economic Evaluations of Tumor-Agnostic Therapies: A Review of Current Barriers and Solutions.

OBJECTIVES: Cancer therapies targeting tumor-agnostic biomarkers are challenging traditional health technology assessment (HTA) frameworks. The high prevalence of nonrandomized single-arm trials, heterogeneity, and small benefiting populations are driving outcomes uncertainty, challenging healthcare decision making. We conducted a structured literature review to identify barriers and prioritize solutions to generating economic evidence for tumor-agnostic therapies. METHODS: We searched MEDLINE and Embase for English-language studies conducting economic evaluations of tumor-agnostic treatments or exploring related challenges and solutions. We included studies published by December 2022 and supplemented our review with Canadian Agency for Drugs and Technologies in Health and National Institute for Health and Care Excellence technical reports for approved tumor-agnostic therapies. Three reviewers abstracted and summarized key methodological and empirical study characteristics. Challenges and solutions were identified through authors' statements and categorized using directed content analysis. RESULTS: Twenty-six studies met our inclusion criteria. Studies spanned economic evaluations (n = 5), reimbursement reviews (n = 4), qualitative research (n = 1), methods validations (n = 3), and commentaries or literature reviews (n = 13). Challenges encountered related to (1) the treatment setting and clinical trial designs, (2) a lack of data or low-quality data on clinical and cost parameters, and (3) an inability to produce evidence that meets HTA guidelines. Although attempted solutions centered on analytic approaches for managing missing data, proposed solutions highlighted the need for real-world evidence combined with life-cycle HTA to reduce future evidentiary uncertainty. CONCLUSIONS: Therapeutic innovation outpaces HTA evidence generation and the methods that support it. Existing HTA frameworks must be adapted for tumor-agnostic treatments to support future economic evaluations enabling timely patient access.

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey.

PURPOSE: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS. METHODS: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored. RESULTS: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology. CONCLUSION: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care.

Development and early-stage evaluation of a patient portal to enhance familial communication about hereditary cancer susceptibility testing: A patient-driven approach.

INTRODUCTION: Genetic testing for hereditary cancer syndromes (HCSs) can improve health outcomes through cancer risk mitigation strategies. Effective communication between tested individuals and their family members is key to reducing the hereditary cancer burden. Our objective was to develop a patient portal to improve familial communication for patients undergoing HCS genetic testing, followed by an early-phase evaluation. METHODS: The portal was developed following the completion of 25 semistructured interviews with individuals having undergone HCS susceptibility testing at BC Cancer. Following initial development, we recruited patients and healthcare providers to provide critical feedback informing portal refinement. Quantitative feedback was summarized using descriptive statistics, and qualitative feedback was synthesized by two reviewers who engaged in iterative discussion within the research team to prioritize recommendations for integration. RESULTS: The patient portal includes four key components consisting of (a) targeted educational information about hereditary cancer and HBOC syndrome associated risks and testing process overview, (b) a general frequently asked questions 'FAQ' page informed by the qualitative interviews, patient partner feedback, and consultation with the HCP, (c) guidance to support familial communication including a video developed with a patient partner describing their lived experience navigating the communication process and (d) a series of lay summaries of genetic test findings to support information transfer among family members. Thirteen healthcare providers and seven patients participated in user testing. Domains within which participant recommendations were provided included presentation, educational content and process clarification. CONCLUSIONS: This investigation demonstrates the value of continual integration of patient and provider preferences through the development of tools endeavouring to assist with complex genomics-informed decision-making. Our work aims to broaden the population-wide impact of HCS testing programs by improving communication processes between probands and their potentially affected family members. PATIENT OR PUBLIC CONTRIBUTION: This work involved a patient partner who was actively engaged in all aspects of the research investigation including protocol development, review and editing of all study documentation (including that of the previously published qualitative investigation), interpretation of results, as well as reviewing and editing the manuscript. Patient partners and healthcare professionals were recruited as research participants to provide critical feedback on the patient portal.

A perspective on life-cycle health technology assessment and real-world evidence for precision oncology in Canada.

Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group. In light of these challenges, mechanisms to manage precision oncology uncertainties are critical. We propose a life-cycle HTA framework and outline supporting criteria to manage uncertainties based on real world data collected from learning healthcare systems. If appropriately designed, we argue that life-cycle HTA is the driver of real world evidence generation and furthers our understanding of comparative effectiveness and value. We conclude that life-cycle HTA deliberation processes must be embedded into healthcare systems for an agile response to the constantly changing landscape of precision oncology innovation. We encourage further research outlining the core requirements, infrastructure, and checklists needed to achieve the goal of learning healthcare supporting life-cycle HTA.

Mapping the experiences of people with advanced cancer across multiple cancer types-a scoping review.

BACKGROUND: Through the introduction of tumor agnostic therapies, people with metastatic cancer and their treating physicians are facing new treatment choices that have differing side effect and efficacy profiles from conventional chemotherapy. OBJECTIVE: The present study undertakes a scoping review of research into the experiences of people with advanced or metastatic cancer across various solid tumor types with the goal of developing a tumor-agnostic conceptual model. DESIGN: Automated queries on three internet search engines were performed to identify qualitative interview studies that focused on people with metastatic cancer. No limits were imposed for dates nor location of studies. RESULTS: Of the 173 hits generated from the searches, 25 peer-reviewed papers were selected for the review with dates that ranged from 2007 to 2022. All papers originated from the USA, Europe, Australia, or Japan. Three major themes emerged that formed the basis for the tumor-agnostic conceptual model: symptoms, loss of autonomy, and adaptation/coping. CONCLUSIONS: The explication of the interplay between the physical and emotional symptoms experienced by those with advanced and metastatic cancer using a multi-tumor approach provides the potential to make generalizations about the needs of this population. An opportunity exists to potentially address these needs through matching patient needs and preferences with the characteristics of novel therapeutics. IMPLICATIONS FOR CANCER SURVIVORS: In the era of tumor agnostic therapies, the elicitation of patient preferences across the spectrum of anatomical origins has the potential to enhance shared decision making in the setting of metastatic disease.

"Game Changer": Health Professionals' Views on the Clinical Utility of Circulating Tumor DNA Testing in Hereditary Cancer Syndrome Management.

BACKGROUND: We explored health professionals' views on the utility of circulating tumor DNA (ctDNA) testing in hereditary cancer syndrome (HCS) management. MATERIALS AND METHODS: A qualitative interpretive description study was conducted, using semi-structured interviews with professionals across Canada. Thematic analysis employing constant comparison was used for analysis. 2 investigators coded each transcript. Differences were reconciled through discussion and the codebook was modified as new codes and themes emerged from the data. RESULTS: Thirty-five professionals participated and included genetic counselors (n = 12), geneticists (n = 9), oncologists (n = 4), family doctors (n = 3), lab directors and scientists (n = 3), a health-system decision maker, a surgeon, a pathologist, and a nurse. Professionals described ctDNA as "transformative" and a "game-changer". However, they were divided on its use in HCS management, with some being optimistic (optimists) while others were hesitant (pessimists). Differences were driven by views on 3 factors: (1) clinical utility, (2) ctDNA's role in cancer screening, and (3) ctDNA's invasiveness. Optimists anticipated ctDNA testing would have clinical utility for HCS patients, its role would be akin to a diagnostic test and would be less invasive than standard screening (eg imaging). Pessimistic participants felt ctDNA testing would add limited utility; it would effectively be another screening test in the pathway, likely triggering additional investigations downstream, thereby increasing invasiveness. CONCLUSIONS: Providers anticipated ctDNA testing will transform early cancer detection for HCS families. However, the contrasting positions on ctDNA's role in the care pathway raise potential practice variations, highlighting a need to develop evidence to support clinical implementation and guidelines to standardize adoption.

The impact of whole genome and transcriptome analysis (WGTA) on predictive biomarker discovery and diagnostic accuracy of advanced malignancies.

In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non-MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non-contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

FDA Accelerated Approval for Malignant Hematology and Oncology Indications in the Canadian Environment.

Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA AA cancer therapies in Canada. The FDA's AA of malignant hematology and oncology from January 2000-December 2019 was reviewed. Dates from Health Canada, HTA decisions and provincial listings were collected. There were 94 FDA AAs, two of which were subsequently withdrawn. Of the 92 AAs, 70 received full (46)/conditional (24) Health Canada approval, and 22 were not filed. Since the introduction of HTA, 31 out of 45 of Health Canada's approved indications underwent HTA review: 18 received a positive recommendation conditional on cost-effectiveness, 8 were not recommended and 5 were withdrawn/suspended. The median time from the AA to any Health Canada approval is 9.4 months, from any Health Canada approval to HTA decision is 5.8 months and from HTA decision to the first formulary listing is 12.0 months. The access and timeline for the first formulary listing differences were observed between the USA and Canada due to the decision of pharmaceutical companies to submit (or not) to regulatory/HTA bodies, national procedural delays with different healthcare delivery models and submission timelines. This study demonstrates that there is delayed access to promising new therapies in Canada.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

OBJECTIVES: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. METHODS: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. RESULTS: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. CONCLUSIONS: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.

Cost-Effectiveness of Molecularly Guided Treatment in Diffuse Large B-Cell Lymphoma (DLBCL) in Patients under 60.

BACKGROUND: Classifying diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes could allow for personalized cancer control. Evidence suggests that subtype-guided treatment may be beneficial in the activated B-cell (ABC) subtype of DLBCL, among patients under the age of 60. METHODS: We estimated the cost-effectiveness of age- and subtype-specific treatment guided by gene expression profiling (GEP). A probabilistic Markov model examined costs and quality-adjusted life-years gained (QALY) accrued to patients under GEP-classified COO treatment over a 10-year time horizon. The model was calibrated to evaluate the adoption of ibrutinib as a first line treatment among patients under 60 years with ABC subtype DLBCL. The primary data source for efficacy was derived from published estimates of the PHOENIX trial. These inputs were supplemented with patient-level, real-world data from BC Cancer, which provides comprehensive cancer services to the population of British Columbia. RESULTS: We found the cost-effectiveness of GEP-guided treatment vs. standard care was $77,806 per QALY (24.3% probability of cost-effectiveness at a willingness-to-pay (WTP) of $50,000/QALY; 53.7% probability at a WTP of $100,000/QALY) for first-line treatment. Cost-effectiveness was dependent on assumptions around decision-makers' WTP and the cost of the assay. CONCLUSIONS: We encourage further clinical trials to reduce uncertainty around the implementation of GEP-classified COO personalized treatment in this patient population.

Stakeholder Perspectives on Navigating Evidentiary and Decision Uncertainty in Precision Oncology.

(1) Background: Precision oncology has the potential to improve patient health and wellbeing through targeted prevention and treatment. Owing to uncertain clinical and economic outcomes, reimbursement has been limited. The objective of this pan-Canadian qualitative study was to investigate barriers to precision oncology implementation from the perspectives of health system stakeholders. (2) Methods: We conducted 32 semi-structured interviews with health technology decision makers (n = 14) and clinicians (n = 18) experienced with precision oncology. Participants were recruited using a purposive sampling technique. Interviews were analyzed using thematic analysis. Recruitment continued until two qualitative analysts reached agreement that thematic saturation was reached. (3) Results: While cautiously optimistic about the potential for enhanced therapeutic alignment, participants identified multiple decisional challenges under conditions of evidentiary uncertainty. Decision makers voiced concern over resource requirements alongside small benefitting patient populations and limited evidence supporting patient and health system impacts. Clinicians were comparatively tolerant of evidentiary uncertainty guiding clinical decision-making practices. Clinicians applied a broader definition of patient benefit, focusing on the ability to assist patients making informed clinical decisions. (4) Conclusions: Sustainable precision oncology must balance demand with evidence demonstrating benefit. We show that clinicians and decision makers vary in their tolerance for evolving knowledge, suggesting a need to establish evidentiary standards supporting precision oncology reimbursement decisions.

Early-stage economic analysis of research-based comprehensive genomic sequencing for advanced cancer care.

Genomic research is driving discovery for future population benefit. Limited evidence exists on immediate patient and health system impacts of research participation. This study uses real-world data and quasi-experimental matching to examine early-stage cost and health impacts of research-based genomic sequencing. British Columbia's Personalized OncoGenomics (POG) single-arm program applies whole genome and transcriptome analysis (WGTA) to characterize genomic landscapes in advanced cancers. Our cohort includes POG patients enrolled between 2014 and 2015 and 1:1 genetic algorithm-matched usual care controls. We undertake a cost consequence analysis and estimate 1-year effects of WGTA on patient management, patient survival, and health system costs reported in 2015 Canadian dollars. WGTA costs are imputed and forecast using system of equations modeling. We use Kaplan-Meier survival analysis to explore survival differences and inverse probability of censoring weighted linear regression to estimate mean 1-year survival times and costs. Non-parametric bootstrapping simulates sampling distributions and enables scenario analysis, revealing drivers of incremental costs, survival, and net monetary benefit for assumed willingness to pay thresholds. We identified 230 POG patients and 230 matched controls for cohort inclusion. The mean period cost of research-funded WGTA was $26,211 (SD: $14,191). Sequencing costs declined rapidly, with WGTA forecasts hitting $13,741 in 2021. The incremental healthcare system effect (non-research expenditures) was $5203 (95% CI: 75, 10,424) compared to usual care. No overall survival differences were observed, but outcome heterogeneity was present. POG patients receiving WGTA-informed treatment experienced incremental survival gains of 2.49 months (95% CI: 1.32, 3.64). Future cost consequences became favorable as WGTA cost drivers declined and WGTA-informed treatment rates improved to 60%. Our study demonstrates the ability of real-world data to support evaluations of only-in-research health technologies. We identify situations where precision oncology research initiatives may produce survival benefit at a cost that is within healthcare systems' willingness to pay. This economic evidence informs the early-stage healthcare impacts of precision oncology research.

Utility maximization versus regret minimization in health choice behavior: Evidence from four datasets.

Choice models in health are almost exclusively based on the neoclassical economic paradigm of utility maximization. Recently developed choice models have captured and shown empirical support for regret minimization as an alternative decision rule. In health economics, recent applications of RRM models indicate that individuals making health-based choices may exhibit regret minimization-type behavior. In this paper, we build on this research using a more flexible model that allows for heterogeneous decision rules, separately from preference heterogeneity, and comparing it to models that assume single decision rules. We use four datasets from diverse settings in which individuals make health choices: tobacco markets, genomic testing, and HIV prevention. We found that, if a one-size-fits-all rule is applied, then utility maximization was preferable to regret minimization for these datasets. However, we also find that individuals apply varying decision rules in similar proportions in these health settings, suggesting that models for heterogeneous decision rules were needed to capture these behaviors in these settings.

The Past, Present, and Future of Economic Evaluations of Precision Medicine at the Committee for Economic Analyses of the Canadian Cancer Trials Group.

Precision medicine in oncology poses unique challenges to the generation of clinical and economic evidence used for cost-effectiveness analyses that can inform health technology assessment. The conduct of randomized controlled trials for biomarker-specific therapies targeted towards small populations has limitations in regard to feasibility, timeliness, and cost. These limitations result in associated challenges for groups involved in the generation of economic evidence to inform treatment-related decision making, including the Committee of Economic Analysis (CEA) at the Canadian Cancer Trials Group (CCTG). We provide a high-level description and vision about the new paradigm of clinical trial design, generation of economic evidence, and novel approaches to economic evaluations necessary in the space of precision medicine in oncology in Canada. The CEA's previous approach to precision medicine, including master protocol designs and single-arm studies, is reviewed. Methods and approaches currently under consideration by the CEA and national collaborators, such as the role of real-world and clinical trial evidence in enabling life-cycle assessment of therapies, are explored. Finally, future initiatives being planned in the space of precision medicine at CCTG, such as the incorporation of correlative studies to identify and test high-performing biomarkers in trials, are discussed.

Patient and public preferences for being recontacted with updated genomic results: a mixed methods study.

Variants of uncertain significance (VUS) are frequently reclassified but recontacting patients with updated results poses significant resource challenges. We aimed to characterize public and patient preferences for being recontacted with updated results. A discrete choice experiment (DCE) was administered to representative samples of the Canadian public and cancer patients. DCE attributes were uncertainty, cost, recontact modality, choice of results, and actionability. DCE data were analyzed using a mixed logit model and by calculating willingness to pay (WTP) for types of recontact. Qualitative interviews exploring recontact preferences were analyzed thematically. DCE response rate was 60% (n = 1003, 50% cancer patient participants). 31 participants were interviewed (11 cancer patients). Interviews revealed that participants expected to be recontacted. Quantitatively, preferences for how to be recontacted varied based on certainty of results. For certain results, WTP was highest for being recontacted by a doctor with updates ($1075, 95% CI: $845, $1305) and for contacting a doctor to request updates ($1038, 95% CI: $820, $1256). For VUS results, WTP was highest for an online database ($1735, 95% CI: $1224, $2247) and for contacting a doctor ($1705, 95% CI: $1102, $2307). Qualitative data revealed that preferences for provider-mediated recontact were influenced by trust in healthcare providers. Preferences for a database were influenced by lack of trust in providers and desire for control. Patients and public participants support an online database (e.g. patient portal) to recontact for VUS, improving feasibility, and provider-mediated recontact for certain results, consistent with usual care.

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiotherapy for the Treatment of Oligometastatic Tumors versus Standard of Care.

BACKGROUND: Recent clinical trial results reported that stereotactic radiotherapy (SABR) may improve survival for patients with oligometastatic (OM) cancer. Given that these results come from a phase II trial, there remains considerable uncertainty about this finding, and about the cost-effectiveness of SABR for patients with OM cancer. In this analysis, we estimate the cost-effectiveness of SABR for oligometastatic cancer patients. METHODS: A probabilistic time-dependent Markov model was constructed to simulate treatment of oligometastatic cancer patients over five- and ten-year time horizons. The primary data source was the phase II, Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET )trial and supplemented with data from the literature. We estimated the effect of SABR and the standard of care (SoC) using quality-adjusted life-years (QALYs). Costs were measured from a provincial payer perspective (2018 Canadian dollars). RESULTS: In the reference case analysis (five-year time horizon), SABR was associated with additional incremental costs of CAD 38,487 and an incremental QALY gain of 0.84. This resulted in an incremental cost-effectiveness ratio (ICER) of CAD 45,726 per QALY gained. Over a ten-year time horizon, the increased uncertainty in the long-term effectiveness of SABR resulted in an ICER of CAD 291,544 per QALY gained. Estimates from the probabilistic analysis indicated that at a willingness-to-pay (WTP) threshold of CAD 50,000 and CAD 100,000 per QALY gained, there is 54% and 78% probability (respectively) that SABR would be cost-effective using the five-year time horizon. CONCLUSIONS: The adoption of SABR therapy requires a considerable upfront capital investment. Our results suggest that the cost-effectiveness of SABR is contingent on the uncertainty in the evidence base. Further clinical trials to confirm the effectiveness of SABR and research into the real-world costs associated with this treatment could reduce the uncertainty around implementation of the technology.