Heuristics Identified in Health Data-Sharing Preferences of Patients With Cancer: Qualitative Focus Group Study.

Background: Evaluating precision oncology outcomes requires access to real-world and clinical trial data. Access is based on consent, and consent is based on patients' informed preferences when deciding to share their data. Decision-making is often modeled using utility theory, but a complex decision context calls for a consideration of how heuristic, intuitive thought processes interact with rational utility maximization.

Using Genomic Heterogeneity to Inform Therapeutic Decisions for Metastatic Colorectal Cancer: An Application of the Value of Heterogeneity Framework.

Background And Objective: Mutations in KRAS and NRAS are predictive of poor response to cetuximab and panitumumab, two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies used in metastatic colorectal cancer (mCRC). Our objective was to explore the value of using KRAS and NRAS mutation status to inform third-line anti-EGFR therapy for mCRC using the value of heterogeneity (VOH) framework.

Methods: We used administrative data to identify mCRC patients who were potentially eligible for third-line therapy in 2006-2019 in British Columbia (BC), Canada.

Qualitative genomic research with Indigenous peoples: a scoping review of participatory practice.

Introduction: Indigenous peoples and perspectives are under-represented within genomic research. Qualitative methods can help redress this under-representation by informing the development of inclusive genomic resources aligned with Indigenous rights and interests. The difficult history of genomic research with Indigenous peoples requires that research be conducted responsibly and collaboratively.

Addressing immortal time bias in precision medicine: Practical guidance and methods development.

Objective: To compare theoretical strengths and limitations of common immortal time adjustment methods, propose a new approach using multiple imputation (MI), and provide practical guidance for using MI in precision medicine evaluations centered on a real-world case study.

Study Setting And Design: Methods comparison, guidance, and real-world case study based on previous literature. We compared landmark analysis, time-distribution matching, time-dependent analysis, and our proposed MI application.

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences for Enhanced Data Sharing for Precision Oncology.

Purpose: In Canada, health data are siloed, slowing bioinnovation and evidence generation for personalized cancer care. Secured data-sharing platforms (SDSPs) can enable data analysis across silos through rapid concatenation across trial and real-world settings and timely researcher access. To motivate patient participation and trust in research, it is critical to ensure that SDSP design and oversight align with patients' values and address their concerns.

Next-generation sequencing in oncology: challenges in economic evaluations.

Introduction: Next-generation sequencing (NGS) identifies genetic variants to inform personalized treatment plans. Insufficient evidence of cost-effectiveness impedes the integration of NGS into routine cancer care. The complexity of personalized treatment challenges conventional economic evaluation.

Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis.

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care.

Real-world cost-effectiveness of panel-based genomic testing to inform therapeutic decisions for metastatic colorectal cancer.

Background: Mutations in KRAS and NRAS are associated with a lack of response to cetuximab and panitumumab, two biologics used for third-line therapy of metastatic colorectal cancer (mCRC). In British Columbia, Canada, eligibility for cetuximab or panitumumab was first based on single-gene KRAS testing. OncoPanel, a multi-gene next-generation sequencing panel with both KRAS and NRAS, was introduced in 2016.

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada.

Importance: Etiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs.

Objective: To measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases.

Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse.

Development of a Value Assessment Framework for Pediatric Health Technologies Using Multicriteria Decision Analysis: Expanding the Value Lens for Funding Decision Making.

Objectives: A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach.

Methods: We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework.

Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: Evidence from Canada.

Purpose: To determine real-world diagnostic rates, cost trajectories, and cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children with developmental and/or seizure disorders in British Columbia, Canada.

Methods: Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at British Columbia Children's Hospital. Results informed a state-transition Markov model examining cost-effectiveness of 3 competing diagnostic strategies: (1) SOC with last-tier access to ES, (2) streamlined ES access, and (3) first-tier GS.

"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.

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.

Evaluation of the Association Between Sociodemographic Status and Breast Screening Volumes During the COVID-19 Pandemic in a Provincial, Population-Based Organized Breast Screening Program.

Objectives: We sought to evaluate the association between patient sociodemographic status and breast screening volumes (BSVs) during the COVID-19 pandemic in a large, population-based breast screening program that serves a provincial population of over 5 million. All patients who completed breast screening between April 1, 2017 and March 31, 2021 were eligible to participate. An average of 3 annual periods between April 1, 2017 and March 31, 2020 were defined as the pre-COVID period while the period between April 1, 2020 and March 31, 2021 was defined as the COVID-impacted period.

Genetic matching for time-dependent treatments: a longitudinal extension and simulation study.

Background: Longitudinal matching can mitigate confounding in observational, real-world studies of time-dependent treatments. To date, these methods have required iterative, manual re-specifications to achieve covariate balance. We propose a longitudinal extension of genetic matching, a machine learning approach that automates balancing of covariate histories.

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.

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.

Expensive Drugs for Rare Diseases in Canada: Time for Action Everywhere and by Everyone.

Expensive drugs for rare diseases pose unique economic, evidentiary and ethical challenges, and these will continue to escalate unless steps are taken urgently to address these challenges. We propose concrete actions that all stakeholders (federal and provincial/territorial governments, patients, healthcare providers, the public and drug manufacturers) could take now as a first step toward enhancing sustainability in the use of innovative (albeit expensive) therapies within our publicly funded healthcare system.

Expensive Drugs for Rare Diseases in Canada: What Value and at What Cost?

There has been explosive growth in the market for expensive drugs for rare diseases (EDRDs). Traditional standards of evidence are not achievable for rare diseases, so lower standards are applied. The price of these drugs is extremely high.

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.

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.

Developing Data Sharing Models for Health Research with Real-World Data: A Scoping Review of Patient and Public Preferences.

For researchers to realize the benefits of real-world data in healthcare requires broader access to patient data than is currently possible given siloed data systems. To facilitate evidence generation, infrastructure must support integrated data collection and sharing enabled by patient consent. Critical to the success of data sharing is to design secured data sharing platforms around patient preferences and expectations.