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. RESULTS: Through SOC, 49.4% (95% CI: 40.6, 58.2) of patients were diagnosed at an average cost of C$11,683 per patient (95% CI: 9200, 14,166). Compared with SOC, earlier ES or GS access yielded similar or improved diagnostic rates and shorter times to genetic diagnosis, with 94% of simulations demonstrating cost savings for streamlined ES and 60% for first-tier GS. Net benefit from the perspective of the health care system was C$2956 (95% CI: -608, 6519) for streamlined ES compared with SOC. CONCLUSION: Using real-world data, we found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared with current practice in a Canadian health care system.

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.

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.

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. We examine performance by comparing the proposed extension against baseline propensity score matching and time-dependent propensity score matching. METHODS: To evaluate comparative performance, we developed a Monte Carlo simulation framework that reflects a static treatment assigned at multiple time points. Data generation considers a treatment assignment model, a continuous outcome model, and underlying covariates. In simulation, we generated 1,000 datasets, each consisting of 1,000 subjects, and applied: (1) nearest neighbour matching on time-invariant, baseline propensity scores; (2) sequential risk set matching on time-dependent propensity scores; and (3) longitudinal genetic matching on time-dependent covariates. To measure comparative performance, we estimated covariate balance, efficiency, bias, and root mean squared error (RMSE) of treatment effect estimates. In scenario analysis, we varied underlying assumptions for assumed covariate distributions, correlations, treatment assignment models, and outcome models. RESULTS: In all scenarios, baseline propensity score matching resulted in biased effect estimation in the presence of time-dependent confounding, with mean bias ranging from 29.7% to 37.2%. In contrast, time-dependent propensity score matching and longitudinal genetic matching achieved stronger covariate balance and yielded less biased estimation, with mean bias ranging from 0.7% to 13.7%. Across scenarios, longitudinal genetic matching achieved similar or better performance than time-dependent propensity score matching without requiring manual re-specifications or normality of covariates. CONCLUSIONS: While the most appropriate longitudinal method will depend on research questions and underlying data patterns, our study can help guide these decisions. Simulation results demonstrate the validity of our longitudinal genetic matching approach for supporting future real-world assessments of treatments accessible at multiple time points.

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.

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. METHODS: All patients who completed breast screening between April 1st, 2017 and March 31st, 2021 were eligible to participate. An average of 3 annual periods between April 1st, 2017 and March 31st, 2020 were defined as the pre-COVID period while the period between April 1st, 2020 and March 31st, 2021 was defined as the COVID-impacted period. The Postal CodeOM Conversion File Plus was applied to map patient residential postal codes to 2016 census standard geographical areas, which provided information on community size, income quintile and dissemination areas. Dissemination areas were subsequently linked to the Canadian Index of Multiple Deprivation (CIMD). RESULTS: Overall BSV was reduced by 23.0% during the COVID-impacted period as compared to the pre-COVID period. Percent reductions in BSVs were greatest among younger patients aged 40 to 49 years (31.3%) and patients residing in communities with a population of less than 10,000 (27.0%). Percent reduction in BSV was greatest among patients in the lowest income quintile (28.1%). Percent reductions in BSVs were greatest for patients in the most deprived quintiles across all 4 dimensions of the CIMD. CONCLUSION: Disproportionate reductions in BSVs were observed during the COVID-19 pandemic among younger patients, patients residing in rural communities, patients in lower income quintiles, and patients in the most deprived quintiles across all 4 dimensions of the CIMD.

"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.

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.

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.

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. The objective of this review was to characterize patient and public preferences for secured data sharing platforms and incentives to share real-world data for health research. We conducted a scoping review of the data sharing and health informatics literature capturing patient and public values for data sharing platforms and incentivization. We searched Embase and Medline (OVID) databases for primary data studies. Two reviewers participated in study selection and data abstraction. Findings were summarized according to preference frequency within each major theme. The final search produced 253 articles. After screening, 12 articles were included for data extraction. Two studies discussed preferences for data sharing platforms, 7 discussed incentives preferences, and 3 addressed both. We identified considerable variation of patient and public preferences according to preferred consent mechanisms and level of control, willingness to trade off risks and benefits, and the type of incentivization appropriate to offer for participation. This preference variation informs the conditions under which individuals may be willing to engage with secured data sharing platforms to support research. Our findings indicate that platforms will need to be flexible to meet the diverse preferences of users and facilitate uptake.

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.

Describing practices of priority setting and resource allocation in publicly funded health care systems of high-income countries.

BACKGROUND: Healthcare spending has grown over the last decades in all developed countries. Making hard choices for investments in a rational, evidence-informed, systematic, transparent and legitimate manner constitutes an important objective. Yet, most scientific work in this area has focused on developing/improving prescriptive approaches for decision making and presenting case studies. The present work aimed to describe existing practices of priority setting and resource allocation (PSRA) within the context of publicly funded health care systems of high-income countries and inform areas for further improvement and research. METHODS: An online qualitative survey, developed from a theoretical framework, was administered with decision-makers and academics from 18 countries. 450 individuals were invited and 58 participated (13% of response rate). RESULTS: We found evidence that resource allocation is still largely carried out based on historical patterns and through ad hoc decisions, despite the widely held understanding that decisions should be based on multiple explicit criteria. Health technology assessment (HTA) was the tool most commonly indicated by respondents as a formal priority setting strategy. Several approaches were reported to have been used, with special emphasis on Program Budgeting and Marginal Analysis (PBMA), but limited evidence exists on their evaluation and routine use. Disinvestment frameworks are still very rare. There is increasing convergence on the use of multiple types of evidence to judge the value of investment options. CONCLUSIONS: Efforts to establish formal and explicit processes and rationales for decision-making in priority setting and resource allocation have been still rare outside the HTA realm. Our work indicates the need of development/improvement of decision-making frameworks in PSRA that: 1) have well-defined steps; 2) are based on multiple criteria; 3) are capable of assessing the opportunity costs involved; 4) focus on achieving higher value and not just on adoption; 5) engage involved stakeholders and the general public; 6) make good use and appraisal of all evidence available; and 6) emphasize transparency, legitimacy, and fairness.

Health-related quality of life in oncology drug reimbursement submissions in Canada: A review of submissions to the pan-Canadian Oncology Drug Review.

BACKGROUND: In Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH) evaluates and makes recommendations for the reimbursement of cancer drugs. One component of its recommendation is based on an economic evaluation, which typically takes the form of a cost-utility analysis. A cost-utility analysis measures the effects of competing therapies with quality-adjusted life-years (QALYs). The data for this calculation typically come from generic, preference-based measures of health-related quality of life (HRQOL). The objective of this review is to determine the frequency at which HRQOL data are collected alongside cancer drug trials and used in the cost-utility analysis submitted to the CADTH pan-Canadian Oncology Drug Review (pCODR). METHODS: Submissions between 2015 and 2018 to pCODR, the group charged with evaluating cancer drug submissions at CADTH, were reviewed. All pCODR submissions, either in progress or completed, were publicly available online. The search was restricted to completed evaluations. RESULTS: Forty-three submissions met the inclusion criteria. The incremental gain in QALYs in most submissions from the new technology was small (median incremental gain, 0.86; interquartile range, 0.6-1.39). More than half of the submissions (56%) did not include original data on HRQOL, with most relying on previous studies of variable relevance and quality. Re-analyses by pCODR based on concerns over HRQOL data used in the submitted model were common (52%). CONCLUSIONS: Drug manufacturers do not consistently collect data on HRQOL alongside clinical trials and instead rely on evidence generated in previous studies to inform cost-utility analyses. These findings should induce manufacturers to collect original HRQOL data that are simultaneously relevant to patients and decision makers.

Health-care practitioners' preferences for the return of secondary findings from next-generation sequencing: a discrete choice experiment.

PURPOSE: Health-care practitioners' (HCPs) preferences for returning secondary findings (SFs) will influence guideline compliance, shared decision-making, and patient health outcomes. This study aimed to estimate HCPs' preferences and willingness to support the return (WTSR) of SFs in Canada. METHODS: A discrete choice experiment estimated HCPs' preferences for the following attributes: disease risk, clinical utility, health consequences, prior experience, and patient preference. We analyzed responses with an error component mixed logit model and predicted WTSR using scenario analyses. RESULTS: Two hundred fifty participants of 583 completed the questionnaire (completion rate: 42.9%). WTSR was significantly influenced by patient preference and SF outcome characteristics. HCPs' WTSR was 78% (95% confidence interval: 74-81%) when returning SFs with available medical treatment, high penetrance, severe health consequences, and patient's preference for return. Genetics professionals had a higher WTSR than HCPs of other types when returning SFs with clinical utility and patient preference to know. HCPs >55 years of age were more likely to return SFs compared with younger HCPs. CONCLUSION: This study identified factors that influence WTSR of SFs and indicates that HCPs make tradeoffs between patient preference and other outcome characteristics. The results can inform clinical scenarios and models aiming to understand shared decision-making, patient and family opportunity to benefit, and cost-effectiveness.

Heterogeneous Patient Preferences for Modern Antiretroviral Therapy: Results of a Discrete Choice Experiment.

OBJECTIVE: Limited data describe patient preferences for the growing number of antiretroviral therapies (ARTs). We quantified preferences for key characteristics of modern ART deemed relevant to shared decision making. METHODS: A discrete choice experiment survey elicited preferences for ART characteristics, including dosing (frequency and number of pills), administration characteristics (pill size and meal requirement), most bothersome side effect (from diarrhea, sleep disturbance, headaches, dizziness/difficulty thinking, depression, or jaundice), and most bothersome long-term effect (from increased risk of heart attacks, bone fractures, renal dysfunction, hypercholesterolemia, or hyperglycemia). Between March and August 2017, the discrete choice experiment was fielded to 403 treatment-experienced persons living with human immunodeficiency virus (HIV), enrolled from 2 infectious diseases clinics in the southern United States and a national online panel. Participants completed 16 choice tasks, each comparing 3 treatment options. Preferences were analyzed using mixed and latent class logit models. RESULTS: Most participants were male (68%) and older (interquartile range: 42-58 years), and had substantial treatment experience (interquartile range: 7-21 years). In mixed logit analyses, all attributes were associated with preferences. Side and long-term effects were most important, with evidence of substantial preference heterogeneity. Latent class analysis identified 5 preference classes. For classes 1 (40%), 2 (24%), and 3 (21%), side effects were most important, followed by long-term effects. For class 4 (10%), dosing was most important. Class 5 (4%) was largely indifferent to ART characteristics. CONCLUSION: Overall, treatment-experienced persons living with HIV valued minimizing side effects and long-term toxicities over dosing and administration characteristics. Preferences varied widely, highlighting the need to elicit individual patient preferences in models of shared antiretroviral decision making.

Addressing Challenges of Economic Evaluation in Precision Medicine Using Dynamic Simulation Modeling.

OBJECTIVES: The objective of this article is to describe the unique challenges and present potential solutions and approaches for economic evaluations of precision medicine (PM) interventions using simulation modeling methods. METHODS: Given the large and growing number of PM interventions and applications, methods are needed for economic evaluation of PM that can handle the complexity of cascading decisions and patient-specific heterogeneity reflected in the myriad testing and treatment pathways. Traditional approaches (eg, Markov models) have limitations, and other modeling techniques may be required to overcome these challenges. Dynamic simulation models, such as discrete event simulation and agent-based models, are used to design and develop mathematical representations of complex systems and intervention scenarios to evaluate the consequence of interventions over time from a systems perspective. RESULTS: Some of the methodological challenges of modeling PM can be addressed using dynamic simulation models. For example, issues regarding companion diagnostics, combining and sequencing of tests, and diagnostic performance of tests can be addressed by capturing patient-specific pathways in the context of care delivery. Issues regarding patient heterogeneity can be addressed by using patient-level simulation models. CONCLUSION: The economic evaluation of PM interventions poses unique methodological challenges that might require new solutions. Simulation models are well suited for economic evaluation in PM because they enable patient-level analyses and can capture the dynamics of interventions in complex systems specific to the context of healthcare service delivery.

Genetic testing for hereditary cancer syndromes: patient recommendations for improved risk communication.

BACKGROUND: Multi-gene panel testing is replacing single-gene testing for patients with suspected hereditary cancer syndromes. The detection of a hereditary cancer syndrome allows tested individuals to initiate enhanced primary and secondary prevention efforts-where available-with a view to reduce disease burden. Current policy prevents testing programmes from communicating genetic test results with potentially affected family members, yet it is well documented that tested individuals face multiple challenges in initiating such discussions with relatives. OBJECTIVE: In response to this challenge, we sought patient recommendations about how to improve genetic risk communication to enhance interfamilial discussions about primary and secondary disease prevention. DESIGN: We conducted 25 semi-structured interviews with individuals who received genetic testing through British Columbia's Hereditary Cancer Program between 2017 and 2018. Interviews were professionally transcribed and analysed using a constant comparative approach. RESULTS: Participants described difficulty engaging in conversations with relatives who were resistant to receiving genetic risk information, when communicating with younger relatives and where participants reported strained familial relationships. Participants recommended that testing facilities provide a summary of results and implications and that resources be made available to prepare patients for challenging discussions with family members. DISCUSSION: Our study demonstrates that individuals undergoing genetic testing for suspected hereditary cancer syndromes would benefit from additional supportive resources alongside genetic counselling. Providing this on-going support will enhance the accurate and transparent communication of risk to facilitate the uptake of cascade testing and enhanced prevention strategies.

Public perspectives on disinvestments in drug funding: results from a Canadian deliberative public engagement event on cancer drugs.

BACKGROUND: Decisions relating to the funding of new drugs are becoming increasingly challenging due to a combination of aging populations, rapidly increasing list prices, and greater numbers of drug-indication pairs being brought to market. This is especially true in cancer, where rapid list price inflation is coupled with steeply rising numbers of incident cancer cases. Within a publicly funded health care system, there is increasing recognition that resource allocation decisions should consider the reassessment of, and potential disinvestment from, currently funded interventions alongside new investments. Public input into the decision-making process can help legitimize the outcomes and ensure priority-setting processes are aligned with public priorities. METHODS: In September 2014, a public deliberation event was held in Vancouver, Canada, to obtain public input on the topic of cancer drug funding. Twenty-four members of the general public were tasked with making collective recommendations for policy-makers about the principles that should guide funding decisions for cancer drugs in the province of British Columbia. Deliberative questions and decision aids were used to elicit individuals' willingness to make trade-offs between expenditures and health outcomes. RESULTS: Participants discussed the implications of disinvestment decisions from cancer drugs in terms of its impact on patient choice, fairness and quality of life. Their discussions indicate that in order for a decision to disinvest from currently-funded cancer drugs to be acceptable, it must align with three main principles: the decision must be accompanied by significant gains, described both in terms of cost savings and opportunities to re-invest elsewhere in the health care system; those who are currently prescribed a cancer drug should be allowed to continue their course of treatment (referred to as a continuance clause, or "grandfathering" approach); and it must consider how access to care for specialized populations is impacted. CONCLUSIONS: The results from this deliberation event provide insight into what is acceptable to British Columbians with respect to disinvestment decisions for cancer drugs. These recommendations can be considered within wider health system decision-making frameworks for funding decisions relating to all drugs, as well as for cancer drugs.

The Feelings About genomiC Testing Results (FACToR) Questionnaire: Development and Preliminary Validation.

The purpose of this study was to develop a brief instrument, the Feelings About genomiC Testing Results (FACToR), to measure the psychosocial impact of returning genomic findings to patients in research and clinical practice. To create the FACToR, we modified and augmented the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire based on findings from a literature review, two focus groups (N = 12), and cognitive interviews (N = 6). We evaluated data from 122 participants referred for evaluation for inherited colorectal cancer or polyposis from the New EXome Technology in (NEXT) Medicine Study, an RCT of exome sequencing versus usual care. We assessed floor and ceiling effects of each item, conducted principal component analysis to identify subscales, and evaluated each subscale's internal consistency, test-retest reliability, and construct validity. After excluding items that were ambiguous or demonstrated floor or ceiling effects, 12 items forming four distinct subscales were retained for further analysis: negative emotions, positive feelings, uncertainty, and privacy concerns. All four showed good internal consistency (0.66-0.78) and test-retest reliability (0.65-0.91). The positive feelings and the uncertainty subscales demonstrated known-group validity. The 12-item FACToR with four subscales shows promising psychometric properties on preliminary evaluation in a limited sample and needs to be evaluated in other populations.