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Objectives: To analyze work productivity loss and costs, including absenteeism (time missed from work), presenteeism (reduced productivity while working), and unpaid work loss, among a sample of employed people with multiple sclerosis (pwMS) in Canada, as well as its association with clinical, sociodemographic, and work-related factors. Methods: We used cross-sectional data collected as part of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) and information from the Valuation of Lost Productivity questionnaire. Results: Among 512 pwMS who were employed, 97% showed no or mild disability and 55% experienced productivity loss due to MS in the prior 3 months. Total productivity time loss over a 3-month period averaged 60 hours (SD = 107; 23 from presenteeism, 19 from absenteeism, and 18 from unpaid work), leading to a mean cost of lost productivity of CAD$2480 (SD = 4282) per patient, with an hourly paid productivity loss greater than the wage loss. Fatigue retained significant associations with all productivity loss outcomes. Conclusion: Unpaid work loss and productivity losses exceeding those of the employee alone (due to teamwork and associated factors) are key additional contributors of the high economic burden of MS. Workplace accommodations and treatments targeted at fatigue could lessen the economic impact of MS.

BackgroundLow-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit–harm balance of this treatment has not been well studied.MethodsA probabilistic Markov model of COPD was created to simulate the course of COPD over 20 years. The model was populated with evidence from the literature and dedicated data analysis. The benefit of azithromycin was modelled as a reduction in exacerbation rates. Adverse events, including cardiovascular events, hearing loss, gastrointestinal symptoms and antimicrobial resistance (leading to a gradual decline in the effectiveness of azithromycin), were considered. All outcomes were assigned a health-related utility weight to estimate the overall net change in the quality-adjusted life year (QALY) associated with the use of azithromycin.ResultsIn patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) among the ‘frequent exacerbator’ subgroup. Azithromycin was not net beneficial among those without any moderate/severe exacerbations in the previous year. Findings were robust against series of sensitivity, scenario and threshold analyses.ConclusionsLong-term therapy with azithromycin confers a net benefit to ex-smoker patients with COPD with a recent history of exacerbations and an even larger benefit to those who are frequent exacerbators.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS), a leading cause of nontraumatic neurologic disability in young adults, exerts a substantial economic burden on the health care system. The objective of this study was to quantify the excess health care costs of MS in British Columbia, Canada. METHODS: A retrospective-matched cohort study of patients with MS was conducted using population-based administrative health data from 2001 to 2020. Patients with MS who satisfied a validated case definition were matched to 5 unique controls without MS on sex, age, and cohort entry date. Patients and controls were followed to the end of 2020 or to their last health care resource use, whichever came first. We calculated the direct medical costs for each individual, including outpatient services use, hospital admissions, and dispensed medications. We used generalized linear models with an identity link and normal distribution to estimate the excess cost of MS as the mean cost difference between patients with MS and controls. All costs were reported in 2020 Canadian dollars. RESULTS: A total of 17,071 patients with MS were matched to 85,355 controls. Overall, 72.4% were female, and the mean age at cohort entry date was 46.1 years. The excess cost of MS was $6,881 (95% CI: $6,713, $7,049) per patient-year. Inpatient, outpatient, and medication costs accounted for 25%, 10%, and 65% of excess costs, respectively. Excess costs were higher in patients with MS with at least one disease-modifying therapy (DMT) prescription ($13,267; 95% CI: $12,992–$13,542) compared with non-DMT users ($3,469; 95% CI: $3,297–$3,641) and even higher among frequent DMT users ($24,835; 95% CI: $24,528–$25,141). Patients with MS with a history of at least one relapse requiring hospitalization had higher excess costs ($10,543; 95% CI: $10,136–$10,950) compared with patients with MS without a relapse; hospitalizations accounted for 51% of the costs in this group. The excess cost of hospitalizations was $1,391 lower among frequent DMT users than non-DMT users. DISCUSSION: The economic burden of MS is considerable, with medications, particularly DMTs, being the largest cost driver. Future studies should investigate how disease management strategies, including early diagnosis and timely use of DMTs, could offset future and ongoing costs while improving patients' quality of life.

When genetic tests are not funded publicly, out-of-pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving12,000 patients/year (The Hereditary Cancer Program (HCP) and Provincial Medical Genetics Program (PMGP)) between 2015-2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI:1.04,1.10); while this likelihood had an immediate 87% drop when the change occurred (OR:0.13; 95% CI: 0.06,0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay. This article is protected by copyright. All rights reserved.

Implementing context-appropriate neonatal and paediatric advanced life support management interventions has increasingly been recommended as one of the approaches to reduce under-five mortality in resource-constrained settings like Rwanda. One such intervention is ETAT+, which stands for Emergency Triage, Assessment and Treatment plus Admission care for severely ill newborns and children. In 2013, ETAT+ was implemented in Rwandan district hospitals. We evaluated the impact of the ETAT+ intervention on newborn and child health outcomes. We used monthly time-series data from the DHIS2-enabled Rwanda Health Management Information System from 2012 to 2016 to examine neonatal and paediatric hospital mortality rates. Each hospital contributed data for 12 and 36 months before and after ETAT+ implementation, respectively. Using controlled interrupted time-series analysis and segmented regression model, we estimated longitudinal changes in neonatal and paediatric hospital mortality rates in intervention hospitals relative to matched concurrent control hospitals. We also studied changes in case fatality rate specifically for ETAT+-targeted conditions. Our study cohort consisted of 7 intervention hospitals and 14 matched control hospitals contributing 142 424 neonatal and paediatric hospital admissions. After controlling for secular trends and autocorrelations, we found that the ETAT+ implementation had no statistically significant impact on the rate of all-cause neonatal and paediatric hospital mortality in intervention hospitals relative to control hospitals. However, the case fatality rate for ETAT+-targeted neonatal conditions decreased immediately following implementation by 5% (95% confidence interval: −9.25, −0.77) and over time by 0.8% monthly (95% confidence interval: −1.36, −0.25) in intervention hospitals compared with control hospitals. Case fatality rate for ETAT+-targeted paediatric conditions did not decrease following the ETAT+ implementation. While ETAT+ focuses on improving the quality of hospital care for both newborns and children, we only found an impact on neonatal hospital mortality for ETAT+-targeted conditions that should be interpreted with caution given the relatively short pre-intervention period and potential regression to the mean.

Ongoing rapid growth in the need for genetic services has the potential to severely strain the capacity of the clinical genetics workforce to deliver this care. Unfortunately, assessments of the scale of this health policy challenge and potential solutions are hampered by the lack of a consolidated evidence base on the growth in genetic service utilization. To enable health policy research and strategic planning by health systems in this area, we conducted a scoping review of the literature on the utilization and uptake of clinical genetics services in high-income countries published between 2010 and 2018. One-hundred-and-ninety-five unique studies were included in the review. Most focused on cancer (85/195; 44%) and prenatal care (50/195; 26%), which are consistently the two areas with the greatest volume of genetic service utilization in both the United States and other high-income countries. Utilization and uptake rates varied considerably and were influenced by contextual factors including health system characteristics, provider knowledge, and patient preferences. Moreover, growth in genetic service utilization appears to be driven to a significant degree by technological advances and the integration of new tests into clinical care. Our review highlights both the policy challenge posed by the rapid growth in the utilization of genetic services and the variability in this trend across clinical indications and health systems.

The aim of this review was to summarize all available evidence on the cost effectiveness of potentially curative gene therapies and identify challenges that economic evaluations face in this area. We conducted a systematic review of four databases (PubMed/MEDLINE, Embase, CINAHL, EconLit) and grey literature sources. We conducted the search on August 23, 2019 and updated it on November 26, 2020. We included all English, French and Spanish language studies that addressed a gene therapy that had received regulatory approval or had entered a phase III trial, and also reported on costs related to the therapy. Critical appraisal was conducted to assess quality of reporting in included studies. Fifty-six studies were identified. Of the 42 full economic evaluations, 71% (n = 30) evaluated chimeric antigen receptor T-cell therapies, most used either a Markov model (n = 17, 40%) and/or a partitioned survival model (n = 17, 40%), and 76% (n = 32) adopted a public or private payer perspective. The model characteristics with the greatest impact on cost effectiveness included assumptions about the efficacy of the treatment and the comparators used. All gene therapies in this review were shown to be more effective than their comparators, although due to high costs not all were considered cost effective at standard cost-effectiveness thresholds. Despite their high cost, some gene therapies have the potential to dominate the alternatives in conditions with high mortality/disability. The choice of comparator and assumptions regarding long-term effectiveness had substantial impacts on cost-effectiveness estimates and need to be carefully considered. Both the quality of inputs and the quality of reporting were highly variable.

Contemporary management of chronic obstructive pulmonary disease (COPD) relies on exacerbation history to risk-stratify patients for future exacerbations. Multivariable prediction models can improve the performance of risk stratification. However, the clinical utility of risk stratification can vary from one population to another.How do two validated exacerbation risk prediction models (ACCEPT and Bertens) compared to exacerbation history alone perform in different patient populations?We used data from three clinical studies representing populations at different levels of moderate/severe exacerbation risk: the Study to Understand Mortality and Morbidity in COPD (SUMMIT, N=2,421, annual risk=0.22), the Long-term Oxygen Treatment Trial (LOTT, N=595, annual risk=0.38), and Towards a Revolution in COPD Health (TORCH, N=1,091, annual risk=0.52). We compared the area under the curve (AUC) and net benefit (measure of clinical utility) among three risk stratification algorithms for predicting exacerbations in the next 12 months. We also evaluated the effect of model recalibration on clinical utility.Compared to exacerbation history, ACCEPT had better performance in all three samples (ΔAUC 0.08, 0.07, and 0.10 - all P-values ≤0.001). Bertens had better performance compared to exacerbation history in SUMMIT and TORCH (ΔAUC 0.10 and 0.05 - P-values0.001), but not in LOTT. No algorithm was superior in clinical utility across all samples. Before recalibration, Bertens generally outperformed the other algorithms in low-risk settings while ACCEPT outperformed others in high-risk settings. All three algorithms had the risk of harm (providing lower net benefit than not using any risk stratification). After recalibration, risk of harm was substantially mitigated for both prediction models.Exacerbation history alone is unlikely to provide clinical utility for predicting COPD exacerbations in all settings and could be associated with a risk of harm. Prediction models have superior predictive performance but require setting-specific recalibration to confer higher clinical utility.

Background: Multiple Sclerosis (MS) affects people in their most productive years of life. Consequently, MS can substantially affect employment and work-related outcomes. Objectives: This study characterizes productivity loss and employment status of people with multiple sclerosis (pwMS) and investigates associated factors. Methods: We used baseline data collected as part of the Canadian Prospective Cohort Study to Understand Progression in Multiple Sclerosis (CanProCo). Using the Valuation of Lost Productivity questionnaire, we measured MS-related paid work productivity loss for those employed, productivity losses incurred by those unemployed (i.e. lost employment time), and unpaid work productivity losses for all. A set of sociodemographic, disease, and performance-related factors were investigated using a two-part regression model for productivity loss and a multinomial logistic model for employment status. Results: From the cohort of 888 pwMS enrolled at baseline (mostly showing mild to moderate disability), 75% were employed, and of those unemployed, 69% attributed their unemployment to health-related issues. Total productivity loss over a 3-month period averaged 64 and 395 hours for those employed and unemployed, respectively. Some factors that affected productivity loss and employment status included use of disease-modifying therapies, fatigue, and performance indicators such as cognitive processing speed. Conclusion: Productivity loss experienced by employed and unemployed pwMS is substantial. Targeting the identified modifiable factors is likely to improve work productivity and permanence of MS patients in the workforce.

The use of observational data to assess drug effectiveness and safety can provide relevant information, much of which may not be feasible to obtain through randomized clinical trials. Because observational studies provide critical drug safety and effectiveness information that influences drug policy and prescribing practices, transparent, consistent, and accurate reporting of these studies is critical.We provide recommendations to extend existing reporting guidelines, covering the main components of primary research studies (methods, results, discussion).Our recommendations include extending drug safety and effectiveness guidelines to include explicit checklist items on: study registration, causal diagrams, rationale for measures of effect, comprehensive assessment of bias, comprehensive data cleaning steps, drug equivalents, subject-level drug data visualization, sex and gender-based analyses and results, patient-oriented outcomes, and patient involvement in research.

Asthma hospitalizations declined rapidly in many parts of the world, including Canada, in the 1990s and early 2000s.To examine whether the declining trend of asthma hospitalizations persisted in recent years in Canada.Using the Canadian comprehensive nationwide hospitalization data (2002-2017), we identified hospital admissions with the main International Classification of Diseases codes for asthma. We analyzed sex-specific age-standardized trends in annual hospitalization rates among pediatric (amp;lt; 19 years) and adult (19+ years) patients. We used change-point analysis to evaluate any substantial changes in the trends in the sex-age groups.There were 254,672 asthma-related hospital admissions (59% pediatric, 50% female) during the study period. Among children, age-adjusted annual rates per 100,000 decreased by 55% in females (152-69) and by 60% in males (270-108) from 2002 to 2017. Among adults, the rates decreased by 59% in both sexes (females: 61-25; males: 27-11). Change-point analysis indicated a substantial plateauing of the annual rate in both pediatric (from -15.3 [females] and -25.8 [males] before 2010 to -0.6 [females] and -0.8 [males] after 2010) and adult (from -5.4 [females] and -2.6 [males] before 2008 to -0.6 [females] and -0.2 [males] after 2008) groups.After a substantial decline in hospital admissions for acute asthma, there has been minimal further decline since 2010 for children and 2008 for adults. In addition to adhering to the contemporary standards of asthma care, novel, disruptive strategies are likely needed to further reduce the burden of asthma.

New Zealand’s near static healthcare budget limits access to expensive medications including those for rare conditions. As such, it is necessary to know the public’s priority for values in the drug funding decision-making process. The objectives of this study were to measure the relative societal importance of values of New Zealanders in informing drug funding decisions and to determine how New Zealanders trade off funding in various scenarios between common and rare diseases. An online survey was conducted between 17 April and 17 May, 2019 on a sample of 500 New Zealanders aged ≥ 18 years. Participants ranked 13 values using an analytical hierarchy process. Participants were then presented with different trade-off scenarios to measure their attitudes towards funding drugs for common and rare diseases. The values ranked in the top five by most were potential effect on quality of life (71.8%), ability of the drug to work (57.6%), severity (57.6%), safety (57%), and potential to extend life (56%). Adherence and rarity held the lowest and second lowest ranking. Most believe that resources should be allocated towards drugs that have been proven to work and have the greatest health benefits. In trade-offs between access to an expensive drug therapy for a rare disease with uncertain benefits or receive a fixed cash payment, the overwhelming consensus was to receive the cash payment. New Zealanders ultimately value drug-related factors (e.g. quality of life and efficacy) and disease-related factors (e.g. severity of disease and equity) the most but did not value disease rarity.

The value of early detection and treatment of chronic obstructive pulmonary disease (COPD) is currently unknown. We assessed the cost effectiveness of primary care-based case detection strategies for COPD. A previously validated discrete event simulation model of the general population of COPD patients in Canada was used to assess the cost effectiveness of 16 case detection strategies. In these strategies, eligible patients (based on age, smoking history, or symptoms) received the COPD Diagnostic Questionnaire (CDQ) or screening spirometry, at 3- or 5-year intervals, during routine visits to a primary care physician. Newly diagnosed patients received treatment for smoking cessation and guideline-based inhaler pharmacotherapy. Analyses were conducted over a 20-year time horizon from the healthcare payer perspective. Costs are in 2019 Canadian dollars ($). Key treatment parameters were varied in one-way sensitivity analysis. Compared to no case detection, all 16 case detection scenarios had an incremental cost-effectiveness ratio (ICER) below $50,000/QALY gained. In the most efficient scenario, all patients aged ≥ 40 years received the CDQ at 3-year intervals. This scenario was associated with an incremental cost of $287 and incremental effectiveness of 0.015 QALYs per eligible patient over the 20-year time horizon, resulting in an ICER of $19,632/QALY compared to no case detection. Results were most sensitive to the impact of treatment on the symptoms of newly diagnosed patients. Primary care-based case detection programs for COPD are likely to be cost effective if there is adherence to best-practice recommendations for treatment, which can alleviate symptoms in newly diagnosed patients.

Background Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. Methods We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. Results The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73–1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77–0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96–0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75–1.10). Conclusions The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Background Medication management (MM) refers to all clinical activities that a pharmacist performs to ensure safe and effective medication therapy for patients. Objective To characterize pharmacist-driven MM services via retrospective analysis of real-world data collected in a community pharmacy in British Columbia (BC), Canada. Methods This was a retrospective longitudinal study from January 2014–December 2015. Patient demographics, clinical problems, identified drug-related problems (DTPs), and pharmacists' interventions were summarized using descriptive statistics. The relationship between DTPs and the clinical conditions, as well as DTPs and the interventions, were analyzed. Other outcomes included: the relationship between patients’ age and visit time with the number of DTPs; the number of clinical conditions; and the number of interventions. Results 1,572 patients received MM (mean visit time = 29.1 min). 2,133 DTPs were identified, which resulted in 7176 recommended interventions. The clinical problems most frequently encountered were cardiovascular (20%), and mental (15.7%). The most frequently identified DTP was “needs additional therapy” (61.8%), while the most frequently initiated or recommended interventions were education (43.4%), and changing therapy (21.6%). Elderly patients with multiple comorbidities had more DTPs and required more interventions and even when no DTPs were identified, some patients still received counselling and education in these visits. Conclusion Using real-world data, this research demonstrated that patients benefit from identification and resolution of DTPs through pharmacists-driven MM programs.

This study describes the cost trajectory of the standard diagnostic care pathway for children with suspected genetic disorders in British Columbia, Canada. Average annual per-patient costs were estimated using medical records review and a caregiver survey for a cohort of 498 children referred to BC Children’s and Women’s Hospitals (CW exome and genome sequencing) to 500 families of children with suspected genetic disorders. Direct costs peaked in the first year of patients’ diagnostic odyssey, with an average of C$2257 per patient (95% confidence interval [CI] C$2074, C$2441) for diagnostic testing and C$631 (95% CI C$543, C$727) for specialist consultations at C&W. In subsequent years, direct costs accrued at a constant rate, with an estimated annual per-patient cost of C$511 (95% CI C$473, C$551) for diagnostic testing and C$334 (95% CI C$295, C$369) for consultations at C&W. Travel costs and caregiver productivity loss associated with attending diagnosis-related physician appointments averaged C$1907/family/year. The continuing long-term accrual of costs by undiagnosed patients suggests that economic evaluations of diagnostic GWS services should use longer time horizons than have typically been used.

This study aimed to compare downstream utilization of medical services among critically ill infants admitted to intensive care units who received rapid exome sequencing (ES) and those who followed alternative diagnostic testing pathways.Using propensity score-weighted regression models including sex, age at admission, and severity indicators, we compared a group of 47 infants who underwent rapid ES with a group of 211 infants who did not receive rapid ES. Utilization and cost indicators were compared between cohorts using negative binomial models for utilization and two-part models for costs.After controlling for patients' sociodemographic and clinical characteristics, we found no statistically significant difference in outpatient visits, hospitalizations, intensive care unit or total length of stay, or length of stay-associated costs between the cohorts at 12- or 26-month follow-up. Similarly, there was no evidence of higher utilization or costs by the ES group when infants who died were removed from the analysis.When examining utilization during and beyond the diagnostic trajectory, there is no evidence that ES changes frequency of outpatient visits or use of in-hospital resources in critically ill infants with suspected genetic disorders.

Background Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). Although there are a handful of disease-modifying treatments approved for use in progressive phenotypes of MS, there are no treatments that substantially modify the course of clinical progression in MS. Characterizing the determinants of clinical progression can inform the development of novel therapeutic agents and treatment approaches that target progression in MS, which is one of the greatest unmet needs in clinical practice. Canada, having one of the world’s highest rates of MS and a publicly-funded health care system, represents an optimal country to achieve in-depth analysis of progression. Accordingly, the overarching aim of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) is to evaluate a wide spectrum of factors associated with the clinical onset and rate of disease progression in MS, and to describe how these factors relate to one another to influence progression. Methods CanProCo is a prospective, observational cohort study with investigators specializing in epidemiology, neuroimaging, neuroimmunology, health services research and health economics. CanProCo’s study design was approved by an international review panel, comprised of content experts and key stakeholders. One thousand individuals with radiologically-isolated syndrome, relapsing-remitting MS, and primary-progressive MS within 10–15 years of disease onset will be recruited from 5 academic MS centres in Canada. Participants will undergo detailed clinical evaluation annually over 5 years (including advanced, app-based clinical data collection). In a subset of participants within 5–10 years of disease onset (n = 500), blood, cerebrospinal fluid, and research MRIs will be collected allowing an integrated, in-depth evaluation of factors contributing to progression in MS from multiple perspectives. Factors of interest range from biological measures (e.g. single-cell RNA-sequencing), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician-assessed, health-system based), and micro and macro-environmental factors. Discussion Halting the progression of MS remains a fundamental need to improve the lives of people living with MS. Achieving this requires leveraging transdisciplinary approaches to better characterize why clinical progression occurs. CanProCo is a pioneering multi-dimensional cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions.

Background Medication taking is a dynamic behaviour that changes over time. Conventional adherence summary measures (e.g. proportion days covered) used in the OAC adherence studies conducted so far, however, are insensitive to the fluid nature of adherence. For example, identical PDC values can be calculated for patients with initial good adherence followed by poor adherence, and for those with periodic non-adherence throughout the course of therapy. Purpose The objective of this study was to characterize atrial fibrillation (AF) patients' long-term unique oral anticoagulant (OAC) adherence trajectories. Methods Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996–2019), incident adult cases of AF were identified. Only patients who had prescription refill data available for five years were included in the analysis. The primary measure of OAC adherence was the proportion of days covered (PDC) over consecutive 90-day rolling windows. We modelled continuous 90-day PDC values over time. The time variable was number of years since OAC initiation. Group-Based Trajectory Modelling (GBTM) was used to identify patients' unique longitudinal adherence trajectories. To determine the best model, a relative comparison was done between models using Bayesian information criteria (BIC), and the Akaike information criterion (AIC). Results The study cohort was 19,749 AF patients [mean age 70.6y (SD 10.64), 56% male, mean CHA2DS2-VASc score 2.77 (SD 1.39]. The model that best fit our data identified four distinct OAC adherence trajectories (Figure). These were “consistent good adherence” (n=14,631 patients, 74.1% of the cohort), “rapid decline and discontinuation” (n=2327, 11.8%), “rapid decline with recovery” (n=1973, 9.99%), and “slow decline and discontinuation” (n=819, 4.2%). Our results show that there is heterogeneity among non-adherers. PDC dropped significantly in the first year after therapy initiation for those with “rapid decline and discontinuation” trajectory. Patients exhibiting “rapid decline with recovery” also displayed a rapid decline in adherence in the first year but showed improvements around the third year. Those in the “slow decline and discontinuation” trajectory displayed slow decline in adherence over first three years which eventually led to permanent discontinuation of therapy. Conclusion In this retrospective study we distinguished between the different kinds of non-adherence in terms of timing and rate. While a majority of our cohort adhered to their medications, we identified three unique trajectories displaying declining adherence over time at varying rates. Our results emphasize the importance of early intervention and have direct implications for improving the design of adherence interventions. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research grant

Background A recent systematic review highlighted significant gaps in the evidence on atrial fibrillation (AF) patients' adherence to oral anticoagulants (OAC). Current evidence suffers from short follow-up times, focuses on the first OAC and does not take switching into account. There is also lack of observational data on adherence to warfarin due to its varying dose that complicates the calculations. As such there is lack of evidence on comparative adherence between VKAs and DOACs and whether the convenience of DOACs translates into better adherence in AF patients. Purpose Our objective was to measure AF patients' long-term OAC adherence and compare the impact of taking direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) on adherence, while accounting for switching. Methods Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996–2019), incident adult cases of AF were identified. The primary measure of adherence was proportion of days covered (PDC). Consecutive rolling 90-day windows were created for each patient starting from their first OAC prescription fill date until the end of their follow-up. The PDC for each 90-day rolling window was calculated and averaged to yield mean adherence over the follow-up period for each patient. Permanent medication discontinuation resulted in a PDC of 0 for all subsequent rolling windows after their supply ran out. As such, both poor execution and non-persistence were measured simultaneously. The association between drug class and adherence was assessed using generalized mixed effect linear regression models with drug class treated as time-varying covariate to account for switching. Results The study cohort was 30,264 AF patients [mean age 72.2 years (SD11.0), 44.6% female, mean CHA2DS2-VASc 2.94 (SD1.4)] with mean follow-up of 7.7 (SD 4.8) years. The mean PDC was 0.71 (SD 0.27) with 51% of the cohort having mean PDC values below the conventional threshold of adherence (PDC Conclusion AF patients' OAC adherence was below the conventional threshold of 0.8, and dropped over time, particularly in the first two years. Drug class had no clinically meaningful impact on medication adherence. Our study highlights the need for effective adherence interventions particularly early in OAC therapy. Our findings also emphasizes that prescribers should not assume inherently better adherence for DOACs and should instead choose OAC in conversation with the patient and in accordance with their values and preferences. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research grant

Genomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. We examine whether the current evidence base reflects public tolerance for uncertainty for genomics to diagnose rare childhood genetic disease. We conducted focus groups with general population parents in Vancouver, Canada, and Oxford, United Kingdom, to discuss expectations and concerns related to genomic testing to diagnose rare childhood genetic disease. Applying a purposive sampling technique, recruitment continued until thematic saturation was reached. Transcripts were analysed using thematic analysis. Thirty-three parents participated across four focus groups. Participants valued causal diagnoses alongside management strategies to improve patient health and wellbeing. Further, participants valued expanding the evidence base to reduce evidentiary uncertainty while ensuring security of information. Willingness to pay out of pocket for testing reflected perceived familial health benefit. Diagnostic yield fails to fully capture valued outcomes, and efforts to resolve uncertainty better reflect public priorities. Evaluations of genomic testing that fully integrate valued endpoints are necessary to ensure consistency with best practices and public willingness to accept the uncertain familial benefit.

Objective To demonstrate the landscape of model-based economic studies in asthma and highlight where there is room for improvement in the design and reporting of studies. Design A systematic review of the methodologies of model-based, cost-effectiveness analyses of asthma-related interventions was conducted. Models were evaluated for adherence to best-practice modeling and reporting guidelines and assumptions about the natural history of asthma. Methods A systematic search of English articles was performed in MEDLINE, EMBASE, and citations within reviewed articles. Studies were summarized and evaluated based on their adherence to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). We also studied the underlying assumptions about disease progression, heterogeneity in disease course, comorbidity, and treatment effects. Results Forty-five models of asthma were included (33 Markov models, 10 decision trees, 2 closed-form equations). Novel biological treatments were evaluated in 12 studies. Some of the CHEERS’ reporting recommendations were not satisfied, especially for models published in clinical journals. This was particularly the case for the choice of the modeling framework and reporting on heterogeneity. Only 13 studies considered any subgroups, and 2 explicitly considered the impact of comorbidities. Adherence to CHEERS requirements and the quality of models generally improved over time. Conclusion It would be difficult to replicate the findings of contemporary model-based evaluations of asthma-related interventions given that only a minority of studies reported the essential parameters of their studies. Current asthma models generally lack consideration of disease heterogeneity and do not seem to be ready for evaluation of precision medicine technologies.

Background: Multiple sclerosis (MS) typically affects young adults during their primary productive years. We assessed the magnitude of, and factors associated with, employment status and informal care in people with MS in Canada. Methods: Data were compiled from the nationally representative cross-sectional Survey on Living with Neurological Conditions in Canada (SLNCC), which included adolescents and adults (age ≥15 years). Employment status was categorized as currently working or not working. The frequency of informal care that people with MS received was categorized as none, less than daily, or daily. Logistic regression analyses were undertaken to identify factors associated with employment status and informal care requirements in people with MS. Results: Of 4409 SLNCC respondents, 631 had MS, of whom 530 were included in the analysis. Of 358 respondents aged 18 to 65 years, 47.8% were not working because of MS; 44.0% reported receiving informal care, with more than half requiring daily care. For caregivers' employment, 15.5% reduced work and 8.2% stopped working because of caregiving. Greater feelings of stigmatization were associated with not working (adjusted odds ratio, 7.42 [95% CI, 2.59–21.28]) and greater informal care (adjusted odds ratio, 3.83 [95% CI, 1.84–7.96]), adjusting for sex, age, education, health-related quality of life, time since MS diagnosis, and comorbidity. Conclusions: People who feel stigmatized because of their MS are more likely to be unemployed and to require more informal care. Further research is needed to understand the temporal nature of the association between stigma and employment, productivity loss, and informal care.

Background Decision makers are facing growing challenges in prioritizing drugs for reimbursement because of soaring drug costs and increasing pressures on financial resources. In addition to cost and effectiveness, payers are using other values to dictate which drugs are prioritized for funding, yet there are limited data on the Canadian public’s priorities. Objectives To measure the relative societal importance of values considered most relevant in informing drug reimbursement decisions in a representative sample of Canadians. Methods An online survey of 2539 Canadians aged 19 years and older was performed in which 13 values used in drug funding prioritization were ranked and then weighted using an analytic hierarchy process. Results Canadians value safe and efficacious drugs that have certainty of evidence. The values ranked in the top 5 by most of our subjects were potential effect on quality of life (65.4%), severity of the disease (62.6%), ability of drug to work (61.1%), safety (60.5%), and potential to extend life (49.4%). Values related to patient or disease characteristics such as rarity, socioeconomic status, and health and lifestyle choices held the lowest rankings and weights. Conclusions Canadians value, above all, treatment-related factors (eg, efficacy and safety) and disease-related factors (eg, severity and equity). Decision makers are currently using additional justifications to prioritize drugs for reimbursement, such as rarity and unmet need, which were not found to be highly valued by Canadians. Decision makers should integrate the public’s values into a Canadian reimbursement framework for prioritization of drugs competing for limited funds.

Stroke prevention therapy decisions for patients with atrial fibrillation (AF) are complex and require trade-offs, but few validated patient decision aids (PDAs) are available to facilitate shared decision making.To evaluate the effects of a novel PDA on decision-making parameters for AF patients choosing stroke prevention therapy.We developed an evidence-based individualized online AF PDA for stroke prevention therapy and evaluated it in a prospective observational pilot study. The primary outcome was decisional conflict. Secondary outcomes were knowledge, usability/acceptability, patient preferences, effects on therapy choices, and participant feedback.37 participants completed the PDA. The PDA could be completed independently and was well accepted. It significantly decreased the mean decisional conflict score ( P0.001) and all its subscales and increased participant AF knowledge ( P = 0.02). 76% of participants indicated that their individualized therapy attribute ranking was congruent with their values. The PDA-generated best-match therapy was chosen by 70% of participants in decision 1 (no therapy, aspirin, or oral anticoagulant), and 17% for decision 2 (choice of anticoagulant). Among AF patients, 60% chose a different drug than that currently prescribed to them. Conclusion and Relevance: Our PDA was effective for reducing decisional conflict, increasing patient knowledge, eliciting patients' values, and presenting therapy options that aligned with patients' values and preferences. Using the PDA revealed that many patients have therapy preferences different from their currently prescribed treatment. The PDA is a practical and potentially valuable tool to facilitate decision making about stroke prevention therapy for AF.

Full coverage of the cost of clinical genetic testing is not always available through public or private insurance programs, or a public healthcare system. Consequently, some patients may be faced with the decision of whether to finance testing out-of-pocket (OOP), meet OOP expenses required by their insurer, or not proceed with testing. A scoping review was conducted to identify literature associated with patient OOP and private pay in clinical genetic testing. Seven databases (EMBASE, MEDLINE, CINAHL, PsychINFO, PAIS, the Cochrane Database of Systematic Reviews, and the JBI Evidence-Based Practice database) were searched, resulting in 83 unique publications included in the review. The presented evidence includes a descriptive analysis, followed by a narrative account of the extracted data. Results were divided into four groups according to clinical indication: (1) hereditary breast and ovarian cancer, (2) other hereditary cancers, (3) prenatal testing, (4) other clinical indications. The majority of studies focused on hereditary cancer and prenatal genetic testing. Overall trends indicated that OOP costs have fallen and payer coverage has improved, but OOP expenses continue to present a barrier to patients who do not qualify for full coverage.

Genomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. We examine whether the current evidence base reflects public tolerance for uncertainty for genomics to diagnose rare childhood genetic disease. We conducted focus groups with general population parents in Vancouver, Canada, and Oxford, United Kingdom, to discuss expectations and concerns related to genomic testing to diagnose rare childhood genetic disease. Applying a purposive sampling technique, recruitment continued until thematic saturation was reached. Transcripts were analysed using thematic analysis. Thirty-three parents participated across four focus groups. Participants valued causal diagnoses alongside management strategies to improve patient health and wellbeing. Further, participants valued expanding the evidence base to reduce evidentiary uncertainty while ensuring security of information. Willingness to pay out of pocket for testing reflected perceived familial health benefit. Diagnostic yield fails to fully capture valued outcomes, and efforts to resolve uncertainty better reflect public priorities. Evaluations of genomic testing that fully integrate valued endpoints are necessary to ensure consistency with best practices and public willingness to accept the uncertain familial benefit.

BACKGROUND Studies measuring OAC adherence in AF patients have suffered from short follow-up times, inability to account for frequent medication switches and have excluded warfarin. Our objective was to compare AF patients' long-term adherence between OACs and identify the impact of taking direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) on adherence, while accounting for switching. METHODS AND RESULTS Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996-2019), incident adult cases of AF were identified. Primary measure of adherence was proportion days covered (PDC). Consecutive rolling windows of 90 day in length were created for each patient starting from their first OAC prescription fill date until the end of their follow-up time. PDC for each of the 90-day-long rolling windows were calculated. If a person permanently discontinued their medication, they were given a PDC of 0 for all subsequent rolling windows after their last supply ran out, until the end of their follow-up period. As such, both poor execution and non-persistence were measured simultaneously. Patient's average adherence over follow-up was obtained by calculating the mean of PDC values of all their windows during follow-up. Changes in adherence over time and the association between drug class and adherence were assessed using generalized mixed effect linear regression model with both adherence and drug class treated as time-varying covariates. Study sample comprised of 30,264 AF patients [mean age: 72.2(SD11.0), 44.6% Female] with mean follow-up of 7.7(4.8) years. A majority were initiated on warfarin (69.7%), with mean CHA2DS2-VASc score of 2.94 (SD1.4). Mean PDC for our cohort was 0.71(SD0.27) with 51% considered non-adherent (PDC CONCLUSION Adherence to OACs in patients with AF was well below the conventional threshold of 80%, with less than half of the patients taking these medications as prescribed. Adherence dropped over time, particularly in the first two years after therapy initiation. Switching was common. Drug class had no meaningful impact on medication adherence.

Warfarin’s complex dosing is a significant barrier to measurement of its exposure in observational studies using population databases. Using population-based administrative data (1996–2019) from British Columbia, Canada, we developed a method based on statistical modeling (Random Effects Warfarin Days’ Supply (REWarDS)) that involves fitting a random-effects linear regression model to patients’ cumulative dosage over time for estimation of warfarin exposure. Model parameters included a minimal universally available set of variables from prescription records for estimation of patients’ individualized average daily doses of warfarin. REWarDS estimates were validated against a reference standard (manual calculation of the daily dose using the free-text administration instructions entered by the dispensing pharmacist) and compared with alternative methods (fixed window, fixed tablet, defined daily dose, and reverse wait time distribution) using Pearson’s correlation coefficient (r), the intraclass correlation coefficient, and the root mean squared error. REWarDS-estimated days’ supply showed strong correlation and agreement with the reference standard (r = 0.90 (95% confidence interval (CI): 0.90, 0.90); intraclass correlation coefficient = 0.95 (95% CI: 0.94, 0.95); root mean squared error = 8.24 days) and performed better than all of the alternative methods. REWarDS-estimated days’ supply was valid and more accurate than estimates from all other available methods. REWarDS is expected to confer optimal precision in studies measuring warfarin exposure using administrative data.

Introduction Genome-wide sequencing (exome or whole genome) is transforming the care and management of paediatric patients with a rare disease because of its diagnostic capabilities. Genome-wide sequencing is most effective when both parents and the child are sequenced as a trio. Genetic counselling is recommended for all families considering genome-wide sequencing. Although telehealth is well established in genetic counselling for hereditary cancer and prenatal genetics, its use with genome-wide sequencing has not been well studied. The CAUSES Clinic at BC Children’s and Women’s Hospitals was a translational paediatric trio-based genome-wide sequencing initiative. Pre-test genetic counselling via telehealth (at a clinical site near the family’s residence) was offered to families who had been previously evaluated by a clinical geneticist. We report on the first 300 families seen in the CAUSES clinic and compare health services implementation issues of families seen via telehealth versus on-site. Methods Demographics, cost to families (travel and time), time to first appointment, complete trio sample accrual and diagnostic rates were studied. Results Of the 300 patients, 58 (19%) were seen via telehealth and 242 (81%) were seen on-site for pre-test counselling. The mean time to completion of accrual of trio samples in the telehealth group was 56.3 (standard deviation ±87.3) days versus 18.9 (standard deviation ±62.4) days in the onsite group ( p −16). The mean per-family estimated actual or potential travel/time cost savings were greater in the telehealth group (Can$987; standard deviation = Can$1151) than for those seen on-site (Can$305; standard deviation = Can$589) ( p = 0.0004). Conclusions Telehealth allowed for access to genome-wide sequencing for families in remote communities and for them to avoid significant travel and time costs; however, there was a significant delay to accrual of the complete trio samples in the telehealth group, impacting on time of result reporting and delaying diagnoses for families for whom genome-wide sequencing was diagnostic.

Background: Oral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort.Methods: We used administrative health databases of British Columbia, Canada (2000–2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression.Results: 21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (pConclusions: This population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.