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Objective To highlight progress in facilitating and supporting pan-Canadian data analysis research that is supported by a central coordinating center. This process will be illustrated with the use of a recently completed project that has been supported using data from Alberta, British Columbia, and Ontario. Approach The project represents a significant endeavor within the central coordinating center, as it necessitates coordination for data access, data importation and analytical support across three provinces. The focus will be on the administrative processes refined to support collaborative research endeavors. While specific project details will remain undisclosed, procedural enhancements within the central coordinating center framework will be highlighted. Key discussion points include standardized protocols for data access, collaborative efforts to streamline data importation, and facilitation of analytical support across jurisdictions. The type of cross-jurisdictional analytic support will as well be highlighted; data variables harmonization and sharing of data algorithms cohorts across the participating provincial data centers in support of the meta-analysis. Results The successful completion of the final data analysis underscores the effectiveness of a unified data access coordination center for researchers seeking multi-regional health data in Canada. By highlighting advancements enabled by the central coordinating center and provincial data centers, this submission aims to inform researchers about the current landscape of pan-Canadian research and foster opportunities for future collaboration. Implications Sharing insights and lessons from this project emphasizes the advancements facilitated by the central coordinating center and provincial data centers, informing researchers about the potential of pan-Canadian research, and encouraging future collaborative endeavors.

Objective To highlight the partnership between the Canadian Partnership for Tomorrow’s Health (CanPath) and Health Data Research Network (HDRN Canada), which enables researchers to link CanPath’s health and lifestyle survey data to health records and related data across multiple regions. Background CanPath is a population health study of over 350,000 Canadians from seven regional cohorts across all ten provinces, making it one of the world's largest population cohorts. HDRN Canada is a network of member organizations, including provincial, territorial, and pan-Canadian data centres. Approach This partnership leveraged collective expertise and resources to facilitate the linkage of CanPath’s harmonized data to multi-regional health and health-related administrative data held at HDRN Canada’ s data centres. Researchers can access these data for multi-regional projects through HDRN Canada’s Data Access Support Hub, which provides a single access portal. Results Researchers were able to successfully link CanPath’s survey data to provincial administrative health data. The collaboration’s streamlined process for data access enhances efficiency and facilitates pan-Canadian population health research. Conclusion This collaboration demonstrates the feasibility and value of linking population health datasets while demonstrating the challenges and opportunities associated with accessing national administrative health data within a federated health data system. Implications The partnership between CanPath and HDRN Canada has significant implications for advancing population health research in Canada. By providing researchers with access to linked data from diverse sources, the partnership enables comprehensive investigations into health determinants, disease patterns, and clinical outcomes. This enhances the scope and depth of population health research in Canada, thereby leading to a better understanding of the most pressing health challenges.

IntroductionAlthough colorectal cancer (CRC) screening program is proven to reduce CRC incidence and mortality, understanding patterns and predictors of suboptimal adherence in screening program requires further investigation in Canada.MethodsWe used self-reported data from five regional cohorts of the Canadian Partnership for Tomorrow’s Health (CanPath), namely the BC Generations Project (BCGP), Alberta’s Tomorrow Project (ATP), the Ontario Health Study (OHS), Quebec’s CARTaGENE, and the Atlantic Partnership for Tomorrow’s Health Study (Atlantic PATH). We stratified participants into the following four risk categories: 1) age 50-74 years, 2) family history in a first-degree relative, 3) personal history of chronic inflammatory bowel disease and/or polyps, and 4) co-existence of personal risk and family history. Multivariable logistic regression was used to identify predictors of adherence to the screening guidelines.ResultsAdherence to CRC screening varied considerably between regions, ranging from 16.6% in CARTaGENE to 47.7% in OHS. Compared to the largest cohort OHS, the likelihood of non-adherence to CRC screening was significantly higher in BCGP (OR 1.15, 95% CI 1.11-1.19), the Atlantic PATH (OR 1.90, 95% CI 1.82-1.99) and CARTaGENE (OR 5.10, 95% CI 4.85-5.36). Low physical activity, current smoking, presence of personal risk, family history of CRC significantly reduced the likelihood of adherence to screening recommendations.Discussion/conclusionCompared to the national target of ≥ 60% for participation in CRC screening, adherence to regular CRC screening was suboptimal in this cohort of Canadians and varied by region. Further efforts are needed to identify the specific barriers to screening adherence in different provinces and across risk categories.

Abstract Background Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. Methods and results Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p

Objectives We will enrich the cancer research ecosystem in Canada through linking cancer registry and administrative health data to the Canadian Partnership for Tomorrow’s Health (CanPath) cohort and biobank. CanPath is Canada’s largest population health study, including 1% of the Canadian population, which seeks to investigate cancer development. Approach We are achieving record-level linkage of the CanPath harmonized dataset to provincial cancer registry data, and hospitalization and ambulatory care data from the Canadian Institutes of Health Information (CIHI). The CanPATH harmonized dataset includes comprehensive genetics, environment, lifestyle, and behaviour data. Our linkage activities will result in interprovincial data sharing, with centrally-held linked data, a first in Canadian history. We will demonstrate the CanPath-cancer registry-CIHI linkage potential by investigating the impact of the COVID-19 pandemic on healthcare utilization and outcomes among those with cancer. Results The linkage is ongoing and anticipated to be completed by September 2022. Linked data will be made available through the CanPath Data Safe Haven, a cloud-based solution that meets the legal requirements of the data sharing agreements and provincial privacy policies, and is accessible to researchers through secure access. The CanPath Data Safe Haven will be a federated data platform for Canadian researchers to access, analyze, and contribute research in a collaborative environment. By linking these datasets, this project will: address concerns related to accessibility of cancer data in Canada; bring more value to existing data; support an enhanced understanding of the impacts of cancer on marginalized populations; and create a more integrated approach to cancer data access and management. Conclusion CanPath will be the first program in Canadian history to combine the wealth of cohort resources with cancer registry and administrative health data in a central location at a national scale. We will provide a single point of access for researchers to conduct novel investigations into cancer development and outcomes.

Background: The intent of the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort is to understand the early determinants of subclinical cardiac and vascular disease and progression in adults selected from existing cohorts—the Canadian Partnership for Tomorrow’s Health, the Prospective Urban and Rural Evaluation (PURE) cohort, and the Montreal Heart Institute Biobank. We evaluated how well the CAHHM-Health Services Research (CAHHM-HSR) subcohort reflects the Canadian population. Methods: A cross-sectional design was used among a prospective cohort of community-dwelling adults aged 35-69 years who met the CAHHM inclusion criteria, and a cohort of adults aged 35-69 years who responded to the 2015 Canadian Community Health Survey-Rapid Response module. The INTERHEART risk score was calculated at the individual level with means and proportions reported at the overall and provincial level. Results: There are modest differences between CAHHM-HSR study participants and the 2015 Canadian Community Health Survey-Rapid Response respondents in age (56.3 vs 51.7 mean years), proportion of men (44.9% vs 49.3%), and mean INTERHEART risk score (9.7 vs 10.1). Larger differences were observed in postsecondary education (86.8% vs 70.2%), Chinese ethnicity (11.0% vs 3.3%), obesity (23.2% vs 29.3%), current smoker status (6.1% vs 18.4%), and having no cardiac testing (30.4% vs 55.9%). Conclusions: CAHHM-HSR participants are older, of higher socioeconomic status, and have a similar mean INTERHEART risk score, compared with participants in the Canadian Community Health Survey. Differing sampling strategies and missing data may explain some differences between the CAHHM-HSR cohort and Canadian community-dwelling adults and should be considered when using the CAHHM-HSR for scientific research. Résumé: Contexte: L’étude Alliance canadienne cœurs et cerveaux sains (CAHHM) vise à mieux comprendre les facteurs déterminants précoces et la progression de l’atteinte cardiovasculaire subclinique chez des adultes sélectionnés au sein de cohortes existantes – soit celles de l’étude menée par le Partenariat canadien pour la santé de demain, de l’étude PURE (Prospective Urban and Rural Evaluation) et de la biobanque de l’Institut de cardiologie de Montréal. Nous avons évalué la mesure dans laquelle la sous-cohorte du volet de recherche sur l’utilisation des services de santé de la CAHHM (CAHHM-HSR) représente la population canadienne. Méthodologie: Nous avons adopté une approche transversale pour étudier une cohorte prospective d’adultes vivant dans la communauté âgés de 35 à 69 ans et répondant aux critères d’inclusion de l’étude CAHHM, ainsi qu’une cohorte d’adultes âgés de 35 à 69 ans ayant participé au volet de réponse rapide de l’Enquête sur la santé dans les collectivités canadiennes (ESCC) de 2015. Le score de risque INTERHEART individuel des participants a été calculé à partir des moyennes et des proportions rapportées à l’échelle globale et à l’échelle provinciale. Résultats: Les différences entre les participants du volet CAHHM-HSR et ceux du volet de réponse rapide de l’ESCC de 2015 étaient minimes quant à l’âge (56,3 ans vs 51,7 ans en moyenne), à la proportion d’hommes (44,9 % vs 49,3 %) et au score de risque INTERHEART moyen (9,7 vs 10,1). On a toutefois noté des différences plus importantes en ce qui concerne les caractéristiques suivantes : éducation postsecondaire (86,8 % vs 70,2 %), origine ethnique chinoise (11,0 % vs 3,3 %), obésité (23,2 % vs 29,3 %), tabagisme actuel (6,1 % vs 18,4 %) et absence d’antécédents d’examen cardiaque (30,4 % vs 55,9 %). Conclusions: Les participants du volet CAHHM-HSR sont plus âgés et ont un statut socioéconomique plus élevé que ceux du volet de réponse rapide de l’ESCC, mais ont un score de risque INTERHEART moyen comparable. Les différences quant aux stratégies d’échantillonnage et des données manquantes pourraient expliquer certains des écarts observés entre la cohorte CAHHM-HSR et celle des adultes canadiens vivant dans la communauté; il conviendrait d’en tenir compte lorsqu’on utilise les données du volet CAHHM-HSR à des fins de recherche scientifique.

Introduction Alberta's Tomorrow Project (ATP) is the largest population-based prospective cohort study of cancer and chronic diseases in Alberta, Canada. The ATP cohort data were primarily self-reported by participants on lifestyle behaviors and disease risk factors at the enrollment, which lacks sufficient and accurate data on chronic disease diagnosis for longer-term follow-up. Objectives To characterize the occurrence rate and trend of chronic diseases in the ATP cohort by linking with administrative healthcare data. Methods A set of validated algorithms using ICD codes were applied to Alberta Health (AH) administrative data (October 2000-March 2018) linked to the ATP cohort to determine the prevalence and incidence of common chronic diseases. Results There were 52,770 ATP participants (51.2± 9.4 years old at enrollment and 63.7% females) linked to the AH data with average follow-up of 10.1± 4.4 years. In the ATP cohort, hypertension (18.5%), depression (18.1%), chronic pain (12.8%), osteoarthritis (10.1%) and cardiovascular diseases (8.7%) were the most prevalent chronic conditions. The incidence rates varied across diseases, with the highest rates for hypertension (22.1 per 1000 person-year), osteoarthritis (16.2 per 1000 person-year) and ischemic heart diseases (13.0 per 1000 person-year). All chronic conditions had increased prevalence over time (p

Introduction Pharmaceutical Information Network (PIN, 2008-now) is a provincial database collecting patients’ medication information in Alberta, Canada. Alberta Blue Cross (ABC), the largest health benefit provider in Alberta, has been managing pharmaceutical records for senior patients (65+ years) whose medications are covered by Alberta’s government-sponsored health benefit plan since 1970s. Objectives and Approach Over 96% of participants in Alberta’s Tomorrow Project (ATP), a province-wide cohort study of cancer and chronic diseases in Canada, consented to data linkage to healthcare databases. To cross-validate medication records in the two pharmaceutical databases in Alberta, individual-level data of ATP participants aged 65+ years were cross-linked between PIN and ABC databases (2008-2015) using Personal Health Numbers. Concordant and discordant records were identified by whether or not a specific record co-existed in the two databases. Concordance and discordance (discrepancy) rates, i.e. percentage of concordant or discordant records, were estimated by years and drug types. Results During 2008-2015, there were 1,116,176 records collected by PIN, 1,005,548 records collected by ABC, and a total of 1,218,191 records collected by both for 13,413 ATP participants. The average discrepancy rate between PIN and ABC was 25.8%, and the rate was significantly lower for drugs commonly prescribed for health conditions in seniors, including cardiovascular diseases (18.7% for statin), hypertension (18.9% for beta blockers, ace inhibitors and diuretics), diabetes (23.8% for glucose lower drugs), COPD (20.2% for inhalers) and stomach disorders (22.3% for H2 antagonists and proton pump inhibitors), compared to other drugs (34.4%). For insured drugs, using ABC as reference database, 88.6% of ABC records were concordant with (co-existing in) PIN. The concordance rate for insured drug use was improved by 10% over 2008-2015. Conclusion/Implications By cross-linking two pharmaceutical databases in Alberta for senior ATP participants, we found remarkable discrepancies in pharmaceutical records between PIN and ABC, although there was noticeable improvement over the years. The discrepancy rate between PIN and ABC was drug-specific and significantly lower for drugs commonly prescribed in senior patients.

Introduction Alberta’s Tomorrow Project (ATP) is a province-wide cohort study of cancer and chronic diseases in Canada. Approximately 55,000 Albertans aged 35-69 years with no history of cancer, other than non-melanoma skin cancer, had joined the ATP. Nearly all (>96%) ATP participants consented to data linkage to administrative healthcare databases. Objectives and Approach To validate chronic conditions self-reported by the ATP participants, individual-level data of a total of 52,851 ATP participants were linked to Alberta Health (AH) administrative datasets using Personal Health Number. Cases of chronic conditions, including diabetes, cardiovascular diseases and gastrointestinal disorders, were identified by algorithms for disease diagnosis using International Classification of Diseases (ICD) codes in administrative healthcare data. Cases were identified as “prevalent” if the index date of diagnosis was before or within 6 months of ATP enrollment date. Self-reported chronic conditions were validated by the cases identified as “prevalent” using the linked AH datasets. Results Among the ATP cohort, 804 participants self-reported ever being diagnosed with myocardial infarction (MI), 451 with stroke, 2,907 with diabetes, 566 with ulcerative colitis, 362 with Crohn’s disease and 112 with liver cirrhosis before or at the time of ATP enrollment. Using the linked AH administrative data, 339 participants were identified as prevalent cases with MI, 200 with stroke, 2,702 with diabetes, 208 with ulcerative colitis, 283 with Crohn’s disease and 55 with liver cirrhosis. The sensitivity and specificity of self-reporting having chronic conditions by the ATP participants were 71.1% and 97.0% for MI, 44.4% and 99.3% for stroke, 78.1% and 98.4% for diabetes, 73.6% and 99.2% for ulcerative colitis, 65.7% and 99.7% for Crohn’s disease and 50.9% and 99.8% for liver cirrhosis. Conclusion/Implications By linking with administrative healthcare data, we were able to validate the accuracy of self-reporting chronic conditions in ATP participants. The sensitivity of self-reporting was acceptable for MI, diabetes, ulcerative colitis and Crohn’s disease, but low for stroke and liver cirrhosis. The specificity was high for all chronic conditions.

Abstract Phosphoinositide 3‐kinases, delta (PI3Kδ) and gamma (PI3Kγ) are enriched in immune cells and regulate the development and function of innate and adaptive immunity. Dual PI3Kδγ inhibitors are considered high value targets for their potential to treat a variety of immune‐mediated diseases, but their discovery has been challenging. Here we describe the preclinical pharmacology of HM5023507, an orally active dual inhibitor of δγ isoforms in immune signaling. HM5023507 inhibited PI3Kδ and PI3Kγ isoforms with greater than 100‐fold selectivity against PI3Kα and PI3Kβ in recombinant enzymatic assays and in primary human immune cells with an exquisite selectivity against other targets. HM5023507 attenuated the PI3Kδ/γ signaling in human basophils (IC50: 42/340 nmol/L; selectivity ratio ~1:8). HM5023507 attenuated the activation and function of human B and T cells, Th17 differentiation of CD4 T cells in the blood of healthy donors and rheumatoid arthritis patients, and cytokine and IgG production in human T and B cell cocultures, in vitro. Orally dosed HM5023507 attenuated PI3K δ/γ‐mediated immune signaling in the rat in a dose‐related manner. In addition, HM5023507 inhibited semiestablished collagen‐induced arthritic inflammation in the rats (ED50 of 0.25mg/kg, p.o. BID or 0.5 mg/kg, QD, AUC: 1422 ng/mL*h), improved histopathology‐ and micro‐computed tomography (µCT)‐based indices of joint damage, bone destruction, and attenuated the levels of anti‐collagen antibody, with an overall anti‐inflammatory profile matching that of a TNFα neutralizing antibody. The PI3K δγ inhibitory profile of HM5023507 and its selectivity make it a useful tool to further delineate immunobiology of dual PI3K δγ targeting.