Can we use existing guidance to support the development of robust real-world evidence for health technology assessment/payer decision-making?

Advances in the digitization of health systems and expedited regulatory approvals of innovative treatments have led to increased potential for the use of real-world data (RWD) to generate real-world evidence (RWE) to complement evidence from clinical trials. However, health technology assessment (HTA) bodies and payers have concerns about the ability to generate RWE of sufficient quality to be pivotal evidence of relative treatment effectiveness. Consequently, there is a growing need for HTA bodies and payers to develop guidance for the industry and other stakeholders about the use of RWD/RWE to support access, reimbursement, and pricing. We therefore sought to (i) understand barriers to the use of RWD/RWE by HTA bodies and payers; (ii) review potential solutions in the form of published guidance; and (iii) review findings with selected HTA/payer bodies. Four themes considered key to shaping the generation of robust RWE for HTA bodies and payers were identified as: (i) data (availability, governance, and quality); (ii) methodology (design and analytics); (iii) trust (transparency and reproducibility); and (iv) policy and partnerships. A range of guidance documents were found from trusted sources that could address these themes. These were discussed with HTA experts. This commentary summarizes the potential guidance solutions available to help resolve issues faced by HTA decision-makers in the adoption of RWD/RWE. It shows that there is alignment among stakeholders about the areas that need improvement in the development of RWE and that the key priority to move forward is better collaboration to make data usable for multiple purposes.

Co-construction of health technology assessment recommendations with patients: An example with cardiac defibrillator replacement.

CONTEXT: The National Institute of Excellence in Health and Social Services (INESSS), which functions as the Québec health technology assessment (HTA) agency, tested a new way to engage patients along with health-care professionals in the co-construction of recommendations regarding implantable cardioverter-defibrillator replacement. OBJECTIVE: The objective of this article was to describe the process of co-construction of recommendations and to propose methods of building best practices for patient involvement (PI) in HTA. DESIGN: Throughout the process, documents were collected and participant observations were made. Individual interviews were conducted with patients, health-care professionals and the INESSS scientific team, from January to March 2018. RESULTS: Three committees were established: an expert patient committee to reflect on patient experience literature; an expert health professional committee to reflect on medical literature; and a co-construction committee through which both patients and health-care professionals contributed to develop the recommendations. The expert patients validated and contextualized a literature review produced by the scientific team. This allowed the scientists to consider aspects related to the patient experience and to integrate the feedback from patients into HTA recommendations. The most important factor contributing to a positive PI experience was the structured methodology for selecting patient participants, and a key factor that inhibited the process was a lack of training in PI on the part of the scientific team. CONCLUSIONS: This experience demonstrates that it is possible to co-construct recommendations, even for technically complex HTA subjects, through a more democratic process than usual which led to more patient-focused guidance.

Demonstrating the influence of HTA: INAHTA member stories of HTA impact.

A central function of health technology assessment (HTA) agencies is the production of HTA reports to support evidence-informed policy and decision making. HTA agencies are interested in understanding the mechanisms of HTA impact, which can be understood as the influence or impact of HTA report findings on decision making at various levels of the health system. The members of the International Network of Agencies for HTA (INAHTA) meet at their annual Congress where impact story sharing is one important activity. This paper summarizes four stories of HTA impact that were finalists for the David Hailey Award for Best Impact Story.The methods to measure impact include: document review; claims analysis and review of reimbursement status; citation analysis; qualitative evaluation of stakeholders' views; and review of media response. HTA agency staff also observed changes in government activities and priorities based on the HTA. Impact assessment can provide information to improve the HTA process, for example, the value of patient and clinician engagement in the HTA process to better define the assessment question and literature reviews in a more holistic and balanced way.HTA reports produced by publicly funded HTA agencies are valued by health systems around the globe as they support decision making regarding the appropriate use, pricing, reimbursement, and disinvestment of health technologies. HTAs can also have a positive impact on information sharing between different levels of government and across stakeholder groups. These stories show how HTA can have a significant impact, irrespective of the health system and health technology being assessed.

Factors associated with door-in to door-out delays among ST-segment elevation myocardial infarction (STEMI) patients transferred for primary percutaneous coronary intervention: a population-based cohort study in Ontario, Canada.

BACKGROUND: Compared to ST-segment elevation myocardial infarction (STEMI) patients who present at centres with catheterization facilities, those transferred for primary percutaneous coronary intervention (PCI) have substantially longer door-in to door-out (DIDO) times, where DIDO is defined as the time interval from arrival at a non-PCI hospital, to transfer to a PCI hospital. We aimed to identify potentially modifiable factors to improve DIDO times in Ontario, Canada and to assess the impact of DIDO times on 30-day mortality. METHODS: A population-based, retrospective cohort study of 966 STEMI patients transferred for primary PCI in Ontario in 2012 was conducted. Baseline factors were examined across timely DIDO status. Multivariate logistic regression was used to examine independent predictors of timely DIDO as well as the association between DIDO times and 30-day mortality. RESULTS: The median DIDO time was 55 min, with 20.1% of patients achieving the recommended DIDO benchmark of ≤30 min. Age (OR> 75 vs 18-55 0.30, 95% CI: 0.16-0.56), symptom-to-first medical contact (FMC) time (OR61-120mins vs < 60mins 0.60, 95% CI: 0.39-0.90; OR>120mins vs < 60mins 0.53, 95% CI:0.35-0.81) and emergency medical services transport with a pre-hospital electrocardiogram (ECG) (OREMS transport + ECG vs self-transport 2.63, 95% CI:1.59-4.35) were the strongest predictors of timely DIDO. Patients with timely ECG were more likely to have recommended DIDO times (33.0% vs 12.3%; P < 0.001). A significantly higher proportion of those who met the DIDO benchmark had timely FMC-to-balloon times (78.7% vs 27.4%; P < 0.001). Compared to patients with DIDO time ≤ 30 min, those with DIDO times > 90 min had significantly higher adjusted 30-day mortality rates (OR 2.82, 95% CI:1.10-7.19). CONCLUSIONS: While benchmark DIDO times were still rarely achieved in the province, we identified several potentially modifiable factors in the STEMI system that might be targeted to improve DIDO times. Our findings that patients who received a pre-hospital ECG were still being transferred to non-PCI capable centres suggest strategies addressing this gap may improve patient outcomes.

Transfer of patients with ST-elevation myocardial infarction for primary percutaneous coronary intervention: a province-wide evaluation of "door-in to door-out" delays at the first hospital.

BACKGROUND: Interhospital transfer of patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PPCI) is associated with longer delays to reperfusion, related in part to turnaround ("door in" to "door out," or DIDO) time at the initial hospital. As part of a systematic, province-wide evaluation of STEMI care, we examined DIDO times and associations with patient, hospital, and process-of-care factors. METHODS AND RESULTS: We performed medical chart review for STEMI patients transferred for PPCI during a 6-month period (October 1, 2008, through March 31, 2009) and linked these data to ambulance service databases. Two core laboratory cardiologists reviewed presenting ECGs to identify left bundle-branch block and, in the absence of left bundle-branch block, definite STEMI (according to both cardiologists) or an ambiguous reading. Median DIDO time was 51 minutes (25th to 75th percentile: 35-82 minutes); 14.1% of the 988 patients had a timely DIDO interval (≤30 minutes as recommended by guidelines). The data-to-decision delay was the major contributor to DIDO time. Female sex, more comorbidities, longer symptom duration, arrival by means other than ambulance, arrival at a hospital not exclusively transferring for PPCI, arrival at a center with a low STEMI volume, and an ambiguous ECG were independently associated with longer DIDO time. When turnaround was timely, 70% of patients received timely PPCI (door-to-device time ≤90 minutes) versus 14% if turnaround was not timely (P<0.0001). CONCLUSIONS: Benchmark DIDO times for STEMI patients transferred for PPCI were rarely achieved. Interventions aimed at facilitating the transfer decision, particularly in cases of ECGs that are difficult to interpret, are likely to have the best impact on reducing delay to reperfusion.

A new metric for centralization of ruptured abdominal aortic aneurysm repair in large territories.

OBJECTIVE: This study proposes the DEDE (Door-from-Emergency to Door-to-EVAR [endovascular aneurysm repair]) time as a new metric for ruptured abdominal aortic aneurysm (RAAA) delay time to surgery, permitting coherent centralization in large territories. It demonstrates how the DEDE time can be applied, using data from the province of Quebec, and looks at its potential effect on 30-day mortality. METHODS: We used the Quebec Integrated Chronic Disease Surveillance System (QICDSS), the linkage of five health administrative databases, to build a retrospective cohort of RAAA patients repaired operatively between April 1, 2006, and March 31, 2013. A validated algorithm was used to identify open surgical repair (OSR) and EVAR patients. Hospitals performing these operations were further characterized according to their location, volume of RAAA, types of surgeries (OSR vs EVAR), and surgeon's volume. Logistic and log-binomial regression analyses identified the risk of 30-day mortality with age, sex, hospital volume, and surgical groups as variables. Using the DEDE 90 metric and the attributable fraction, we projected how centralization and increasing the number of EVAR would affect the 30-day mortality. RESULTS: Among patients aged ≥65 years, 895 RAAAs were identified. OSR was performed in 839 patients (93.7%) and EVAR in 56 (6.3%). The overall 30-day mortality was 34.4%, and more specifically, was 35.5% for OSR compared with 17.9% for EVAR (P = .0046). RAAAs were treated in 39 hospitals, including 16 centers averaging less than one RAAA repair per year. Low-volume (39.4%) vs high-volume centers (32.5%) had similar 30-day mortality (P = .2198). In the multivariate analysis, the relative risk for OSR was 1.95 (P = .0211) and was not significant for hospital volume. Applying the DEDE 90 metric and increasing access to EVAR to 50% of patients, the overall 30-day mortality would be 26.8%. CONCLUSIONS: DEDE 90 is a new metric for a coherent centralization model, particularly in large territories, where transport time is crucial. Increasing access to EVAR performed in high-volume centers, with consideration to transport time, could improve the 30-day mortality after a RAAA repair.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Framework for Multistakeholder Patient Registries in the Field of Rare Diseases: Focus on Neurogenetic Diseases.

Progress in genetic diagnosis and orphan drug legislation has opened doors to new therapies in rare neurogenetic diseases (RNDs). Innovative therapies such as gene therapy can improve patients' quality of life but come with academic, regulatory, and financial challenges. Registries can play a pivotal role in generating evidence to tackle these, but their development requires multidisciplinary knowledge and expertise. This study aims to develop a practical framework for creating and implementing patient registries addressing common challenges and maximizing their impact on care, research, drug development, and regulatory decision making with a focus on RNDs. A comprehensive 3-step literature and qualitative research approach was used to develop the framework. A qualitative systematic literature review was conducted, extracting guidance and practices leading to the draft framework. Subsequently, we interviewed representatives of 5 established international RND registries to add learnings from hands-on experiences to the framework. Expert input on the draft framework was sought in digital multistakeholder focus groups to refine the framework. The literature search; interviews with 5 registries; and focus groups with patient representatives (n = 4), clinicians (n = 6), regulators, health technology assessment (HTA) bodies and payers (n = 7), industry representatives (n = 7), and data/information technology (IT) specialists (n = 5) informed development of the framework. It covers the interests of different stakeholders, purposes for data utilization, data aspects, IT infrastructure, governance, and financing of rare disease registries. Key principles include that data should be rapidly accessible, independent, and trustworthy. Governance should involve multiple stakeholders. In addition, data should be highly descriptive, machine-readable, and accessible through a shared infrastructure and not spread over multiple isolated repositories. Sustainable and independent financing of registries is deemed important but remains challenging because of a lack of widely supported funding models. The proposed framework will guide stakeholders in establishing or improving rare disease registries that fulfill requirements of academics and patients as well as regulators, HTA bodies, and commercial parties. There is a need for more clarity regarding quality requirements for registries in regulatory and HTA context. In addition, independent financing models for registries should be developed, as well as well-defined policies on technical uniformity in health data.

The State of Heart Failure Care in Canada: Minimal Improvement in Readmissions Over Time Despite an Increased Number of Evidence-Based Therapies.

Background: An unanswered question is whether the combination of advances in medical and device therapy over the past decade has translated into improved outcomes for patients with heart failure (HF) in Canada. Methods: The Canadian Institute for Health Information (CIHI) Hospital Morbidity Database was used to identify hospitalizations for HF among patients aged 18 years and older in Canadian hospitals during fiscal years 2009/2010 and 2018/2019. We assessed interprovincial differences in age, sex, length of stay (LOS), discharge disposition, type of admitting hospital, and most responsible service, for all HF admissions. National and provincial rates of HF admissions and all-cause 30-day readmissions were calculated. Results: After adjusting for age, the rate of HF admissions in Canada was 216 per 100,000 population in 2009/2010 and 2018/2019. The majority of patients with HF were admitted to general internal medicine and community hospitals in both 2009/2010 and 2018/2019. The national, crude, all-cause 30-day readmission rate stayed constant at 20.6%, and the majority of patients were readmitted with the diagnosis of HF in both 2009/2010 (62.5%) and 2018/2019 (59.0%). Median and interquartile range of HF LOS also remained unchanged at 7 days (3-14). Conclusions: The national rate of HF admissions, 30-day readmissions, and HF LOS have remained unchanged from 2009/2010 to 2018/2019, despite advances in medical and device therapy during this timeframe.

Introduction: La question demeure de savoir si, au cours de la dernière décennie au Canada, la combinaison des avancées dans les traitements médicaux et à l'aide d'un dispositif s'est traduite par de meilleurs résultats cliniques chez les patients atteints d'insuffisance cardiaque (IC). Méthodes: Nous avons utilisé la base de données sur la morbidité hospitalière de l'Institut canadien d'information sur la santé (ICIS) pour recenser les hospitalisations de patients atteints d'IC âgés de 18 ans et plus dans les hôpitaux du Canada au cours des années financières 2009/2010 et 2018/2019. Nous avons évalué les différences interprovinciales selon l'âge, le sexe, la durée du séjour (DDS), l'état à la sortie, le type d'hôpital à l'admission et le service le plus tenu à la prise en charge du patient, de toutes les admissions liées à l'IC. Nous avons calculé les taux provinciaux et national des admissions liées à l'IC et les réadmissions toutes causes confondues dans les 30 jours. Résultats: Après ajustement en fonction de l'âge, le taux d'admissions liées à l'IC au Canada était de 216 pour 100 000 habitants en 2009/2010 et en 2018/2019. La majorité des patients atteints d'IC avaient été admis en médecine interne générale et dans les hôpitaux communautaires en 2009/2010 et en 2018/2019. Le taux national, brut, toutes causes confondues de réadmissions dans les 30 jours était resté constant à 20,6 %, et la majorité des patients avaient eu des réadmissions liées au diagnostic d'IC en 2009/2010 (62,5 %) et en 2018/2019 (59,0 %). L'écart interquartile et la médiane de la DDS liée à l'IC étaient aussi demeurés inchangés après 7 jours (3-14). Conclusions: Le taux national des admissions liées à l'IC, les réadmissions dans les 30 jours et la DDS liée à l'IC étaient demeurés inchangés de 2009/2010 à 2018/2019, malgré les avancées des traitements médicaux et à l'aide d'un dispositif durant cette période de temps.

Surveillance for Outcomes Selected as Atrial Fibrillation Quality Indicators in Canada: 10-Year Trends in Stroke, Major Bleeding, and Heart Failure.

BACKGROUND: Whether advances in identification and management of atrial fibrillation and atrial flutter (collectively, AF) have led to improved outcomes is unclear. We sought to study trends in clinical outcomes selected as quality indicators for nonvalvular AF in Canada. METHODS: We identified hospitalized patients with a first diagnosis of nonvalvular AF between April 2006 and March 2015, in all of Canada except Quebec. We assessed trends in 1-year incidence of stroke/systemic embolism (SSE), major bleeding, and initial heart failure (HF) hospitalization. RESULTS: The cohort included 466,476 patients. The median age was 77 years (interquartile range, 68-84 years), 46% were female, and 68% had a Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score > 3. Within 1 year of discharge, 3.5% were hospitalized for stroke or SSE, 1.6% for major bleeding, and 8.6% for new HF. Over the study period, the crude rate of SSE declined from 3.6% to 3.3% (P = 0.002), whereas the rates of hospitalization for new HF and for major bleeding did not significantly change. After adjustment for CHA2DS2-VASc score, the yearly rates of incident SSE (risk ratio, 0.99; 95% confidence interval [CI], 0.98-0.99; P = 0.002) and HF (risk ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) declined ≤ 1% absolute, whereas major bleeding remained unchanged (risk ratio, 1.00; 95% CI, 0.99-1.00; P = 0.28). CONCLUSIONS: Among hospitalized patients with nonvalvular AF in Canada, the rate of SSE and new HF decreased modestly over a 10-year period, with no significant change in major bleeding. Efforts to study process-based quality indicators, with increased focus on HF prevention, are needed.

CONTEXTE: On ne sait pas si les avancées en matière de détection et de prise en charge de la fibrillation auriculaire et du flutter auriculaire (collectivement appelés « FA ¼ ci-après) ont permis d'améliorer les résultats pour les patients. Nous avons donc étudié les tendances à l'égard de résultats cliniques particuliers pris comme indicateurs de qualité relatifs à la FA non valvulaire au Canada. MÉTHODOLOGIE: Nous avons recensé les patients hospitalisés au Canada (sauf au Québec) entre avril 2006 et mars 2015 en raison d'une FA non valvulaire nouvellement diagnostiquée. Nous avons évalué les tendances quant à la survenue d'un accident vasculaire cérébral ou d'une embolie systémique (AVC/ES), d'une hémorragie majeure et d'une première hospitalisation pour insuffisance cardiaque. RÉSULTATS: La cohorte comprenait 466 476 patients, dont l'âge médian était de 77 ans (intervalle interquartile : 68 à 84 ans); 46 % des patients étaient des femmes, et 68 % avaient un score CHA2DS2-VASc ( C ongestive Heart Failure [insuffisance cardiaque congestive], hypertension, âge [≥ 75 ans], diabète, S troke/Transient Ischemic Attack [AVC/accident ischémique transitoire] ­ maladie vasculaire, âge [65-74 ans], sexe [femmes]) supérieur à 3. Dans l'année suivant la sortie de l'hôpital, 3,5 % des patients ont été hospitalisés en raison d'un AVC ou d'un AVC/ES, 1,6 %, en raison d'une hémorragie majeure et 8,6 %, en raison d'une nouvelle insuffisance cardiaque. Au cours de la période étudiée, le taux brut d'AVC/ES est passé de 3,6 % à 3,3 % (p = 0,002), tandis que les taux d'hospitalisation en raison d'une nouvelle insuffisance cardiaque ou d'une hémorragie majeure n'ont pas changé de manière significative. Après correction pour tenir compte du score CHA2DS2-VASc, les taux annuels de survenue d'un AVC/ES (rapport des risques de 0,99; intervalle de confiance [IC] à 95 % : de 0,98 à 0,99; p = 0,002) et d'une insuffisance cardiaque (rapport des risques de 0,99; IC à 95 % : de 0,99 à 1,00; p = 0,001) ont diminué de ≤ 1 % en valeur absolue, tandis que le taux de survenue d'une hémorragie majeure n'a pas changé (rapport des risques : 1,00; IC à 95 % : de 0,99 à 1,00; p = 0,28). CONCLUSIONS: Parmi les patients hospitalisés au Canada en raison d'une FA non valvulaire, les taux d'AVC/ES et de nouvelle insuffisance cardiaque ont affiché une réduction modeste sur une période de 10 ans, tandis que le taux d'hémorragie majeure n'a pas changé de manière significative. D'autres études évaluant les indicateurs de qualité fondés sur les procédés, notamment en matière de prévention de l'insuffisance cardiaque, s'imposent.

Development of Acute Myocardial Infarction Mortality and Readmission Models for Public Reporting on Hospital Performance in Canada.

BACKGROUND: Given changes in the care and outcomes of acute myocardial infarction (AMI) patients over the past several decades, we sought to develop prediction models that could be used to generate accurate risk-adjusted mortality and readmission outcomes for hospitals in current practice across Canada. METHODS: A Canadian national expert panel was convened to define appropriate AMI patients for reporting and develop prediction models. Preliminary candidate variable evaluation was conducted using Ontario patients hospitalized with a most responsible diagnosis of AMI from April 1, 2015 to March 31, 2018. National data from the Canadian Institute for Health Information was used to develop AMI prediction models. The main outcomes were 30-day all-cause in-hospital mortality and 30-day urgent all-cause readmission. Discrimination of these models (measured by c-statistics) was compared with that of existing Canadian Institute for Health Information models in the same study cohort. RESULTS: The AMI mortality model was assessed in 54,240 Ontario AMI patients and 153,523 AMI patients across Canada. We observed a 30-day in-hospital mortality rate of 6.3%, and a 30-day all-cause urgent readmission rate of 10.7% in Canada. The final Canadian AMI mortality model included 12 variables and had a c-statistic of 0.834. For readmission, the model had 13 variables and a c-statistic of 0.679. Discrimination of the new AMI models had higher c-statistics compared with existing models (c-statistic 0.814 for mortality; 0.673 for readmission). CONCLUSIONS: In this national collaboration, we developed mortality and readmission models that are suitable for profiling performance of hospitals treating AMI patients in Canada.

CONTEXTE: Compte tenu des changements apportés au cours des dernières décennies aux soins des patients ayant subi un infarctus aigu du myocarde (IAM) et aux issues d'un tel événement, nous avons voulu élaborer des modèles prédictifs pouvant servir à calculer de façon précise les résultats relatifs à la mortalité et aux réadmissions, ajustés selon les risques, pour les hôpitaux dans la pratique actuelle au Canada. MÉTHODOLOGIE: Un groupe national d'experts canadiens a été mis sur pied et a reçu le mandat de définir les critères appropriés applicables aux patients ayant subi un IAM aux fins de déclaration des cas et d'élaborer des modèles prédictifs. L'évaluation préliminaire des variables proposées a été effectuée à partir de patients hospitalisés en Ontario entre le 1er avril 2015 et le 31 mars 2018 chez lesquels l'IAM était le diagnostic principal à l'origine de l'hospitalisation. Les données à l'échelle nationale de l'Institut canadien d'information sur la santé (ICIS) ont été utilisées pour élaborer des modèles prédictifs d'IAM. Les deux principales issues évaluées étaient la mortalité hospitalière toutes causes confondues à 30 jours et la réadmission urgente toutes causes confondues à 30 jours. Le pouvoir discriminant de ces modèles (mesuré par la statistique C) a été comparé à celui des modèles existants de l'ICIS dans la même cohorte de l'étude. RÉSULTATS: Le modèle de mortalité par IAM a été évalué auprès de patients ayant subi un IAM, dont 54 240 en Ontario et 153 523 dans l'ensemble du Canada. Nous avons observé un taux de mortalité hospitalière à 30 jours de 6,3 % et un taux de réadmission urgente à 30 jours toutes causes confondues de 10,7 % au Canada. Le modèle canadien final de prédiction de la mortalité par IAM était constitué de 12 variables et avait une statistique C de 0,834. Pour la réadmission, le modèle comportait 13 variables et présentait une statistique C de 0,679. Le pouvoir discriminant des nouveaux modèles d'IAM présentait une statistique C supérieure à celle des modèles existants (statistique C de 0,814 pour la mortalité et de 0,673 pour la réadmission). CONCLUSIONS: Dans le cadre de cette collaboration nationale, nous avons élaboré des modèles prédictifs de la mortalité et de la réadmission hospitalière qui permettent d'établir un profil des résultats obtenus par les hôpitaux traitant des patients ayant subi un IAM au Canada.

Association between timeliness of reperfusion therapy and clinical outcomes in ST-elevation myocardial infarction.

CONTEXT: Guidelines emphasize the importance of rapid reperfusion of patients with ST-elevation myocardial infarction (STEMI) and specify a maximum delay of 30 minutes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI). However, randomized trials and selective registries are limited in their ability to assess the effect of timeliness of reperfusion on outcomes in real-world STEMI patients. OBJECTIVES: To obtain a complete interregional portrait of contemporary STEMI care and to investigate timeliness of reperfusion and outcomes. DESIGN, SETTING, AND PATIENTS: Systematic evaluation of STEMI care for 6 months during 2006-2007 in 80 hospitals that treated more than 95% of patients with acute myocardial infarction in the province of Quebec, Canada (population, 7.8 million). MAIN OUTCOME MEASURES: Death at 30 days and at 1 year and the combined end point of death or hospital readmission for acute myocardial infarction or congestive heart failure at 1 year by linkage to Quebec's medicoadministrative databases. RESULTS: Of 1832 patients treated with reperfusion, 392 (21.4%) received fibrinolysis and 1440 (78.6%) received PPCI. Fibrinolysis was untimely (>30 minutes) in 54% and PPCI was untimely (>90 minutes) in 68%. Death or readmission for acute myocardial infarction or heart failure at 1 year occurred in 13.5% of fibrinolysis patients and 13.6% of PPCI patients. When the 2 treatment groups were combined, patients treated outside of recommended delays had an adjusted higher risk of death at 30 days (6.6% vs 3.3%; odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21-3.93) and a statistically nonsignificant increase in risk of death at 1 year (9.3% vs 5.2%; OR, 1.61; 95% CI, 1.00-2.66) compared with patients who received timely treatment. Patients treated outside of recommended delays also had an adjusted higher risk for the combined outcome of death or hospital readmission for congestive heart failure or acute myocardial infarction at 1 year (15.0% vs 9.2%; OR, 1.57; 95% CI, 1.08-2.30). At the regional level, after adjustment, each 10% increase in patients treated within the recommended time was associated with a decrease in the region-level odds of overall 30-day mortality (OR, 0.80; 95% CI, 0.65-0.98). CONCLUSION: Among patients in Quebec with STEMI, reperfusion delivered outside guideline-recommend delays was associated with significantly increased 30-day mortality, a statistically nonsignificant increase in 1-year mortality, and significantly increased risk of the composite of mortality or readmission for acute myocardial infarction or heart failure at 1 year.

Inequity in Access to Transcatheter Aortic Valve Replacement: A Pan-Canadian Evaluation of Wait-Times.

BACKGROUND: There has been an exponential increase in the demand for transcatheter aortic valve replacement (TAVR). Our goal was to examine trends in TAVR capacity and wait-times across Canada. METHODS: All TAVR cases were identified from April 1, 2014, to March 31, 2017. Wait-time was defined as the duration in days from the initial referral to the TAVR procedure. TAVR capacity was defined as the number of TAVR procedures per million population/province/fiscal year. We performed multivariable multilevel Cox proportional hazards modelling of the time to TAVR as the dependant variable and the effect of provinces as random effects. We quantified the variation in wait-times among provinces using the median hazard ratio. RESULTS: We identified a total of 4906 TAVR procedures across 9 provinces. Despite a year over year increase in overall capacity, there was a greater than 3-fold difference in capacity between provinces. Crude median wait-times increased over time in all provinces, with marked variation from 71.5 days in Newfoundland to 190.5 and 203 days in Manitoba and Alberta, respectively. This suggests increasing demand outpaced the growth in capacity. We found a median hazard ratio of 1.62, indicating that in half of the possible pairwise comparisons, the time to TAVR for identical patients was at least 62% longer between different provinces. CONCLUSION: We found substantial geographic inequity in TAVR access. This calls for policy makers, clinicians, and administrators across Canada to address this inequity through revaluation of provincial funding mechanisms, as well as implementation of efficient care pathways.

An Update on the Development and Feasibility Assessment of Canadian Quality Indicators for Atrial Fibrillation and Atrial Flutter.

BACKGROUND: In 2010, the Canadian Cardiovascular Society Atrial Fibrillation/Atrial Flutter (AF/AFL) quality indicator (QI) working group was established to develop QIs and assess feasibility of measurement. After extensive review, 3 priority QIs were selected. However, none were measurable at a national level. METHODS: The working group reconvened in 2017 to review the relevance of previously proposed QIs, identify opportunities to develop new QIs, and propose an initial strategy for measuring and reporting. RESULTS: Two additional priority QIs were added to the previous 3: proportion of patients with nonvalvular (NV) AF/AFL sorted by stroke risk stratum and annual rate of hospitalization for a new heart failure diagnosis. An environmental scan was undertaken to determine the potential of existing databases to provide national and provincial estimates. On the basis of validated administrative codes, the Canadian Institute for Health Information discharge abstract database can be used for inpatients. In collaboration with the Canadian Primary Care Sentinel Surveillance Network, 2 of the 5 QIs can be assessed in outpatients (patients with NVAF/AFL sorted by stroke risk stratum and high risk for stroke NVAF/AFL receiving oral anticoagulation). Stroke prevention therapy can be further measured in selected provinces with linked databases including prescriptions. CONCLUSIONS: This first step could provide a better initial understanding of the quality of AF/AFL care in Canada, but important gaps in the meaningful measurement of QIs remain. The AF/AFL QI working group has limited capacity to make progress without national level leadership and the resources to support data aggregation, data analysis, and pan-Canadian reporting.

CONTEXTE: En 2010, le groupe de travail des indicateurs de qualité (IQ) de la Société canadienne de cardiologie sur la fibrillation auriculaire (FA) et le flutter auriculaire (FLA) a été mis sur pied pour élaborer des IQ et évaluer la faisabilité d'utiliser ces IQ comme outils de mesure. Après un examen approfondi, trois IQ prioritaires ont été sélectionnés, mais aucun n'a pu être mesuré à l'échelle nationale. MÉTHODOLOGIE: Le groupe de travail s'est réuni à nouveau en 2017 afin d'examiner la pertinence des IQ proposés au départ, de recenser des occasions d'élaborer de nouveau IQ et de proposer une stratégie initiale de mesure et de production de rapports à cet égard. RÉSULTATS: Deux IQ prioritaires supplémentaires ont été ajoutés aux trois premiers : la proportion de patients atteints de FA non valvulaire (FANV) ou de FLA ayant fait l'objet d'un tri selon la strate de risque d'AVC et le taux annuel d'hospitalisations attribuables à un nouveau diagnostic d'insuffisance cardiaque. Une analyse de l'environnement a été réalisée afin de déterminer si les bases de données existantes pouvaient fournir des estimations nationales et provinciales. Dans le cas de patients hospitalisés, on peut utiliser la Base de données sur les congés des patients de l'Institut canadien d'information sur la santé en se servant de codes administratifs validés. Dans le cas de patients non hospitalisés (patients atteints de FANV/FLA, triés par strate de risque, exposés à un risque élevé d'AVC en raison d'une FANV ou d'un FLA et recevant une anticoagulation orale), on peut mesurer deux des cinq IQ, en collaboration avec le Réseau canadien de surveillance sentinelle en soins primaires. Le traitement préventif de l'AVC peut continuer à faire l'objet de mesures dans certaines provinces grâce aux bases de données interreliées, comme les bases de données sur les ordonnances. CONCLUSIONS: Cette première étape a permis d'obtenir une meilleure compréhension initiale de la qualité de la prise en charge de la FA et du FLA au Canada, mais d'importantes lacunes restent à combler pour rendre pertinente la mesure des IQ. Le groupe de travail des IQ sur de la FA et le FLA n'a pas toutes les capacités requises pour réaliser des progrès en l'absence de leadership national et de ressources permettant de soutenir le regroupement et l'analyse des données, ainsi que la production de rapports à l'échelle pancanadienne.

2019 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Guidelines on the Acute Management of ST-Elevation Myocardial Infarction: Focused Update on Regionalization and Reperfusion.

Rapid reperfusion of the infarct-related artery is the cornerstone of therapy for the management of acute ST-elevation myocardial infarction (STEMI). Canada's geography presents unique challenges for timely delivery of reperfusion therapy for STEMI patients. The Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology STEMI guideline was developed to provide advice regarding the optimal acute management of STEMI patients irrespective of where they are initially identified: in the field, at a non-percutaneous coronary intervention-capable centre or at a percutaneous coronary intervention-capable centre. We had also planned to evaluate and incorporate sex and gender considerations in the development of our recommendations. Unfortunately, inadequate enrollment of women in randomized trials, lack of publication of main outcomes stratified according to sex, and lack of inclusion of gender as a study variable in the available literature limited the feasibility of such an approach. The Grading Recommendations, Assessment, Development, and Evaluation system was used to develop specific evidence-based recommendations for the early identification of STEMI patients, practical aspects of patient transport, regional reperfusion decision-making, adjunctive prehospital interventions (oxygen, opioids, antiplatelet therapy), and procedural aspects of mechanical reperfusion (access site, thrombectomy, antithrombotic therapy, extent of revascularization). Emphasis is placed on integrating these recommendations as part of an organized regional network of STEMI care and the development of appropriate reperfusion and transportation pathways for any given region. It is anticipated that these guidelines will serve as a practical template to develop systems of care capable of providing optimal treatment for a wide range of STEMI patients.

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients.

HIV infection leads to decreases in the number of CD4 T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO-) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.

Quality of Cardiac Care in Canada: Recommendations for Building a Sustainable Future.

Cardiovascular (CV) disease continues to present a significant disease and economic burden in Canada. To improve the quality of care and ensure sustainability of services, a national quality improvement initiative is required. The purpose of this analysis was to review the evidence for public reporting (PR) and external benchmarking (EB) to improve patient outcomes, and to recommend a strategy to improve CV care in Canada. To incorporate recent literature, the Canadian Cardiovascular Society (CCS) commissioned the Institute of Health Economics to provide a rapid update on the literature of PR and EB. The review showed that EB is more likely to promote positive effects, such as improved mortality, morbidity, and evidence-based clinical practice, and to limit negative effects, such as access restrictions or unintended provider behaviour associated with some forms of "top-down" PR. On the basis of these findings, this we recommend the following: (1) secure funding for the provincial collection of CV quality indicators and the creation of annual National CV Quality Reports; (2) enhance the culture of using CV quality indicator data for continuous quality improvement and opportunities for national or regional EB and sharing best practices; and (3) implement ongoing evaluation and revision of CCS clinical practice guidelines incorporating key quality indicators. This is already under way to a limited extent by the CCS with its Quality Project, but intentional, sustained support needs to be secured to enhance this ongoing effort and improve the quality of CV care for all Canadians.

The Transcatheter Aortic Valve Implantation (TAVI) Quality Report: A Call to Arms for Improving Quality in Canada.

Transcatheter aortic valve implantation (TAVI) is a disruptive technology that has dramatically changed the way clinicians care for patients with aortic stenosis. In 15 short years, this technology has progressed from first-in-human to the standard of care for high-risk and inoperable patients with aortic stenosis. In 2016 the Canadian Cardiovascular Society published the first ever report of quality of care for TAVI in Canada. This report provided multiple insights into evaluating such care delivered to Canadians and the challenges that lie ahead. In this article, we summarize these challenges and encourage cardiologists to join the call to arms for improving quality of TAVI care in Canada.