Canadian Patient Registries in Motion

July 23, 2024

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Patient registries are coming into their own as vehicles for generating data and insights about rare diseases and treatments.

Complex, laborious, visionary, rich with untapped potential… patient registries are all of these things. Increasingly, stakeholders recognize them as a potent source of real-world data (RWD) that could help support healthcare decision-making and patient access.^12-14 The buzz about registries got even louder in March of 2023, when the federal government announced that Canada’s Drug Agency/ L’agence des medicaments du Canada (CDA-AMC) would receive funding through the National Strategy for Drugs for Rare Diseases to help improve the use of registry data in regulatory and listing decisions for drugs treating rare conditions.¹⁵

With the growing interest in registries, it’s an opportune time to demystify these vital components of the specialty healthcare ecosystem. Some questions we’ll address in this article: How many registries exist in Canada? Who runs them, and how do they do it? What research is CDA-AMC conducting on registries and why? And what opportunities do patient registries in Canada open up, today and tomorrow? 

REGISTRY BASICS

Registries mean different things to different people, and no single definition of “patient registry” serves all purposes in healthcare research.¹ That said, most definitions include the concept of an organized collection of patient data that aims to answer one or more questions about a medical condition or experience and/or treatment outcomes.¹

Researchers at the University of Montreal list at least 3 types of registries – patient registries, disease registries, and product-focused registries.⁶ In addition to registries that look at clinical information like the patient journey or treatment outcomes, registries can also investigate things like diagnostic and prognostic biomarkers, disease-causing gene variants, use of healthcare resources, and clinical trial conduct.^3,5,6,9

The Canadian registry landscape

It’s difficult to pinpoint the exact number of registries in Canada – we know, because we tried! Registries can be as small as a single-clinic patient list or as large as a nationwide database with mandatory reporting, and the total number could reach into the thousands. Unfortunately, no Canadian “registry of registries” exists to capture them all, though some groups have tried to catalogue certain aspects of Canadian registries. For example, CDA-AMC is currently working on a directory of about 130 registries capturing clinical data in rare diseases,¹⁶ and another study has identified over 250 patient support programs (PSPs) – a type of product registry – operating in Canada.¹⁷

Whatever the number, it continues to grow. For example, the National Organization for Rare Diseases (NORD) recently announced the launch of the first public Canadian patient registries for two rare, inherited metabolic disorders: phenylketonuria (PKU) and mucopolysaccharidoses (MPS). These will serve as the first two Canadian registries within NORD’s established IAMRARE® program, a platform that has helped US-based and international registries collect data from more than 18,000 patients in 75 different rare diseases.^18,19

How much does it cost to run a patient registry? By all accounts, a lot – once again, it’s difficult to get down to specific dollars and cents. Funding calls and grant announcements for patient registries indicate that the cost can run into the millions – for example, Brain Canada recently announced a grant of $6 million to establish a new Open Science patient registry at McGill University’s Montreal Neurological Institute-Hospital.²⁰

Responsibility for funding and setting up registries generally falls to either research/academic institutions or to government. In the research model, which has traditionally dominated the registry landscape, institutions or individual researchers define a clinical research question, and then set up a registry using private and/or public funds to collect the relevant data. Many registries for chronic and rare conditions operate in this way, some with funding support from the pharmaceutical industry.¹

Governments may fund registries for certain diseases and conditions, usually with mandatory reporting embedded into the process. The Canadian Cancer Registry (CCR) operates in this way: each province and territory has a legislated responsibility to collect and report standardized information about all cases of cancer (across most tumour types) in their region. Once integrated into the CCR, the data paints a dynamic and comprehensive picture of all Canadian residents, alive or deceased, who have been diagnosed with cancer since 1992.⁴ “The cancer registry is the perfect example of the way that registries should be done,” says Dr. Winson Cheung, a University of Calgary professor and principal director of the Oncology Outcomes (O2) research group. “In all our oncology studies, we have significant confidence that we have an accurate, complete denominator, because cancer is reportable.” That’s the benefit of mandatory reporting: it ensures the data accurately represents the prevalence and incidence of a medical condition in specific populations.²¹

“The cancer registry is the perfect example of the way that registries should be done. In all our oncology studies, we have significant confidence that we have an accurate, complete denominator, because cancer is reportable.

Dr. Winson Cheung, Professor of Medicine, University of Calgary
Principal Director, Oncology Outcomes (O2)

Registry rationale

As a source of data about disease and treatment outcomes, patient registries have several advantages over administrative databases. A disease-based registry often has a well-defined population, with eligibility criteria based on expert consensus. In contrast, administrative databases rely on standardized diagnosis codes, which may not be specific enough to identify a target population, especially when it comes to rare diseases. Registries can also collect various types of data that aren’t always reported in administrative databases, such as functional status, pain levels, and patient-reported outcomes. And while registry data can have multiple sources, most registries follow protocols for standardized data collection. With administrative databases, on the other hand, variations in data collection practices across different healthcare settings makes extrapolation from the data less reliable.⁶

Registries really shine in rare diseases, because they allow researchers and clinicians to look beyond the often-tiny sample sizes in clinical trials and gain a broader, more clinically relevant picture of a rare disease and its treatment landscape.³ By the same token, rare disease registries can help with clinical trial planning and recruitment.²²

Different stakeholder groups have different motivations for their involvement in registries. Clinicians may seek to understand how a disease plays out in the real world to inform their clinical decisions, while physician organizations may look to registry data to assess whether clinicians are managing the disease according to evidence-based guidelines. Patients and advocacy organizations, meanwhile, may use registries as springboards to participate in clinical trials. Health technology assessors and payers can use the wealth of detailed, real-world data to inform cost-effectiveness decisions. Finally, registries can help manufacturers meet their post-marketing surveillance commitments, recruit patients for clinical studies, and identify target markets for new products.³

What can be done with registry data?³

1. Data collection and management. Registries collect a wide variety of data that can cover everything from demographics and medical history to treatment outcomes and patient-reported quality-of-life measures.

2. Epidemiological and natural history studies. Patient registries can provide crucial information for epidemiological studies of disease incidence and prevalence within populations, and for natural history analyses that describe the typical course of a disease and its impact on patients.

3. Clinical research. Registries can improve the reach and relevance of clinical trials. For example, registry data enables clinicals to identify eligible patients who could potentially benefit from a particular trial, initiating discussions with them about their interest in participating.

4. Treatment and outcome assessment. The drug safety and efficacy data collected in registries can inform clinical practice as well as regulatory and listing decisions.

5. Quality improvement. By collecting comprehensive, longitudinal information, registries can help us figure out what’s working well – or not – with a particular disease or treatment, and developing quality improvement initiatives to address any gaps.

REGISTRY CHALLENGES

For all their potential, registries have their fair share of challenges, with workload and data quality topping the list. Some stakeholders have noted that running a registry could result in duplication – not just of data, but also of data management systems and use of healthcare and human resources. It is true that running a registry takes time and effort beyond the workflow of routine clinical care, which can impose an extra burden on healthcare systems already under pressure. Thankfully, some groups have recognized this issue and developed programs to help. In Europe, the European Reference Network (ERN) links registries for selected rare diseases together, enabling centres of expertise and excellence to coordinate their data collection and collaborate on patient care.^6,24

Another well-recognized limitation of patient registries is data quality. For one thing, a rare disease registry may underestimate the prevalence of the condition as its contributions come from a limited number of clinicians.⁶ The observational (rather than interventional) design of most registries may not allow for diligent patient follow-up, which could lead to an underestimation of adverse event rates.²⁵ What’s more, the registry’s design and objectives might not include certain outcomes that turn out to have clinical relevance, such as comorbid conditions, concomitant medications, or hospitalizations.⁶ And in some cases – particularly in rare diseases – the patient numbers are so small that even aggregated data might run the risk of identifying the patients and breaking confidentiality.⁶

Given these challenges and considerations, how can we make registries better? Let’s look at some of the work and thinking going on in Canada today.

REGISTRY INITIATIVES IN CANADA

Improving Canadian registries ranks high on the CDA-AMC’s current priorities. As a starting point, the agency conducted research and found 400 registries covering both rare and common chronic diseases.¹⁶ With a mandate to advance registry data for rare diseases, of which only 10% have an approved therapy for patients,²⁶ the agency narrowed its focus to the 130 registries collecting clinical data on Canadians with rare diseases.

Standards in progress
With that mission accomplished, CDA-AMC is now evaluating the quality and completeness of these registries, collaborating with registry owners to fill in gaps.² Registry standards and guidelines, currently in development by the agency, ensure a high quality of data so that registry data can effectively support regulatory and HTA submissions and life-cycle drug management.

Part of the learning process involves reflecting on past registry experiences and identifying areas that need improvement. In a report called Reflections on the Canadian Bleeding Disorders Registry: Lessons Learned and Future Perspectives, the CDA-AMC identified integration of registry data with electronic medical records (EMR) tools, enhancement of registry reporting modules, regulatory authority requirements, and data-sharing agreements that protect the rights to the data as key challenges to overcome.²⁷

In complement to these activities, a Canadian research network called INFORM RARE, codesigned by healthcare providers, researchers, policymakers, and patients and families, has been working to enhance the development and implementation of Canadian patient registries.²⁸ Along with sustainability, accessibility, and scalability, the group’s “registry values” include using registries for the benefit of affected people and for the public good.

Enrolment required?
Under these admirable ideals lies a burning question: should patients be required to participate in registries? While not a new idea, it deserves a second look. Along with more robust data collection, mandated registry enrolment would enable the capture of more representative populations, thus enhancing the data’s ability to support healthcare decisions.

Consider the Canadian Neuromuscular Disease Registry (CNDR), a voluntary Canada-wide registry of people diagnosed with neuromuscular diseases, including spinal muscular atrophy (SMA). “It would be great to set up the registry so that 100 percent of patients need to participate,” says Susi Vander Wyk, executive director of CURE SMA Canada. “If we explained how mandatory participation improves knowledge of the impact of the disease and the benefits of treatment, it would help generate data that could enable access to those life saving treatments. I believe patients would agree if they understood their information is safe and makes a difference for everyone.” At last formal publication, the newborn screening program for SMA, operating in six provinces and all three territories, yielded an overall screening rate of 72% in Canada.²⁹ With the addition of Quebec to the program in December 2023, the rate has no doubt climbed higher.¹⁶ If the SMA patient registry and newborn screening program could be linked, the registry would become even more representative of the patient population.

“If we explain to patients how mandatory participation in registries would generate data that could help facilitate access to treatment, I think they would agree.”

Susi Vander Wyk
Executive Director, CURE SMA Canada

As a successful model of mandatory enrolment we have the Canadian Fabry Disease Initiative (CDFI), a registry initiated as part of a 10-year real-world clinical study. During the study period, patients seeking enzyme-replacement therapy (ERT) for the disease had to participate in the registry.³⁰ Even when the study achieved its objective – expanded access to ERTs – and enrolment in the registry became voluntary, 77% of patients continued to participate, suggesting overall satisfaction with the process.¹⁴

Combining registries

As the saying goes, there is strength in numbers – no less for registries than for other datasets. When different registries cover similar therapeutic areas, combining them can increase the data’s capacity to support healthcare decision making. Such initiatives call for a collaborative mindset, which is exactly how the Canadian Spondyloarthritis (CanSpA) Research Network came into being. At the time, four independent spondyloarthritis registries were operating in Canada. Acting as a broker of sorts, IQVIA collaborated with each of these registries to put CanSpA on the map.³¹ Developing this “registry of registries” – the first federated rheumatology evidence network in Canada – required coordination of data dictionaries and data transfer among the registries, along with negotiation of fees, contracts, and data-sharing models.

By Canadians, for Canadians

These four Canadian registries are all working toward the same goals: improving treatment access and outcomes through the use of real-world evidence (RWE).

Registry	Architecture	Objectives and outputs
Canadian Neuromuscular Disease Registry (CNDR)	Clinic-based registry of patients with over 10 neuromuscular diseases including amyotrophic lateral sclerosis, spinal muscular atrophy, and Duchenne multiple sclerosis32,33 Established in 2010, with national office at the University of Calgary and 38 affiliated sites16 Capacity to capture all Canadian patients33	Key objectives: increase patient access to research and clinical trials, collect RWE, improve outcomes33 Notable study: first Canadian real-world evidence study of RADICAVA (edaravone), spearheaded by Mitsubishi Tanabe Pharma Canada using data from the CNDR34
Canadian Fabry Disease Initiative (CFDI)	Observational registry of people in Canada living with Fabry disease35 Launched in 2006, jointly funded by government and industry for 10 years and by industry thereafter Owned, designed, and led by clinicians 100% of Canadian Fabry patients captured for first 10 years, with participation now voluntary30,36	Key objectives: provide real-time guidance on indications for publicly funded therapies Notable output: Through the CFDI, Fabry patients received publicly funded access to agalside alpha or beta, Health Canada-approved advanced therapies for Fabry36
Multiple Myeloma Registry (MMR)	Non-profit database of over 8,600 multiple myeloma (MM) patients at 16 Canadian institutions, also storing legacy data dating from 200737 Run by researchers from 16 sites across Canada38 Highly representative of the Canadian MM population	Key objective: track and characterize real-world outcomes of MM patients in Canada Notable output: CMRG data was leveraged to create relevant comparators to clinical trial data for elranatamab, an advanced therapy for MM; the drug subsequently received a “reimburse with conditions” recommendation from CDA-AMC39
Alberta Cancer Registry (ACR)	Population-based registry that collects oncology data of all newly diagnosed cancers and deaths of Alberta40,41 Established in 2002, run by Alberta Health Services and funded by the Government of Canada Captures 100% of cancer patient population in Alberta Information captured: demographic, tumor-related, mortality	Key objective: support cancer prevention, early detection, treatment, research, and improved outcomes Key achievement: only province to achieve gold standard certification from the North American Association of Central Cancer Registries, awarded for the capture of comprehensive, reliable, accurate and timely data

THE FUTURE OF REGISTRIES

One thing we can predict with confidence: technology will play an increasing role in registries of the future. Durhane Wong-Rieger, president of the Canadian Organization for Rare Disorders, sees AI as a “savior that will take registries to the next level.” In her view, “the current construct of patient registries is too rigid.” She envisions technology enabling “more flexible ways of gathering patient data, such as through wearables,” and her wish list includes “the capacity for patients to enter data directly, and platforms that can collect, integrate and use qualitative data.”

“We need more flexible ways of gathering patient data, including the capacity for patients to enter data directly and platforms that can collect, integrate, and use qualitative data. Not everything that counts can be counted.”

Durhane Wong-Rieger
President, Canadian Organization for Rare Disorders

Wong-Rieger’s vision for a brave new registry world is already on the horizon. A new technology platform developed at the University of Toronto allows for clinical-grade data analysis from wearable sensors, such as those found in smartwatches.⁴² Now being deployed at the university’s affiliated hospitals, the technology uses machine learning-based algorithms to extract clinically relevant and reliable data and filter out the rest. A clinician dashboard integrates this information into workflows, adding actionable insights for good measure. 

The Quebec Association for Rare Diseases [Regroupement Québécois des Maladies Orphelines, RQMO] also has digital health on its radar. In collaboration with the University of Sherbrooke, the RQMO is conducting a survey to help the organization understand the value of digital technology to people affected by rare diseases and their caregivers.⁴³ Whether smartphones, smartwatches, glucometers, or connected pillboxes, RQMO wants to know how patients are using these technologies to improve their health.

Looking further into the future, artificial intelligence (AI)-driven advances in record-keeping could drive the current patient registry model to obsolescence. It is no longer fanciful to imagine AI assistants conducting pre-doctor visits, gathering health data, and guiding interviews with patients. As AI evolves, registries will inevitably transition from manual to AI curation. What won’t change: the extraction of meaningful RWE. Tammy Moore, president of ALS [Amyotrophic Lateral Sclerosis] Canada, frames the value of RWE succinctly: “Understanding how innovative treatments perform in a real-world setting can assist stakeholders from across the healthcare system with decision-making and potentially lead to faster access for patients and improved patient outcomes.” ³³

The ultimate value of the data will depend on its rigor, representativeness – and above all, on its relevance to patients. Here’s Wong-Rieger again: “We need to look beyond standard patient-reported outcomes, which can be very constraining to develop, and collect data that is meaningful to the patient.” By the same token, “we need to spend more time educating patients about data ownership and data sharing so they can be registry advocates.”

Not that registries will solve all our data collection problems. “They’re not a panacea, but they can be part of the solution,” says Brad Millson, General Manager, Real World Solutions at IQVIA, adding that “planning for the future is critical. Can you use it to reach out to patients? Can you use it to link datasets within the healthcare system? Can you tie it to outcomes and outcome-based agreements? These are the questions we need to address to future-proof our registries.”

We can be confident that registries will stay with us as the specialized medicine landscape evolves. We have an opportunity to continue raising the quality bar to ensure that registries of the future serve their key purpose — generating evidence to support healthcare decision making and improve patients’ lives.

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