Response to: Consultation: Health Canada’s Clinical Trials Regulatory Modernization Initiative
Submitted by: Canadian Organization for Rare Disorders
The Canadian Organization for Rare Disorders (CORD) has prepared this document as a supplement to our submission to Health Canada’s Clinical Trials Regulatory Modernization Initiative through the online portal to share our response with our community.
The Canadian Organization for Rare Disorders is an umbrella organization with a core membership of approximately 100 rare disease patient organizations but also a diversified cohort of organization and individual participants that includes patient organizations representing both common and rare conditions, research initiatives, clinical networks, and industry. CORD’s response represents our perspectives on behalf of the Canadian rare disease patient community but has not been circulated for endorsement by members.
2. What describes your clinical trial activity (select all that apply):
CORD engages in clinical trial activity in several ways.
CORD is interested in and engaged in various ways with clinical trials related to drugs, medical devices, and natural health products as well as nutritional supplements, diagnostic tests, digital health technologies (apps, electronic health and medical records, and wearable devices), and interventions for mental health and supportive care.
4. Do you anticipate any benefits or impacts of the following proposals for your organization?
The agile life-cycle approach
The single authorization for multiple products
The risk-based approach
The use of terms and conditions on a clinical trial authorization
Decentralized trials
a. The agile life-cycle approach is fundamental to almost all technologies for rare diseases, not just breakthrough, complex, or highly innovative products but also expanded indications for older or already approved products, repurposed drugs, combination and sequential use of therapies, targeted therapies, single-patient designer therapies, and “in-research-only” access programmes.
We strongly endorse HC’s proposed agile life-cycle approach to CT authorization, including innovative trial designs, such as basket trials, umbrella trials and platform trials. We also point to the “complex innovative trial design” approach by the US Food and Drug Administration which includes (learning) pilot projects and highly flexible trial designs based on the exigencies of the situation. We are also very supportive of Health Canada’s alignment with other international regulatory agencies, in particular, the OECD countries and urge consensus on terminology, definitions, and perhaps a taxonomy of trial designs that include “agile life-cycle” approach, flexible designs, adaptive designs and specific innovative trial designs.
A major concern that not only compromises the use of “novel” trial designs but actually negates their desired impact of providing more timely and appropriate access to innovative therapies is acceptance by the health technology assessors and reimbursors. We already experience over and over the discounting and outright rejection of therapies that are approved with short, Phase 2 CTs, small number of trial participants, single-arm, biomarker outcomes, etc., etc. It is imperative that Health Canada work directly with the HTA agencies and the payers to assure agreement with the trial design and acceptance of the outcome with compatible life-cycle access programmes, namely, performance-based access, “coverage with evidence developing”, or “pay for performance” schemes.
CORD is also very interested in agile approaches that appropriately encourage “single-patient” clinical trials that can also be applied very rapidly in life-threatening, urgent, or time-sensitive cases.
Finally, in all of these approaches, we call upon Health Canada to directly engage the relevant patient and clinical community, regardless of the entity that is sponsoring the clinical trial, to ensure the needs and preferences of patients are at the centre of all activities.
b. For rare diseases where the patient populations can be quite small and the number of eligible participants even more limited, a single authorization for multiple product types, including drugs, natural health products and medical devices, may not only be more efficient but may actually be the only way to conduct testing, especially when products are complementary in modes of action or effect.
c. CORD recognizes the risk-based approach as potentially valuable to reducing time and burden of bringing products to patients and is supportive of the approach. However, we have a number of very important caveats or conditions that need to be addressed to assure that this approach does lead to timely, appropriate access for patients in the real world. First, there must be as much clarity and transparency as possible in the designation of risk category. Obviously, technologies will not fit neatly and the process and rational for assignation must be include consultation with all relevant stakeholders, including the patients and clinicians. Moreover, there must be opportunity not only to provide input but also to appeal and to recategorize based specific criteria or emergence of new data.
Second, while it is desirable that the articulation of the risk approach is compatible with those of other countries, the timing of the application and the adjudication may not be consistent across jurisdictions, which raises the question, “now what?” We cannot avoid the possibility that applicants will proceed selectively in those countries with the lowest barriers, so It is important to anticipate these situations and to put contingencies in place.
Third, it is imperative that a risk-based approach does not create a barrier to access in the real world. As discussed in point (a), we have ample experience here in Canada where the health technology assessment agencies have discounted the value of data from CTs other than full robust RCTs that “achieve” traditional significance levels.
d. The “use of terms and conditions on a clinical trial authorization before or during the clinical trial in a predictable and agile manner that is consistent across product lines” sounds highly desirable. We urge Health Canada to provide specifications on the process, examples of how this would be applied, and how “predictability” and “agility” will be simultaneously addressed without being reductive. As importantly, we urge that the process in definition and application includes consultation with patients and clinicians in as transparent a way as possible to avoid any “unintended” consequences, especially those that would have potentially detrimental impact on patient.
e. Decentralized trials have been in widespread use for rare disease therapies for a long time, mainly out of necessity, given the broad geographic dispersion of very small patient populations. We have seen a proliferation as a result of the pandemic and especially with introduction of digital tools, remote management and “direct-to-patient” products and services. We urge Health Canada, in collaboration with other regulators, to standardize and validate digital tools, remote management, and data collection, analysis and use.
Obvious beneficiaries of decentralized trials are patients and clinicians, improving equity of opportunity for patients and clinicians who are not connected to major health institutions and are unable to relocate to clinical sites due to disabilities, family, work, or social challenges, or other factors.
An added benefit of decentralized trials is the opportunity for sites to learn from each other and for sites with less expertise and capacity, especially those in less advanced countries, to take part and to increase their capabilities. For patients, of course, it would allow access in settings that would otherwise be excluded. For trialists, it allows the recruitment of patients with exactly the targeted requirements or with greater diversity, which can increase the validity and applicability of findings.
We urge the development of internationally agreed upon streamlined processes that will allow for simultaneous approval and implementation of decentralized trials across countries. We are especially concerned with the approach for cell and gene therapies, as well as other “durable” or “potentially curative” therapies that could have inordinate benefit in settings where health services are otherwise lacking
5. Based on your experience and knowledge, would the proposals in the Consultation Paper meet Health Canada’s goal of enabling innovative clinical trials in Canada?
From CORD’s perspective, “enabling innovative clinical trials in Canada” should not be a goal; it is an important but insufficient component toward the true end goal of “enabling Canadians (patients and public) timely and optimal access to health technologies that potentially diagnose, prevent, treat, and cure physical and mental health conditions.” To that end, innovation in clinical trials is less important than an approach to trials that is agile, adaptive, and inclusive of all stakeholders, especially the end users (patients and clinicians).
Moreover, it is important that an agile approach be initiated as “learning” pilots with draft conditions and guidelines, with process and outcomes assiduously documented, reviewed, and adapted, as appropriate.
From a patient perspective, we are very much “on board” to participate and to learn.
6. Are there innovations or other future considerations that Health Canada should account for when modernizing the clinical trials framework?
What are the major health and related trends that will impact health technologies and therefore affect clinical trials?
9. Are there other areas where burden can be reduced that will better enable your organization to conduct clinical trials without compromising patient safety?
Patient organizations rarely lead clinical trials research but they assume pivotal roles in all aspects and phases of trial design and implementation, including awareness, education, recruitment, retention, input on outcomes, monitoring, validation of findings, distribution of results, and use to support HTA and reimbursement process. These are indeed tremendously burdensome activities, especially for (rare disease) patient organizations with limited resources (human, time, and financial). Organizations use a variety of resources, including charitable donations, industry funding (often in the form of educational grants), donated human resources from a variety of experts, and volunteer time. In order for patient organizations to optimally contribute to the drug life-cycle from research and development to access, it is imperative for the federal government, provincial governments, other agencies to allocate funding directly to the patient organizations for their services.
10. Are there areas where Health Canada could go further in modernizing the Canadian clinical trials regulatory framework beyond what is proposed in the consultation paper?
Answered previously in Question (4) with respect to access to drugs not on indication, expanding indications for approved therapies, repurposed drugs, and multi-indication trials.
11. Do you see value in implementing a new policy and/or regulation for registration and reporting of results for clinical trials conducted in Canada, investigating drugs, medical devices and natural health products?
Internationally, there is growing consensus for “open pharma” to make information on clinical trials, including all results, fully accessible. Canada absolutely should implement policies and/or regulations that mandate registration and reporting of results of all clinical trials conducted in Canada (or those in which Canadian patients and clinicians take part regardless of where they are located) for all health technologies, including drugs, devices, and natural health products, as well as other trials that make health-related claims, including nutritional supplements, mental health, and quality of life. Health Canada should coordinate policies and/or regulations with international initiatives as well as support information (publications) being available in “plain language” and contributing to education to increase capacity for patients to effectively locate and use clinical trials reporting.
Health Canada should have a dedicated Canadian site reporting on “in Canada” trials as well as linkages to other reliable and valid sources of trials results.
RARE DISEASE DAY 2024 CANADIAN ILLUMINATIONS
On February 29, 2024 these monuments will be lit up in honor of Rare Disease Day. #LightUpForRare Amherst Town Hall in Amherst Nova ScotiaBrampton Clock TowerBritish Columbia LegislatureBritish Columbia PlaceCalgary TowerEdmonton High Level BridgeEdmonton TowerFred A. Lundy bridge in Newmarket, ONMississauga City HallNanaimo BastionNiagara Falls (10:00pm – 10:15pm.) [Live cam link: https://www.earthcam.com/canada/niagarafalls/?cam=niagarafalls_str]Niagara sign in Thorold/Niagara regionOakville Town HallOlympic Cauldron Vancouver Convention CentrePeterborough City HallSales Of Light VancouverScience World Vancouver (FEB 28th)Signal Hill in St. John’s, NLThe Hamilton SignToronto CN TowerToronto Sign in Nathan Phillips SquareVaughan City HallVancouver Convention CentreThe Peace Bridge between Canada and the US Winnipeg Sign Winnipeg Bridge Let us know if there are other Canadian illuminations to add. Tag us on social media @raredisorders (Twitter/X), @raredisorders_cord (Instagram) or email us at info@raredisorders.ca with your photos of the monuments and Rare Disease Day events.
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