What we heard: Draft guidance on expanded access clinical trials

Purpose

The Draft guidance on expanded access clinical trials was published on August 2, 2024, and opened to the public for consultation until October 31, 2024.

This "what we heard" report:

provides background and context for the draft guidance
summarizes the consultation approach and
gives an overview of the comments we received

Background

Policy intent

Health Canada developed the Draft Guidance on Expanded Access Clinical Trials to facilitate access to drugs that have not yet been authorized or are not available in Canada. These include drugs for certain patients with serious or life-threatening conditions where authorized alternatives may be limited (for example, oncology, rare diseases, some mental health disorders and pediatric medicine).

Expanded access clinical trials are another way for patients with unmet medical needs to access unauthorized products through a clinical trial. This type of clinical trial is separate and distinct from the Special Access Program (SAP).

Choice of regulatory instruments

Expanded access clinical trials are a type of clinical trial. They are regulated and authorized under Part C, Division 5 of the Food and Drug Regulations, drugs for clinical trials involving human subjects. They provide access to investigational drugs that have the potential to treat people living with medical conditions who do not qualify for other clinical trials or are not able to participate in one.

An advantage of the clinical trial regulatory framework is that access can be provided in accordance with good clinical practices and good manufacturing practices. These principles are meant to protect the rights, safety and well-being of participants.

Expanded access clinical trials have been authorized by Health Canada in the past and continue to be authorized when they meet the requirements set out in the regulations. Providing guidance on how to meet these requirements is intended to help sponsors face fewer barriers in launching expanded access clinical trials and give patients in need more opportunities for access.

Alignment with other modernization initiatives

Health Canada is modernizing Canada's clinical trials framework (Clinical Trials Modernization Initiative) to facilitate more decentralized models for all types of clinical trials.

The draft guidance describes how a decentralized, delegated model could allow qualified investigators to conduct expanded access clinical trial activities (such as administering treatment) without having to open a new clinical trial site. A decentralized model has the potential to expand the geographic reach for all types of clinical trials.

We will develop next steps for expanded access based on the feedback we received during this consultation. The comments will also help us modernize the wider regulatory framework for all clinical trials.

Learn about the Clinical Trials Modernization Initiative.

Consultation approach

Interested parties were invited to submit comments and feedback on the draft guidance. We reached out to interested parties in 3 ways:

website:
- published the draft guidance online along with a consultation page, which outlined how to submit comments
stakeholder registry:
- contacted groups that had joined our stakeholder registry
- groups included academia, research organizations, industry, advocacy groups, health facilities and licensed practitioners
webinars:
- hosted 2 sets of information webinars on the draft guidance in both official languages on September 12 and September 24, 2024
- gave an overview of the draft guidance, explained the regulatory requirements for expanded access clinical trials and held a question-and-answer session
- over 150 people attended

We received 21 submissions with comments on the draft guidance from 6 different types of groups:

pharmaceutical companies: 9 submissions
clinical trial organizations: 4 submissions
patient advocacy organizations: 4 submissions
research hospitals: 2 submissions
pharmaceutical industry associations: 1 submission
psychedelics advocacy organizations: 1 submission

Key themes

The comments we received represent a range of views. Some groups support the draft guidance and the concept of expanded access clinical trials. For example, they cited the benefits of decentralized models and expanding access to more diverse population groups. Others said there are potential barriers to using clinical trials to provide expanded access, as well as wider challenges with the current clinical trial regulatory framework.

We divided the comments into 5 key themes:

Clarifying policy objectives
Aligning with other regulators
Barriers to uptake under a clinical trial model
Patient participation and engagement
Benefits of decentralization

Theme 1: Clarifying policy objectives

In the draft guidance, expanded access under the clinical trial framework includes strict regulatory requirements and standards associated with how the trial is conducted, participant safety and overarching research objectives. Many respondents said this may be at odds with the main policy objective, which is to help patients with unmet medical needs access unauthorized or otherwise unavailable drugs.

Conducting clinical trials in Canada requires extensive logistics and administration. Some respondents considered that it may be overly complex and it may be easier to facilitate expanded access under a different framework. For example, local health facilities that play a role in a clinical trial must comply with procedures established in the clinical trial protocol. This may not align with local best practices or the treatment needs of individual patients. If the main goal is to treat patients, health care providers should be able to determine their own treatment standards and not be restricted to a clinical trial protocol.

Respondents pointed out the challenge in tying expanded access to the requirement to generate data and evidence. Some respondents did not agree that information collected through expanded access clinical trials may contribute to useful real-world evidence. They questioned the value of this evidence outside of the study and how it will be evaluated by the regulator or incorporated into labelling. There's also a risk that data from expanded access clinical trials could be used to supplement ambiguous trial data, which can affect the perceived efficacy of the drug.

Given these points, some respondents said that Health Canada should focus on supporting patient access rather than generating evidence. They said that expanded access should be more patient-focused and not regulated under the clinical trials framework.

Health care providers can use SAP to request access to unauthorized drugs to treat a patient with serious or life-threatening conditions when conventional therapies have failed, are unsuitable or are not available. Unlike expanded access clinical trials, which have overarching research objectives, SAP gives exceptional access to unauthorized drugs for patients in an emergency medical situation.

Some respondents are concerned that Health Canada may limit access through SAP and redirect requests to expanded access clinical trials. This would create problems for sectors that rely heavily on SAP (for example, pediatrics). Expanded access clinical trials are designed to facilitate access, not restrict or influence access made through programs or other avenues like SAP.

Theme 2: Aligning with other regulators

The United States has an expanded access program that offers multi-tier access to investigational drugs for individuals and groups. Some respondents are concerned that using the words "expanded access" to refer to a type of clinical trial in Canada could create confusion. A misalignment in regulatory requirements compared to U.S. expanded access programs could also hamper companies from offering their existing U.S.-based expanded access programs to patients in Canada.

Another concern is that some of the requirements related to clinical trials in Canada do not align with those of other regulators. For example, unlike the U.S. Food and Drug Agency or the European Medicines Agency, Health Canada requires sponsors to submit a Clinical Trial Site Information Form before starting or amending a clinical trial protocol. This is not a requirement in other jurisdictions. Not being in alignment with other regulators can cause confusion and make it harder to conduct clinical trials in Canada, thus deterring companies from conducting an expanded access clinical trial in our country.

Health Canada is exploring some of these issues through our initiative to modernize the Canadian regulatory framework for the oversight of clinical trials involving drugs.

Theme 3: Barriers to uptake under a clinical trials model

Barriers for sponsors

Clinical trials carry a financial, administrative and regulatory burden. A modernized regulatory framework for clinical trials in Canada could relieve some of this burden in some cases, but would not address all the comments received.

Examples of financial burden:

Sponsors who conduct other types of clinical trials may not have the financial resources to start an expanded access clinical trial, due to the high cost of clinical trials.
Decentralizing trial activities will reduce some of the work involved in opening additional trial sites and make it possible to delegate some tasks to qualified individuals outlined in the trial protocol. However, many health care providers do not have the resources to take on these tasks. They may need to be compensated financially by the sponsor, which will add to the financial burden.

Given these issues, sponsors and health care providers may be pressured to divert resources away from other areas, including other clinical trials, to conduct an expanded access clinical trial. This goes against the requirement that expanded access clinical trials not hinder clinical development.

Respondents said that these financial concerns would need to be addressed if we are to provide effective and meaningful patient access to investigational drugs in Canada under a clinical trial framework.

Examples of administrative and regulatory burden:

Expanded access clinical trials offer some flexibility when it comes to trial objectives and eligibility criteria. However, because the Division 5 regulatory requirements still apply, the administrative and regulatory burden is high. This includes requirements related to the clinical trial application, review periods, good clinical practices, inspections and monitoring, approvals related to controlled substances and Clinical Trial Site Information Forms. Increased costs can make it difficult to attract international trials.
Health Canada should consider whether the goal of providing expanded access to unauthorized or unavailable drugs for people in Canada is aligned with the regulatory burden of the clinical trial framework. Perhaps a different type of program could more clearly align with policy objectives.

Barriers for potential participants

Accessibility of clinical trial information:

Some clinical trial websites, including sponsor sites and the Government of Canada's Clinical Trials Database, are difficult to navigate. Finding key details such as the sponsor's contact information may not always be straightforward. The language can be too technical for the general public.
As this information is mainly online, some people such as Indigenous People living in rural and remote communities may not have reliable access to these resources. This can add to the inequities that already exist in seeking access to health care.

Lack of access to health care providers and facilities:

Many people in Canada do not have a family doctor. The burden to find a clinical trial is often placed on potential participants. Without a health care provider to give them medical advice, they may not be able to find an appropriate clinical trial and assess its benefits and risks.
Access to clinical trials often depends on how close the potential participant is to a health facility that can perform the necessary tasks outlined in the protocol. This could cause enrolment delays, which in turn could result in someone who was once eligible being disqualified because their disease had progressed too far by the time they accessed an appropriate facility.
These barriers may be especially challenging for marginalized or equity-seeking communities, such as Indigenous Peoples and people living in rural and remote areas, who may not have access to health care services and clinical trial sites.

Theme 4: Patient participation and engagement

Some respondents stressed the importance of informed consent. Potential participants should fully understand the trial's objectives, and clear communication should happen early and consistently to manage expectations.

One interested party questioned how to reconcile the concept of "informed consent," as described in the clinical trial framework, and the concept of "free, prior, and informed consent" for Indigenous Peoples. This point raised several questions about how to encourage the participation of Indigenous Peoples and Indigenous sponsors in clinical trials.

To this point, respondents recommend that we:

clarify training and education requirements for Indigenous Peoples who are involved in organizing clinical trials and non-Indigenous sponsors looking to work with Indigenous Peoples and communities
consider indemnity coverage for Indigenous people who are already disadvantaged by inequities in the health care system
seek and obtain prior approval through local and territorial groups before undertaking research on Indigenous land or with Indigenous participants and
make sure that personal health data is properly collected, stored and used

Theme 5: Benefits of decentralization

In general, respondents supported decentralized models in clinical trials and said there are benefits to providing access to more participants, including Indigenous people and other underrepresented or equity-deserving groups.

Broader eligibility criteria or a range of settings could make it possible to enroll more people in clinical trials, giving them access to investigational drugs and increasing the sample size for sponsors. Sponsors could also have more diverse participants and participation in a decentralized clinical trial could be more accessible and equitable.

Next steps

We will continue to analyze all the feedback and comments, including the requests for clarification we received from interested parties. Our analysis will help us develop next steps for enabling expanded access and related timelines for finalizing the draft guidance.

At the same time, we will be advancing the clinical trials modernization initiative to ensure that the Canadian clinical trials framework meets the needs of sponsors and participants.

Contact us

For questions about the contents of this report or next steps, contact Health Canada's Bureau of Policy, Science, and International Programs:

Bureau of Policy, Science and International Programs
Pharmaceutical Drugs Directorate
Health Products and Food Branch
Health Canada
1600 Scott St, Holland Cross - Tower B
Address Locator: 3106B
Ottawa ON K1A 0K9
Email: bpsip-bpspiconsultation@hc-sc.gc.ca

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Date modified:: 2025-02-11

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