Draft guidance on expanded access clinical trials: Information for potential participants and health care providers

On this page

• General considerations
• Benefits and risks
• How sponsors initiate expanded access clinical trials
• Finding, joining and participating in a clinical trial

General considerations

Clinical trials are investigations that help advance medical knowledge, to try and find out whether a drug is safe and effective in humans for a specific disease or condition. They are essential to develop scientific evidence about a therapeutic product that can potentially improve the quality of life for people living with a disease or condition.

Clinical trials are conducted in phases and progress from exploratory trials to confirmatory trials. Exploratory clinical trials (phases 1 and 2) test the initial effects of a drug in a small number of participants. Confirmatory (phase 3) trials generate statistically conclusive evidence of the drug's efficacy and safety by testing it in larger groups. Evidence from clinical trials is then used to seek authorization from Health Canada to market the drug in Canada.

People living with a medical condition or disease who participate in a clinical trial may benefit from having access to a drug that may cure or control their condition or improve their quality of life.

While clinical trials may provide access to an investigational drug for some participants, their main purpose is to answer a specific research question. To achieve this objective, clinical trials must be rigorously designed with appropriate measures (for example, by setting criteria for who can participate or by giving some participants a placebo). This may result in certain potential participants living with medical conditions being excluded from a clinical trial or from receiving the drug as part of a trial. Therefore, participation in a clinical trial does not always result in a participant gaining access to the investigational drug.

Expanded access clinical trials are a type of clinical trial designed to facilitate access to investigational drugs to people living with medical conditions who may be expected to benefit from the drug and cannot participate in other clinical trials. Although one of the objectives is to facilitate access for treatment use, like all clinical trials, access to the investigational drug in expanded access clinical trials:

• is part of the overall investigational plan, which is intended to achieve the following:
  • discover or verify the drug's clinical, pharmacological or pharmacodynamic effects
  • identify any adverse events from the drug
  • study the drug's absorption, distribution, metabolism and excretion properties or
  • assess its safety or efficacy
• includes the monitoring of outcomes and the collection of related data

In general, expanded access clinical trials have broader research objectives, such as long-term safety and effectiveness. They can aim to gather information about rare side effects that may only become evident in an expanded participant population.

Despite the expanded inclusion criteria, it's possible that some people may still not be able to gain access to an investigational drug through an expanded access clinical trial.

Benefits and risks

Like all drugs, drugs used in clinical trials come with possible benefits and risks. In general, there is less information about the efficacy and safety of an investigational drug being studied in a clinical trial compared to a drug that Health Canada has reviewed and authorized for sale.

Evidence to demonstrate a drug's safety and efficacy can vary depending on whether it's in the early or later phase of development. The drug may ultimately prove to be of no benefit to a particular participant or may be associated with unexpected and serious adverse effects. Only some drugs that begin clinical trials eventually seek market authorization.

After considering treatment options that are available on the market, people with medical conditions may choose to explore investigational drugs as potential treatments for their condition.

Potential participants who wish to enrol in an expanded access clinical trial to gain access to an investigational drug should discuss the risks and potential benefits with their health care provider. For all clinical trials, including expanded access clinical trials, the Food and Drug Regulations (regulations) require that the health and safety risks and potential but unconfirmed benefits be clearly communicated to potential participants. Potential participants must give their informed consent before they can be enrolled in a trial.

Learn more:

• Informed consent
• Clinical trials and drug safety

How sponsors initiate expanded access clinical trials

There is no requirement for a drug manufacturer to provide access to their investigational drug through an expanded access clinical trial. Health Canada cannot compel a drug manufacturer to do so.

Sponsors (usually the drug manufacturer) may initiate expanded access clinical trials when there's an identified need for people living with medical conditions who are unable to participate in ongoing clinical trials. Sponsors develop a protocol that outlines the investigational plan. This plan includes criteria for patient eligibility, treatment administration, monitoring outcomes and participant safety, and collecting data. The sponsor then submits this protocol to Health Canada for review by filing a clinical trial application (CTA).

Health Canada reviews CTAs for expanded access clinical trials like any other clinical trial. We review the information to make sure that:

• the investigational drug will be used in a safe way for the proposed participants and
• any health and safety risks associated with the drug will be addressed appropriately

For expanded access clinical trials, we review evidence provided by the sponsor from previous clinical trials or other studies. The sponsor must demonstrate that the proposed use of the investigational drug, in the proposed expanded population, is evidence-based and adequately identifies, addresses and discloses risks to prospective participants.

Sponsors of expanded access clinical trials must also provide specific information in their CTA that will allow us to thoroughly assess the risks of the trial. Some of these requirements and their impact on potential participants are listed in Table 1.

Table 1: Requirements for expanded access clinical trials and impact on potential participants

Specific requirements	Impact on potential participants
Sponsors must provide information on why providing access to an investigational drug for an expanded population outweighs any possible risks. For example, sponsors can provide information on the: severity of the condition lack of available therapeutic alternatives possible increase in benefits or decrease in risks compared to existing authorized products	Potential participants may be: required to be diagnosed with a certain condition to be included required to have tried other available alternatives or excluded based on safety reasons (for example, potentially dangerous interactions with other drugs) Expanded access clinical trials may not be appropriate for certain drugs.
Sponsors must provide information on whether the expanded access clinical trial will affect participation in a confirmatory trial. For example, a sponsor may: delay enrolment in an expanded access clinical trial until phases 1 to 3 trials have completed enrolment define inclusion criteria for the expanded access clinical trial based on exclusion criteria from other ongoing confirmatory trials	Potential participants who qualify for an ongoing clinical trial may: not be permitted to enrol in an expanded access clinical trial be invited to enrol in an ongoing clinical trial instead Participation in clinical trials is always voluntary.

If the CTA meets the regulatory requirements, Health Canada issues a 'no objection' letter to the sponsor within the review period of 30 days. The clinical trial site must also be approved by a research ethics board, and the approval filed with Health Canada, before the sponsor can begin enrolling participants at the site.

Finding, joining and participating in a clinical trial

How to find a trial

People living with medical conditions can search Health Canada's Clinical Trials Database for information about all clinical trials that have met regulatory requirements. This includes the status of any expanded access clinical trial for a certain medical condition or a specific drug product.

Potential participants may find a potential expanded access clinical trial for their condition by, for example, searching for their medical condition. They may contact the sponsor directly to start the screening and enrolment process. The sponsor of the clinical trial should also be contacted for more information about a trial's objectives, patient enrolment criteria, potential clinical trial sites and to confirm the status of the trial.

Health Canada does not sponsor or design clinical trials, and the database is not a patient recruitment tool. Individuals who want more information on clinical trials found in the database should speak with their health care provider and contact the clinical trial sponsor.

Information made public by sponsors (for example, through a website) should make it possible for potential participants or their health care provider to contact the trial sponsor about enrolment.

If there isn't an expanded access clinical trial for a specific drug or condition, potential participants or their health care provider could contact a drug manufacturer to ask them to consider initiating one.

Find information on clinical trials in the Clinical Trials Database.

Joining a trial

A sponsor sets out the eligibility criteria for enrolling in an expanded access clinical trial. Potential participants may be excluded due to potential safety risks posed by existing conditions or dangerous interactions with other drugs, or if they have not tried other available treatments. Sponsors establish these criteria to mitigate the risks posed by the investigational drug.

After the sponsor of the expanded access clinical trial has been contacted, potential participants are screened for enrolment. The sponsor makes the final determination on who is enrolled in an expanded access clinical trial, based on the eligibility criteria.

In some cases, the investigator responsible for the trial may be required to invite potential participants to enrol in ongoing confirmatory clinical trials first, before they can be considered for enrolment in the expanded access clinical trial. Enrolment in a different clinical trial instead of the expanded access clinical trial could potentially also give participants access to the investigational drug.

Giving informed consent

To participate, sponsors must ask potential participants who are deemed eligible for an expanded access clinical trial to provide their informed consent. The trial's qualified investigator must obtain and keep a record of this consent.

Informed consent means that a potential participant is willing to participate in a specific trial, after having been fully informed about the trial and given the opportunity to ask questions. The process of obtaining consent usually involves a face-to-face meeting or communication between the qualified investigator or delegated third party and the potential participant.

In some cases, the sponsor may be able to justify conducting the process through a virtual meeting platform. This should take place in real-time and face-to-face, using both audio and video.

Before agreeing to participate in any clinical trial, potential participants should consider if they:

• are fully informed of all aspects of the trial that are relevant to their ongoing decision to participate, including potential indemnity coverage if they are harmed during the trial
  • this is documented in an informed consent form (ICF) (developed by the sponsor and reviewed and authorized by a research ethics board)
• know who to contact if they have questions about the research or how to end their participation in the clinical trial
• have a 24-hour contact number or know who to contact if they experience a research-related injury (for example, local health care provider, qualified investigator, research personnel)
• know who will have access to their personal health information collected during the study and how it will be stored
• have a written record of their informed consent, which the qualified investigator should also retain

People with medical conditions, in consultation with their health care provider, should carefully consider and weigh the:

• potential benefits and risks of an unapproved investigational drug and
• possible harms and inconveniences of participating in a clinical trial

Health care provider participation

Health care providers who agree to undertake activities delegated by the expanded access clinical trial's qualified investigator (such as administering the investigational drug, monitoring participants and collecting data) are conducting clinical trial activities.

Health care providers who participate in an expanded access clinical trial should verify that:

• their roles, responsibilities and liabilities are specified in an agreement (such as the clinical trial protocol or through additional contracts)
• the clinical trial site where the qualified investigator runs the trial has received approval by a Canadian research ethics board

Additional clinical trial site information (CTSI) forms and additional research ethics board approval are not required for physical locations that are added to an existing clinical trial site. An example would be adding a health care provider's office where activities that are delegated by the qualified investigator are to be conducted.

These activities must be clearly defined in the trial protocol and appropriately recorded in the trial's delegation log. Ultimately, the qualified investigator is responsible for medical decisions taken in relation to trial activities, wherever those activities (delegated or not) have occurred.

Health care providers connected to a different institution than the qualified investigator should be aware of local and institutional policies and requirements that may apply to their activities at their institution. In other words, third parties may have additional responsibilities under a local or institutional research ethics board.

Health care providers who have the legal ability to sponsor a clinical trial in Canada could offer to sponsor an expanded access clinical trial or to open a new clinical trial site as part of an existing expanded access clinical trial. The manufacturer may consider requests to provide a supply of the investigational drug for an expanded access clinical trial or an additional clinical trial site, but there's no legal requirement for the manufacturer to do so.