Un couloir d'hôpital.
Un couloir d'hôpital.
A Highly Regulated Process

Detailed Oversight Process for Clinical Trials

Different provincial, national and international regulations govern, in turn, how clinical trials are authorized, conducted, completed or suspended. If the results of the clinical trials are positive, federal and provincial authorizations are also required to make the new treatment available to the public.

Authorizations Required Before a Clinical Trial

Authorizations Required Before a Clinical Trial

Any application for a clinical trial in Canada must first be approved by Health Canada. A regulatory file must be submitted to Health Canada before the start of the clinical trial. This file contains, among other things, the research protocol and information related to the manufacture and safety of the treatment.

Before being authorized, each clinical trial also undergoes a triple review for ethics, scientific validity and suitability.

Scientific review

The scientific review is conducted by experts in the same field of research who examine the scientific validity of the clinical trial.

Ethics review

The ethics review is conducted by a research ethics board (REB) that reviews all relevant clinical trial documents, particularly those that will be presented to participants.

The REB ensures that the clinical trial meets the three guiding principles of Ethical Conduct for Research Involving Humans:

  • Respect for individuals: Includes the dual duty of the REB to ensure that participant autonomy is respected, and that people whose autonomy is developing, hindered or diminished are protected. The obligation to seek free, informed and ongoing consent is one of the mechanisms to ensure respect for individuals.
  • Concern for well-being: research teams and REBs must strive to protect or promote participant well-being when there are foreseeable risks associated with the research. This is done by ensuring, among other things, that participants are not exposed to unnecessary risks. Concern for well-being also applies when research is likely to have implications for the well-being of particular groups outside the study or for society as a whole.
  • Justice: Refers to the obligation to treat people fairly (treating people with the same level of respect) and equitably (trying to ensure a fair distribution of the advantages and discomforts of participation and the benefits of knowledge). This highlights the importance of paying particular attention to vulnerable (children, pregnant women) or marginalized (certain ethnocultural communities) individuals or social groups.
Institutional feasibility review

A suitability review is conducted by the health facility where the clinical trial will take place. The purpose of this review is to make sure that the facility has the physical and human resources needed to conduct the clinical trial. It also looks at the specifics of each project (priorities, relevance...).

Oversight During the Clinical Trial

Oversight During the Clinical Trial

Once the clinical trial has been authorized, it is implemented at one or more institutions (or sites). Participants are then recruited based on the authorized research protocol.

During the study, the trial is regularly reviewed by various types of committees, including, for example, a Data and Safety Monitoring Board (DSMB), which is responsible for periodically evaluating the conduct, data and results of the trial to ensure participants’ safety. If adverse effects appear over the course of the project, they are reported to different authorities (REB, Health Canada, etc.) which informs their decision on the need to suspend or discontinue the study.

Review After the Clinical Trial

Review After the Clinical Trial

At the end of the clinical trial, the anonymous data collected is analyzed by the sponsor. During this step, the sponsor can decide:

  • If the results are promising and, therefore, if evaluation of the study treatment can continue in the next phase (in the case of a Phase I or II clinical trial).
  • If the treatment has been efficacious and can be submitted to Health Canada for approval, so that it is eventually available to the public (in the case of a Phase III clinical trial).

The findings of the clinical trial are also reported as a scientific article in a specialized medical journal. Before publication, the article is reviewed by other scientists in the same field of research. These specialists assess the quality of the approach and the scientific rigour of the clinical trial before authorizing publication.

The results are published, but the participants in the clinical trial remain anonymous.

Discontinuation of a Clinical Trial

Health Canada, the ethics committee or the sponsor can discontinue a clinical trial at any time. Although this rarely happens, the trial can be discontinued if one or more unexpected severe side effects are observed, or if the efficacy of the treatment has not been demonstrated. Sometimes, the number of people recruited for the clinical trial is too small for the study to continue.

When a clinical trial is discontinued, the research team informs the participants as soon as possible and tells them what the next steps are.

Public Access to the Treatment

Canadian Authorization

If the results of the clinical trials show that the study treatment is efficacious and safe, the manufacturer can apply to Health Canada for a market authorization to put the treatment on the Canadian market. As part of this process, Health Canada evaluates, among other things, the results of the preclinical and clinical trials, as well as details regarding the treatment’s production, packaging and labelling.

If all the information is considered satisfactory, Health Canada issues a Notice of Compliance and a Drug Identification Number (DIN) authorizing the prescription of the treatment in Canada. If the review concludes that there is not enough evidence to prove that the treatment is safe and efficacious, a market authorization will not be granted, and the treatment will not be authorized in Canada.

The Health Canada authorization process typically takes 6 months to 2 years.

Provincial Review

The mandate of the Institut national d’excellence en santé et en services sociaux (INESSS) includes assessing applications for the listing of drugs, blood products and medical devices in order to make recommendations to the Minister of Health. The Minister of Health makes a decision based on the recommendations, and Régie de l’assurance maladie du Québec (RAMQ) puts the payment in place.

Drug evaluation by INESSS

INESSS carries out its drug evaluation mandate based on the five aspects provided in Section 7 of its act of incorporation. INESSS conducts an overall evaluation of the value of the treatment, including its clinical benefits (therapeutic value) and economic benefits (pharmacoeconomic value) to ensure optimal use of resources in the health and social services sector. The information is based in part on the findings of the clinical trials submitted by the manufacturer.

Any interested person or group (including clinical specialists, patient organizations and the public) can submit comments and opinions on a drug that is subject to an INESSS evaluation.

Based on this evaluation, INESSS may or may not recommend to the Minister of Health that the health product or device be listed on the public drug plan formulary for a given therapeutic indication.

In most cases, this leads to price negotiations across Canada, and the Minister of Health lists the health product or device in the public drug plan formulary, if applicable. INESSS sets out the payment criteria (also known as reimbursement criteria) that will be managed by RAMQ or by health facilities.

Each year, INESSS evaluates more than 100 promising drugs. The list of drugs under evaluation is available on the INESSS website.

Aligned Review Process (CADTH/INESSS/Health Canada)

Aligned Review Process (CADTH/INESSS/Health Canada)

Canada’s Drug and Health Technology Agency (CADTH), Institut national d’excellence en santé et en services sociaux (INESSS) and Health Canada work together to provide timely access to drugs and medical devices. As part of the aligned drug review process, the three organizations can assess manufacturers’ submissions almost simultaneously when they have received the authorization to do so.

This process reduces the time between Health Canada’s Notice of Compliance and INESSS recommendations. The aligned review process does not change the respective requirements, decision-making or processes of Health Canada and INESSS. Visit this site to learn more about the aligned review process.

Access to the Public

Once the Minister of Health authorizes the enrolment of a treatment in the public plan, Régie de l’assurance maladie du Québec (RAMQ) will cover accessibility and part or all of the costs of the treatment for the public.

If the Minister of Health refuses to evaluate the treatment, it will not be listed in the public plan and will not be covered by RAMQ.

Special Access Program (Before Authorization by Health Canada)

Special Access Program (Before Authorization by Health Canada)

Health Canada’s Special Access Program (SAP) allows healthcare professionals to request access to drugs or medical devices that are not yet available for sale in Canada. This program targets humanitarian situations or emergencies, for example, in cases where people have serious medical conditions or where standard treatments are not available.

Under the SAP, the manufacturer generally covers the cost of the drug or medical device to provide it to those for whom the special access request was made.

Learn more

Exception Drugs and Exception Patient Measures (Following Health Canada Authorization)

Un médecin en blouse blanche tenant un médicament.

Exception Drugs and Exception Patient Measures (Following Health Canada Authorization)

The listing of a health product or device as an "exception drug" allows anyone wishing to obtain coverage for certain drugs, usually not covered, to obtain coverage under certain conditions and if the latter are used in compliance with the indications recognized for their payment by the INESSS.

For example, a psoriasis cream, usually not covered, may be covered as an exception drug in the event that the use of another treatment (as determined by the INESS) is insufficient for people suffering from the medical condition.

The “exception patient” measure is used in exceptional situations to cover the cost of drugs not included on the list of authorized drugs. The measure can also be used to cover the cost of exceptional drugs prescribed for a therapeutic indication other than the one prescribed on the INESSS list.

For both types of access, a healthcare specialist must make a prior authorization request.

Learn more about RAMQ access measures (FR)