Health Canada, through its Clinical Trials Database, is providing to the public a listing of specific information relating to phase I, II and III clinical trials in patients. The database is managed by Health Canada and provides a source of information about Canadian clinical trials involving human pharmaceutical and biological drugs. [from website]

Health Canada, through its Clinical Trials Database, is providing to the public a listing of specific information relating to phase I, II and III clinical trials in patients. The database is managed by Health Canada and provides a source of information about Canadian clinical trials involving human pharmaceutical and biological drugs.

Health Canada, through its Clinical Trials Database, is providing to the public a listing of specific information relating to phase I, II and III clinical trials in patients. The database is managed by Health Canada and provides a source of information about Canadian clinical trials involving human pharmaceutical and biological drugs.

BackgroundThis study examined multiple aspects about the approval of new drugs: the characteristics of the drugs, the quality and quantity of information that Health Canada discloses about the demographics of patients enrolled in clinical trials, the characteristics of the trial, and the type of review that it uses. It examines whether there have been changes in these measures between 1 September 2012 and 31 March 2022.MethodsA list of all new drugs approved, type of review used, and drug characteristics was generated from Health Canada annual reports. Therapeutic categories were identified from the World Health Organization Collaborating Center for Drugs Statistics Methodology. The Summary Basis of Decision documents of Health Canada were used to identify patient demographics in clinical trials and clinical trial characteristics.ResultsHealth Canada approved 326 new drugs for 407 indications. The percent of orphan drugs approved increased from 35.6 to 51.3%. The number of indications per drug decreased (p = 0.0817) as did the number of pivotal trials per drug (p = 0.0091). The percent of Phase 3 trials dropped from 76.3% in 2012–2015 to 64.8% in 2019–2022 (p = 0.005). There was also a statistically significant decrease in the percent of trials that were randomized, controlled, and blinded. The clinical trial characteristics of orphan drugs and the type of review used were both significantly different compared with non-orphan drugs. The percent of trials which had information about the number of patients enrolled, the percent of trials that provided the age of the patients, and the sex breakdown all significantly increased.ConclusionThe results show that there has been a change in regulatory standards that may be due to them becoming less rigorous, because of an adaptation to the number of orphan drugs being submitted or a combination of both reasons. At the same time, there has been some improvement in the transparency of data. Health Canada has recently embarked on a series of reforms in drug regulation and clinical trial management. These changes need to be closely evaluated to be sure that they enhance the efficacy and safety of new drugs.

Health Canada's Clinical Trials Database is a listing of information about phase I, II and III clinical trials in patients. The database is managed by Health Canada and provides a source of information about Canadian clinical trials involving human pharmaceutical and biological drugs. Additional information on Health Canada’s CTD is available at: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/health-canada-clinical-trials-database/frequently-asked-questions.html

Objectives: This study examines the characteristics of studies that Health Canada uses to grant full marketing authorization for products given a conditional approval between January 1, 1998 and June 30, 2017.

Design: Cohort study.

Data sources: Journal articles listing drugs that fulfilled their conditions and received full marketing authorization, Notice of Compliance database, Notice of Compliance with conditions web site, Qualifying Notices listing required confirmatory studies, clinicaltrials.gov, PubMed, Embase, companies making products being analyzed, journal articles resulting from confirmatory studies.

Interventions: None

Primary and secondary outcome measures: Characteristics of studies - study design (randomized controlled trials, observational), primary outcome used (clinical, surrogate), blinding, number of patients in studies, patient median age, number of men and women.

Results: Eleven companies confirmed 36 publications for 19 products (21 indications). Twenty-nine out of the 36 studies were randomized controlled trials (RCTs) but only 10 stated if they were blinded. Twenty used surrogate outcomes. The median age of patients was 56 (interquartile range (IQR) 44, 61). The median number of men per study/trial was 184 (IQR 58, 514) versus women - 141 (IQR 46, 263).

Conclusions: Postmarket studies required by Health Canada had more rigorous methodology than those required by either the Food and Drug Administration or the European Medicines Agency. There were still deficiencies in these studies. The absence of blinding in the majority of RCTs may introduce bias in their results. The use of surrogate outcomes especially in oncology trials means that improvements in survival are not available. The relatively young age of patients, even for products for cancer, means that predicting how the elderly will respond is often unknown. The almost universal finding that men outnumbered number women may make it hard to differentiate responses by sex. These results raise potential concerns about the quality of evidence that Health Canada accepts.

Health Canada has authorized certain clinical trials in patients in Canada. Our public Clinical Trials Database is a public listing of specific information relating to these trials. Additional publicly accessible registries that further support finding suitable trials are: ClinicalTrials.gov and Current Controlled Trials International Standard Randomized Controlled Trials Number Register.

The table below lists the clinical trials authorized by Health Canada for COVID-19-related medical devices. Authorization is done through the Medical Device Regulations or the Interim Order No. 2 for clinical trials for medical devices and drugs related to COVID-19.

Health Canada (HC) and the Canadian Institutes of Health Research (CIHR), with the collaboration and participation of the Canadian Association of Research Ethics Boards (CAREB), recognize the urgent need to conduct clinical trials to evaluate the safety and efficacy of a drug, a vaccine or a medical device in treating, preventing, mitigating or diagnosing COVID-19.

The Food and Drugs Act and the Food and Drug Regulations govern the sale and importation of drugs for use in human clinical trials in Canada. This document provides guidance on the regulatory obligations pursuant to Part C, Division 5 of the Regulations, Drugs for Clinical Trials Involving Human Subjects.

Manufacturers of medical devices intended to treat COVID-19 can choose between 2 different processes to apply for a trial authorization: process for investigational testing outlined in the Medical Devices Regulations or process outlined in the new interim order for clinical trials for medical devices and drugs related to COVID-19.

Sponsors of COVID-19-related drug and vaccine clinical trials can choose between 2 different processes: existing process outlined in the Food and Drug Regulations or process outlined in the new interim order for clinical trials for medical devices and drugs related to COVID-19.

Depending on the type of clinical trial, sponsors may be required to file a Clinical Trial Application (CTA) for human drug clinical trials. Instances where a CTA must be filed are summarized in the chart below.

Guidance documents for management of drugs for clinical trials involving human subjects. The sponsor must ensure that the clinical trial is conducted in accordance with the requirements of the protocol, which has been authorized by Health Canada and approved by REB(s).

This statement provides guidance to clinical trial applicants about the investigational use of marketed drugs within clinical trials in Canada.

The purpose of this notice is to advise stakeholders that Health Canada is proposing to: maintain the flexibilities and regulatory oversight provided by the Interim order respecting clinical trials for medical devices and drugs relating to COVID-19 until at least the fall of 2021, and bring forward regulatory amendments that would allow the flexibilities under the Interim Order to continue after the fall of 2021

The tables below list the COVID-19-related clinical trials which have been authorized by Health Canada through the Food and Drug Regulations or the Interim order No. 2 for clinical trials for medical devices and drugs related to COVID-19.

During the COVID-19 pandemic, Health Canada is working closely with domestic and international partners to anticipate and meet Canadians' health product needs. This involves discussing, collaborating and leveraging resources on issues related to clinical trials and investigational testing, drug and medical device market authorizations, health product risk assessments, and potential drug and medical device shortages.

The table below lists the clinical trials authorized by Health Canada for COVID-19-related medical devices. Authorization is done through the Medical Device Regulations or the Interim Order No. 2 for clinical trials for medical devices and drugs related to COVID-19.

This manual is based on Health Canada's Guidance for Clinical Trial Sponsors: Clinical Trial Applications and other applicable guidance documents. It is designed to provide tools and relevant links in order to facilitate the successful filing of a Clinical Trial Application (CTA) to Health Canada.