March 2022: Canada update

The article “Pharma is still burying clinical trial results in Canada, new study warns” has been published on March 23, 2022, on TranspariMED.

According to the Canadian research team, Canada lacks regulatory requirements as some pharma companies continue to prevent clinical trial results from being made public. Trials that showed harm or safety concerns were not published.

Health Canada and research institutions in Canada have an obligation to ensure that site investigators are able to report trial findings based on all data from multisite trials, when sponsors and trial leaders do not proceed with timely reporting.

The World Health Organization recommends that “Legislation or supporting regulations [should include] sanctions if a clinical trial is not registered and/or results are not reported.” The WHO has long demanded that the results of all interventional clinical trials be made public on a registry within 12 months of trial completion.

The Canadian study identified seven key themes related to industry influence on clinical trial reporting:

  1. Sponsor influence on decision-making about whether to publish
  2. Weaker incentives to publish trials with negative findings or evidence of harm
  3. Stopping trials early and not reporting stopped trials
  4. Ownership and control of data
  5. Clinical trial agreements and confidentiality restrictions
  6. Nonpublication of internal company trials
  7. Dependency on funding from industry-sponsored trial

 

February 2022: Canada Update

As a part of the regulatory modernization process, Health Canada had published a consultation paper in May 2021. Health Canada gathered feedback from stakeholders on the consultation paper through an online questionnaire, email submissions, and interactive webinars. Overall, 122 written submissions and close to 1000 stakeholders participated in webinars.

The respondents agreed with the proposals to modernize the clinical framework. Health Canada posted “What we heard: an executive summary” on their portal on February 23, 2022.  One of the topics in the post was transparency. Most respondents saw value in the new transparency policy/ regulation for registering trials and reporting results. Support from the academic community was 73% and that from the industry was 54%.

Registration:

Most respondents (86%) register their trials with an international registry like ClinicalTrials.gov. Some use the EU Clinical Trial Register and 1 respondent recommended ISRCTN.  For device trials, EUDAMED will be also be used once it becomes a law.

Feedback suggested that academic researchers have challenges in keeping their international registration up to date as compared to the industry researchers. The major challenge included the burden of being required to use multiple registries in different countries for multinational trials. Other challenges included resource requirements to keep up-to-date registry information and some registries being not user-friendly.

Public disclosure of results:

Most respondents (73%) report trial results in the international registries. Respondents explained that reporting results is a part of their good clinical practices and some explained that reporting is an international, research ethics board or publication requirement. Of the 27% of respondents who were contract research organizations (CROs) said they do not report their results. Most of them said it is the sponsor’s responsibility. Some (20%) who do not report their results on international registries said they publish results on their company websites.

The detailed information can be found here.

February 2022: Canada Update

Canadian Institutes of Health Research (CIHR) shared their policy guide on the requirements for the registration and disclosure of results from clinical trials on February 08, 2022.

The policy focuses on the registration of clinical trials and making them publicly available, free to access before the first visit of the first participant.

The following new requirements will be applicable to all clinical trials funded on or after January 01, 2022:

  • Publications including clinical trial results must be open to access from the date of publication.
  • Summary of the clinical trial results must be publicly available within 12 months from the last visit of the last participant.
  • All study publications must include the registration number/trial ID in the article summary or abstract.

More information can be found here.

 

November 2021: Transparency Scenario in Europe, United States and Canada

An article, Comparing regulatory transparency in Europe, United States and Canada, was published on TranspariMed on November 02, 2021.

This article, provides a comprehensive overview of the key laws and policies governing disclosure of data by major medicine regulators namely European Medicines Agency, the US Food and Drug Administration, and Health Canada. It also compares the data access provided to certain transparency documents by the regulators. This article was originally published by Cambridge university – Transparency of Regulatory Data across the European Medicines Agency, Health Canada, and US Food and Drug Administration

According to the article, the three major medicines regulators are providing more access to key data than ever before. The study focuses on Clinical Study Reports, highly detailed documents that contain important information on the conduct and outcomes of clinical trials that cannot be found elsewhere, but also covers Individual Patient Data plus other types of data and documentation.

The key findings of the article are:

CLINICAL STUDY REPORTS

  • Redactions – The three regulators make only “minimal” redactions to Clinical Study Reports (CSRs) to remove commercially confidential information and data that may endanger patients’ anonymity. Those redactions “generally did not hamper the interpretation of evidence”.
  • Proactive disclosure – Only Health Canada and the European Medicines Agency proactively disclose new CSRs. While the Canadian regulator makes CSRs fully public, the European regulator places restrictions on who can access them, and how. The US Food and Drug Administration has yet to start proactively disclosing CSRs.
  • Reactive disclosure – All three agencies have mechanisms that allow researchers to gain access to older CSRs and other regulatory data upon request. Health Canada provides CSRs far faster and in a more accessible format than the other two regulators do.

INDIVIDUAL PATIENT DATA

Access to Individual Patient Data – Access to IPD via regulators is still impossible in practice. Only the US Food and Drug Administration releases IPD on request, but it when does so, it redacts the data so heavily that they are useless. The European Medicines Agency has formally committed to making IPD accessible in future, but this is not likely to happen any time soon. Health Canada does not have an IPD sharing policy.

ACCESS TO OTHER TYPES OF DATA

The three regulators differ widely in which other types of data they would release.

The article concluded that regulatory data pertinent to public health and clinical medicine, that were used to support the approval of medicines and medical devices are now available proactively or in response to information requests. Over the next decade, regulatory agencies should make Individual patient data available, and additional resources might be needed to ensure the long-term viability of regulatory data sharing programs and to encourage researchers to take advantage of the data that is — for now — more available than ever before.

More information can be found here.

August 2021: Canada Update

On August 23, 2021, Health Canada posted an update on the consultation paper that was released on May 20, 2021. This consultation paper focuses on the key policy proposals to modernize Canada’s clinical trials regulatory framework. One of the points discussed was clinical trial transparency. Along with the consultation paper, an online questionnaire was provided to seek feedback from the interested industry and non-industry stakeholders including all interested Canadians.

Interested stakeholders could refer to the consultation paper and send feedback either via an online questionnaire or by sending a written submission by email. The consultation feedback ran from May 20, 2021, till July 04, 2021.

The feedback received during this consultation will help make a decision with respect to outstanding proposed regulatory policy, and program consideration for each product line in the future.

A summary report on the discussions and comments received named “What we heard” is planned to be published in fall 2021.

May 2021: Canada Update

Health Canada launched a consultation paper on May 20, 2021. This paper outlines the key policy proposals for the modernization of Canada’s clinical trials regulatory framework. One of the points discussed is clinical trial transparency.

Currently, Health Canada’s Clinical Trials Database provides information related to Phase I, II and III clinical trials involving drugs and conducted in patients. Health Canada also encourages the sponsors to register the clinical trials on public registries like ClinicalTrials.gov and ISRCTN. Health Canada is examining options for how to best design and implement measures to promote the registration of Canadian clinical trials in public registries as well as public disclosure of the results (results reporting). These measures may include the development of new policies and regulations while making clinical trial information more accessible to the public with help of information technology such as artificial intelligence (AI).

One approach being considered would be to develop a new policy that would guide sponsors step by step with processes related to registration and results reporting.  Alternatively, the department could begin with new regulatory requirements for registration in the initial phase, with policy measures to address results reporting.

Some of the elements of registration and results reporting under consideration are outlined below:

Registration
Health Canada is exploring policy and regulatory options for the registration of authorized Canadian clinical trials investigating drugs, medical devices and natural health products (NHPs). Canadian trial sponsors may be asked to register their trials in an existing, international registry that has been deemed eligible by the department within a prescribed timeframe. The trial sponsor might also be asked to notify Health Canada with proof of their registration (e.g., registry link and trial identifying number), within a certain timeframe after completing registration.

Public Disclosure of Results
Health Canada is also exploring policy and regulatory options for the requirement of public disclosure or reporting of trial results. This would mean that Canadian trial sponsors would be asked to publicly report trial results, and may be asked to notify Health Canada within prescribed timeframes once the results have been made public.

April 2021: Canada Regulatory Update

As per the Forward Regulatory Plan 2021-2023: Modernization of the Regulation of Clinical Trials, published on April 01, 2021, Health Canada is proposing to amend sections of the Food and Drug Regulations, Natural Health Products Regulations and the Medical Devices Regulations.

This proposal along with aligning the regulatory framework for clinical trials in Canada will also align Canada with global best practices regarding oversight and public access to information on clinical trials.

October 2020: Canada Regulatory Update

Health Canada published a guidance document, Public release of clinical information for drugs and medical devices in COVID-19 interim orders applications on October 07, 2020.

The document explains the process for the public release of safety and efficacy/effectiveness information reviewed under ‘interim order respecting the importation, sale and advertising of drugs for use in relation to COVID-19 (September 16, 2020)‘ and ‘interim order respecting the importation and sale of medical devices for use in relation to COVID-19(March 18, 2020)‘. Information in applications that have been authorized, including those authorized and then revoked, is in scope for public release. Information in applications that are refused and were never authorized is out of scope for public release.

A final redacted and anonymized package is published on Health Canada’s Clinical Information Portal within 120 calendar days from the day an authorization is issued. This process is in accordance with the timelines given in the Public Release of Clinical Information (PRCI) guidance document.

Publication of safety and efficacy information used to support drug interim order applications

  • The first 60 days of the 120-day publication process are allocated for the company to review the clinical information. The company uses the Proposed Redaction Control Sheet (Appendix E, Public Release of Clinical Information (PRCI) guidance document) to propose any redaction of confidential business information (CBI).
  • Within 30 days of receiving the proposal package, Health Canada will complete and return the assessment of the proposed CBI redactions and anonymization methodology for the protection of personal information.
  • The manufacturer will be given 15 days to make the revisions and resubmit.
  • The final assessment will be sent to the manufacturer within 5 days of receiving the revised package.
  • The manufacturer must format and submit the final redacted and anonymized clinical documents within 5 days of receiving the final assessment.
  • The final redacted documents will be published within 5 days of receiving the final sequence.

Publication of safety and effectiveness information used to support medical device interim order applications

  • The CBI and personal information from the interim order application, for which information request is received, will be assessed and redacted by Health Canada.
  • A copy of the release package will be sent for the manufacturer’s review. Any further proposed redactions by the manufacturer must be received within 14 calendar days.
  • Any further redactions proposed by the manufacturer will be assessed.
  • In-scope documents will be published within 120 days following receipt of the request.

April 2020: Comparing Guidances on COVID-19 Disruptions of International Clinical Trials

On April 08, 2020, Ropes & Gray published a document comparing the guidance documents related to COVID-19, its impact on and additional requirements for conducting the clinical trials. The guidance documents involved are issued by the European Medicines Agency (“EMA”), the French National Agency for Medicines and Health Products Safety (“ANSM”), the German Federal Ministry of Health (“BfArM”), the Italian Medicines Agency (“AIFA”), the Spanish Agency for Medicines and Health Products (“AEMPS”)Switzerland’s Swissmedic and swissethics, the Australian Department of Health, the Brazilian Health Regulatory Agency (“ANVISA”)Health Canada, and Singapore Health Sciences Authority (“HSA”).

Earlier, on April 02, 2020, a comparative chart was published summarizing the guidance documents issued by FDA, EMA, MHRA and PMDA.

The comparisons include initiating a new clinical trial, continuing a clinical trial, any changes (amendments) to a clinical trial, informed consent changes, study visits, COVID-19 screening procedures, monitoring
activities, investigational product distribution and study reporting.

March 2019: Canada Update

Health Canada regulation on “public access to clinical information on drugs and medical devices” is published

March 20, 2019: New amendments to the Food and Drug Regulation and the Medical Devices Regulations are published in the Canada Gazette. These amendments regarding the disclosure of clinical trial information will now allow the public release of clinical information on drugs and medical devices.

The information submitted to Health Canada in a drug submission, namely clinical summaries, reports and supporting data of clinical trials submitted in support of a drug submission, was considered as confidential business information (CBI). Now, such information will no longer be treated as confidential following a final regulatory decision and will be released to the public.