The following update was posted on ClinicalTrials.gov What’s New Section, on November 10, 2020:
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.
During the COVID-19 pandemic, EMA is implementing exceptional measures to maximise the transparency of its regulatory activities on treatments and vaccines for COVID-19 that are approved or are under evaluation.
EMA is achieving this by shortening its standard publishing timeframes and publishing information it does not normally publish for other medicines.
Under this practice, the clinical trial data for COVID-19 medicines will be published on clinical data website after marketing authorisation. As a standard practice, such publication is suspended until further notice for other medicines.
Introducing a New Online Platform for African Trials
The African Academy of Sciences (AAS) in June 2020, launched a first iteration of the Clinical Trials Community (CTC) online platform with features that will increase the visibility of African clinical trial sites and investigators with potential to participate in COVID-19 clinical trials. This platform will promote & enhance intra-Africa collaboration around clinical trials with hopes of reducing duplication of work across the region & accelerating the fight of combatting COVID-19.
The main goal of the CTC platform will be to:
- Increase the visibility of African Clinical Trialists and Sites by indicating the geographical location and corresponding disease burden
- Reduce unnecessary duplication of efforts by providing access to current site feasibility data
- Improving predictability by providing access to regulatory and ethics requirements across countries and an online platform for sponsor engagement
- Reducing bias in funding across countries and disease areas by highlighting gaps and promoting synergy across strategic funders
Therefore, the CTC online platform seeks to strengthen all the aspects of clinical trials and translational sciences capacity in the continent.
The full CTC platform is due for launch in late 2020 and will cover all diseases of public health importance for the African continent.
The FDA on May 11th updated its final guidance on “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” to address new questions, including the use of alternate laboratory or imaging centers, video conferencing and postmarketing requirements. The update also features clarifications to questions addressed in previous versions of the guidance on managing protocol deviations and amendments and on steps sponsors should take when considering administering investigational products at home instead of at clinical trial sites.
The European Commission and European Medicines Agency (EMA) on April 28th updated their Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Pandemic adding advice on distribution, data verification and communicating with authorities. The updated EMA guidance follows an April 16th similar update from the FDA, which added seven new questions and answers to its document. The update marks the third version of the guidance from the Commission, EMA and the Heads of Medicines Agencies and provides new recommendations on the distribution of investigational medicinal products (IMPs) and data verification under social distancing measures and resource limitations.
The guidance also clarifies how clinical trial sponsors should communicate urgent issues to regulatory authorities. “The aim is to mitigate the disruption of clinical research in Europe and therefore the negative effects of the pandemic, without compromising on quality and safety,” the Commission said in April 28th press release, noting that the guidance will be revoked once the crisis in Europe has passed.
Jim Kremidas, Executive Director of the Association of Clinical Research Professional (ACRP) posted a PhRMA blog post on April 29, 2020, titled “Preserving Clinical Research Sites During the Coronavirus Pandemic”. The blog post cites the April 8th press release of a study conducted by Continuum Clinical in partnership with ACRP which found 31% of clinical research study sites fear total closure, as COVID-19-related stay-at-home orders and patient concerns over interacting with health care professionals continue to increase. Nearly 80% of sites indicated at least one of their current clinical trials had been put on hold or cancelled in recent weeks.
Of the sites who reported patient dropouts:
- 80% said patients are unwilling to visit the site for study appointments
- 52% indicated they believe patients fear interacting with any medical professionals who may be in contact with COVID-19 patients
- Only 19% of sites said they thought patients would permit home nursing visits by clinical trial staff, a method recently offered by the FDA as an acceptable substitute for scheduled drug administration study visits
The survey also shows investigator sites are facing serious staffing issues, with 38% reporting employees experiencing difficulties working from home and 33% reporting employees are not fully engaged due to coronavirus-related disruptions.
Kremidas states: “Sponsors need to understand how this pandemic is curtailing clinical trial activity and putting many sites on the very edge of financial existence…Sponsors and others have leveraged some of the best aspects of decentralized clinical trials, remote based monitoring, and real-world evidence. In the future this period may be referred to as the “Covid-Catalyst” due to the impact it’s having on advancing clinical operations. As an industry, we are rising to meet a huge challenge with nimble thinking and powerful resolve”.
Following updates were posted on ClinicalTrials.gov on April 28, 2020:
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.
On March 27th the FDA released a Q&A document in an appendix (page 10) to the March 18th “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic” that discusses general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice and minimizing risks to trial integrity during the COVID-19 pandemic. The appendix responds to questions the agency has received.
A protocol amendment is not needed to pause enrollment in a trial to decrease potential exposure to COVID-19, because such a pause would not be expected to significantly affect subject safety, the trial’s scope or its scientific quality, the FDA explains in the Q&A appendix. Sponsors may consolidate several protocol modifications into a single protocol amendment because the agency “recognizes that during the rapidly evolving circumstances of a pandemic, a sequence of changes may be needed to address those circumstances.”
Such consolidation should be done expeditiously, the FDA said. In addition, clinical investigators still must document as protocol deviations any modifications to protocol-specified procedures that occur prior to institutional review board approval and FDA submission of the amendment implementing the changes.
Sponsors can document protocol deviations using their standard processes or, given the larger expected number of deviations, through alternative documentation approaches, the FDA said. “For example, if visits are to be conducted by telephone/video contact rather than at the investigational site as specified in the protocol, documentation that provides a listing of all study visits (e.g., listing study reference number, patient ID, date of visit) that are deviations from the protocol due to the current COVID-19 situation generally would be acceptable,” the document states.
The document also includes advice for sponsors on initiating virtual clinical trial visits and what to do when on-site monitoring is delayed.