CADTH Pharmaceutical Reviews Update — Issue 26

See Pharmaceutical Reviews Update ― Issue 26 for important news and information regarding the Canada's Drug Agency drug review programs. Highlights from this issue include:

• Revised application fee schedule
• Revised procedures for pre-submission meetings
• Revised economic requirements
• Health Canada pause the clock process
• Minor update to expert committee schedule

Update for Patients and Communities

1. Impact of Patient Involvement 

   We recognize the effort that goes into providing patient perspectives to Canada's Drug Agency reviews of medical procedures, devices, and drugs. In the past we had provided a thank you letter to each patient group who contributed input. Instead, we are now going to publicly thank the patient groups who contribute each month as well as highlight how patient insights are used. Every few months, we’ll share updated examples of how insights from patients and caregivers are used in Canada's Drug Agency reviews. We hope this will help patient groups determine their returns on investment when contributing, show what information is of most benefit to Canada's Drug Agency teams and committees, and inspire new patients and communities to get involved. See Impact of Patient Involvement to read examples from the summer.

2. Patient and Caregiver Panel Meeting On Dementia

   Canada's Drug Agency plans to host a patient and caregiver panel meeting on the topic of dementia in early December. We will be bringing together a small, but diverse, group of those living with dementia to discuss important treatment goals and supports. Insights from the panel may be used in upcoming reviews of medical procedures, devices, diagnostics, and drugs related to Alzheimer disease and dementia. A report summarizing the meeting will be posted on the Canada's Drug Agency website to ensure the insights are available to the broader medical and research community.

Canada's Drug Agency Program Updates

1. Revisions to the Fee Schedule for Canada's Drug Agency Pharmaceutical Reviews
   1.1 New Complex Review Process

   As described in previous versions of the Canada's Drug Agency Procedures for Canada's Drug Agency Reimbursement Reviews, Canada's Drug Agency defined higher complexity reviews as follows:

   • Drugs reviewed through the cell and gene therapy review processes
   • Standard reviews for drugs with characteristics such as being a new first-in-class therapeutic option, drugs reviewed through one of Health Canada’s expedited review pathways (i.e., priority review or advance consideration under Notice of Compliance With Conditions [NOC/c] policy), and drugs that have an undefined place in therapy.

   For both the above noted review types, Canada's Drug Agency would implement process enhancements such as greater consultation with clinical experts (including the formation of pan-Canadian advisory panels of clinical specialists), greater consideration of non-randomized evidence (included real-world evidence) that could address important gaps in the evidence from pivotal/phase III studies, and a review of potential ethical issues during the committee deliberations.

   Following an internal review, Canada's Drug Agency will be implementing the following changes effective for all applications that are received on or after January 4, 2022:

   • Introducing a new ‘Complex Review’ process that replaces the existing cell and gene therapy review process and the standard review process for higher complexity reviews.
   • Applying a Schedule E application fee for drugs reviewed through the complex review process.

Revised Application Types and Fee Schedule Effective January 4, 2022

2. Submissions Requiring Multiple Application Fees

   Canada's Drug Agency has been receiving an increase in applications that contain multiple indications (e.g., different target populations). As stated in the Fee Schedule for Canada's Drug Agency Pharmaceutical Reviews, a case-by-case assessment is made regarding the application fee when there are multiple indications included in one application. Multiple fees are assessed to ensure that the application fee accurately reflects the level of effort and resources required by Canada's Drug Agency to review the application.

   In response to inquiries, Canada's Drug Agency has updated the Fee Schedule for Canada's Drug Agency Pharmaceutical Reviews to provide additional clarity regarding the scenarios where multiple fees would be assessed. Canada's Drug Agency bases this decision on the following four factors:

   • The indications are sufficiently different to require consultation with different clinical specialists.
   • The indications are best addressed through separate review reports and/or expert committee recommendations.
   • The indications have been studied in separate clinical development programs (e.g., separate clinical trials for each population).
   • The sponsor has filed different economic analyses and budget impact analyses for each of the indications.

   The final decision is made by Canada's Drug Agency based on the considerations noted above. It is important to note that not all the factors need to be met in order for an application to warrant multiple application fees.

   Any sponsor’s that are uncertain about the application fees are encouraged to contact Canada's Drug Agency early in the pre-submission phase to seek guidance ([email protected]).

3. Regulatory Status Updates
   3.1 Pausing the Clock during Health Canada Review

   The Procedures for Canada's Drug Agency Reimbursement Reviews have been revised to specify that sponsors are required to notify Canada's Drug Agency if the pause the clock mechanism has been implemented during the regulatory review process. This change is being implemented to provide greater consistency with how and when sponsors are notifying Canada's Drug Agency regarding important changes to the regulatory review timelines.

   Sponsors are required to notify Canada's Drug Agency once the pause the clock request has been accepted by Health Canada. At that time sponsors are required to provide the following information:

   • The specific issues being addressed by the sponsor while the clock is paused (please note that details are not required and should not be provided to Canada's Drug Agency for any issues related to the quality review by Health Canada [e.g., chemistry, manufacturing, and controls]).
   • The revised target timelines for the regulatory review process.

   Canada's Drug Agency will review the issues being discussed between the sponsor and Health Canada and determine the following:

   • If the issues are not anticipated to have a significant impact on the Canada's Drug Agency review (e.g., not anticipated to affect the indication or dosing information), Canada's Drug Agency may elect to continue with the review in accordance with the existing timelines.
   • If Canada's Drug Agency believes the issues may have an impact on the Canada's Drug Agency review, the review may be temporarily suspended pending clarification of the outstanding information.

   In either of the above scenarios, Canada's Drug Agency may revise the target expert committee meeting date to better align the revised regulatory review timelines.

   3.2 Updating Canada's Drug Agency Regarding the Regulatory Status

   Canada's Drug Agency has recently encountered situations where sponsors are not proactively notifying Canada's Drug Agency regarding important changes to the indication and/or dosing information during the review of pre-NOC submissions. All sponsors are reminded that clear and rapid communication regarding the regulatory status is the best way to avoid delays in the review process and allow Canada's Drug Agency resources to be used in the most efficient manner.

4. Pre-Submission Meetings

   Canada's Drug Agency has revised section 4.1 of the Procedures for Canada's Drug Agency Reimbursement Reviews to provide more details regarding the pre-submission meeting process, introduce a new requirement for reporting key information and questions to Canada's Drug Agency, and revised target timelines for providing the slides to Canada's Drug Agency.

   4.1 Requirement for Pre-submission Meetings 

   Effective for all pre-submission meetings that are scheduled on or after January 4, 2022, Canada's Drug Agency will require all sponsors to complete and submit a standardized pre-submission briefing document for pending applications to the Canada's Drug Agency reimbursement review. The purpose of the pre-submission briefing paper is to provide Canada's Drug Agency with the information required to adequately prepare for the pre-submission meetings. The information must be provided using the Canada's Drug Agency template and must be filed no later than 10 business days before the scheduled date of the pre-submission meeting. Failure to provide the form within this time frame may result in postponement of the meeting.

   4.2 Meeting Platform and Slides for Pre-submission Meetings

   Effective for all pre-submission meetings that are scheduled on or after January 4, 2022, Canada's Drug Agency will be moving from Zoom to Microsoft Teams to host the pre-submission meetings. In addition, Canada's Drug Agency staff will no longer advance slides on behalf of the sponsor during the meeting; sponsors must assign one or more of their presenters to advance the slides.

5. Economic Requirements 
   5.1 New Requirement: Completed Checklist of Economic Requirements

   To address the number of deficiencies observed recently, Canada's Drug Agency will require the sponsor to complete a checklist to confirm that they are complying with the Canada's Drug Agency economic requirements. This new requirement is effective for all applications filed on or after January 4, 2022. Canada's Drug Agency hopes this will improve transparency of what deficiencies Canada's Drug Agency may identify at the screening process and thus allow the sponsor to identify these issues before submitting thus avoiding potential delays.

   5.2 Clarification of Economic Requirements

   Canada's Drug Agency has added clarification in the Procedures for Canada's Drug Agency Reimbursement Reviews regarding pricing and dosing information, considerations for the analyses to be provided, and supporting information. Canada's Drug Agency has also clarified the perspectives to consider in the budget impact analysis.

   5.3 Legal Disclaimers in Economic Evaluations

   Canada's Drug Agency has received several economic models where access to the model requires the user to review and agree to terms and conditions and/or acknowledge a legal disclaimer added by the vendor or sponsor. Canada's Drug Agency has also incorporated a new clause with regards to disclaimers and legal notices in sponsor’s models. These models will not be accepted for review by Canada's Drug Agency. Any sponsors who have questions regarding the inclusion of a disclaimer should contact Canada's Drug Agency prior to filing the application.

6. Reconsideration Process
   6.1 Reconsideration Template

   Canada's Drug Agency has updated the reconsideration template to assist sponsors in preparing their requests for reconsideration. Specifically, we recommend that sponsors use clear and descriptive subheadings within the template that highlight each of the issues being raised by the sponsor. Under each subheading, sponsors should clearly articulate the evidence and key information that supports their perspective regarding the issue(s) of interest. This approach ensures that each of the issues identified by the sponsor are clearly delineated within the documentation that is considered by the expert committee.

   6.2 Reconsideration Meetings

   Canada's Drug Agency has revised section 9.5.6 of the Procedures for Canada's Drug Agency Reimbursement Reviews to expand the potential list of attendees at reconsideration meetings. At the sponsor’s request, Canada's Drug Agency may extend an invitation to INESSS to observe the reconsideration meeting. In these situations, Canada's Drug Agency will extend the invitation to INESSS; however, their participation is optional. Section 1 of the reconsideration request template has been updated to allow sponsors to communicate whether they would like INESSS to be invited to the meeting.

7. Provisional Funding Algorithm Process
   7.1 Revised Input and Feedback Templates

   Canada's Drug Agency has conducted an initial review of the stakeholder input and feedback that has been provided in the provisional funding algorithm process. As a result, the stakeholder input and feedback templates have been updated to provide additional guidance and help focus stakeholder contributions on the issues that are being reviewed and discussed by the expert panel.

   7.2 New Tool Summarizing the Algorithm Process

   Canada's Drug Agency has prepared a new poster that provide stakeholders with an overview of the provisional funding algorithm process.

8. Provincial Funding Summaries for Oncology Drugs

   At this time, Canada's Drug Agency is not issuing provincial funding summaries for oncology drugs. While the current data platform is not able to provide these summaries, Canada's Drug Agency is continuing to look for other opportunities. Stakeholders will be notified if and when these reports will be generated again in the future. Any stakeholders with questions regarding the reimbursement status of oncology drugs should consult resources within the individual jurisdictions.

9. Expert Committees
   9.1 Minor Revision to Expert Committee Schedule

   Canada's Drug Agency has posted a revised version of the expert committee meeting schedule to correct a minor error in the date ranges for submissions targeting the May 2022 and June 2022 meetings for non-oncology drugs. The ranges for the submission received dates have been revised by 1 business day as follows:

   • The end date for the range targeting the May 2022 meeting has been revised from January 7, 2022 to January 6, 2022.
   • The beginning of the range for those targeting the June 2022 meeting has been revised from January 10, 2022 to January 7, 2022.