CADTH Pharmaceutical Reviews Update — Issue 26

See Pharmaceutical Reviews Update ― Issue 26 for important news and information regarding CADTH’s 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 CADTH 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 CADTH reviews. We hope this will help patient groups determine their returns on investment when contributing, show what information is of most benefit to CADTH 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

   CADTH 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 CADTH website to ensure the insights are available to the broader medical and research community.

CADTH Program Updates

1. Revisions to the Fee Schedule for CADTH Pharmaceutical Reviews
   1.1 New Complex Review Process

   As described in previous versions of the CADTH Procedures for CADTH Reimbursement Reviews, CADTH 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, CADTH 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, CADTH 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

   CADTH has been receiving an increase in applications that contain multiple indications (e.g., different target populations). As stated in the Fee Schedule for CADTH 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 CADTH to review the application.

   In response to inquiries, CADTH has updated the Fee Schedule for CADTH Pharmaceutical Reviews to provide additional clarity regarding the scenarios where multiple fees would be assessed. CADTH 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 CADTH 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 CADTH 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 CADTH Reimbursement Reviews have been revised to specify that sponsors are required to notify CADTH 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 CADTH regarding important changes to the regulatory review timelines.

   Sponsors are required to notify CADTH 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 CADTH 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.

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

   In either of the above scenarios, CADTH may revise the target expert committee meeting date to better align the revised regulatory review timelines.

   3.2 Updating CADTH Regarding the Regulatory Status

   CADTH has recently encountered situations where sponsors are not proactively notifying CADTH 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 CADTH resources to be used in the most efficient manner.

4. Pre-Submission Meetings

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

   4.1 Requirement for Pre-submission Meetings 

   Effective for all pre-submission meetings that are scheduled on or after January 4, 2022, CADTH will require all sponsors to complete and submit a standardized pre-submission briefing document for pending applications to the CADTH reimbursement review. The purpose of the pre-submission briefing paper is to provide CADTH with the information required to adequately prepare for the pre-submission meetings. The information must be provided using the CADTH 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, CADTH will be moving from Zoom to Microsoft Teams to host the pre-submission meetings. In addition, CADTH 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, CADTH will require the sponsor to complete a checklist to confirm that they are complying with the CADTH economic requirements. This new requirement is effective for all applications filed on or after January 4, 2022. CADTH hopes this will improve transparency of what deficiencies CADTH 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

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

   5.3 Legal Disclaimers in Economic Evaluations

   CADTH 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. CADTH 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 CADTH. Any sponsors who have questions regarding the inclusion of a disclaimer should contact CADTH prior to filing the application.

6. Reconsideration Process
   6.1 Reconsideration Template

   CADTH 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

   CADTH has revised section 9.5.6 of the Procedures for CADTH Reimbursement Reviews to expand the potential list of attendees at reconsideration meetings. At the sponsor’s request, CADTH may extend an invitation to INESSS to observe the reconsideration meeting. In these situations, CADTH 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

   CADTH 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

   CADTH 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, CADTH is not issuing provincial funding summaries for oncology drugs. While the current data platform is not able to provide these summaries, CADTH 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

   CADTH 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.