CADTH Pharmaceutical Reviews Update — Issue 28

See Pharmaceutical Reviews Update ― Issue 28 for important news and information regarding the Canada's Drug Agency drug review programs. Highlights from this issue include: 

• a new Sponsor’s Summary of Clinical Evidence template for sponsors 
• clarification regarding the reconsideration process  
• clarification of pharmacoeconomic requirements 
• revised confidentiality guidelines 
• consultations on new pharmaceutical review processes. 

Update for Patients and Communities 

1.  Committee Nominations for Patient Members 
Canada's Drug Agency is currently seeking nominations for new patient members (amongst others) for its expert and advisory committees. Members on expert committees will be asked to voice patients’ perspectives to improve the quality of assessments of medical procedures, devices, and drugs in Canada. Advisory committee members will be asked to provide advice on issues relevant to the Canada's Drug Agency mandate from the perspective of someone using the Canadian health care system. Details about the nomination process, roles, eligibility requirements, and more are available on cadth.ca.  

Applications are open until April 25, 2022.  

Canada's Drug Agency Program Updates 

1. New Application Requirements 

In July 2019, Canada's Drug Agency sought consultation on the inclusion of a systematic literature review as a requirement for applications that are filed for review through the reimbursement review process (see Proposal to Revise Category 1 Requirements for details). Canada's Drug Agency heard from stakeholders that revisions to the reimbursement review process should be phased in gradually, because of the numerous changes that were occurring within the Canadian regulatory and health technology assessment processes at that time. Canada's Drug Agency acknowledged this feedback and decided to focus on aligning the oncology and non-oncology reimbursement review processes before mandating the systematic literature review requirement. However, Canada's Drug Agency communicated that we would be pursuing this procedural revision as it offers efficiencies and will promote alignment with Canadian and international health technology assessment requirements. Due to the increasing volume of applications, Canada's Drug Agency is launching this procedural revision to ensure the sustainability of the reimbursement review process. The new requirements will be effective for all applications targeting the April 2023 expert committee meetings, including:  

• applications received on or after October 17, 2022, for oncology drugs  
• applications received on or after October 31, 2022, for non-oncology drugs.  

The new requirements will apply to all applications reviewed through the standard review and complex review processes. However, a systematic literature review will not be required for applications filed through the tailored review process. 

A summary and links to the new requirements are provided in the following. 

1.1 New Sponsor Summary of Clinical Evidence Template  

The new sponsor summary of clinical evidence template is divided into the 5 sections described as follows. These have been designed based on the format that is typically used by sponsors when filing clinical summaries with Canada's Drug Agency (not currently a requirement, but many sponsors routinely include such documents). The goal is to allow the sponsor an opportunity to concisely summarize the key clinical information for the drug under review in a single document. It is important to note that Canada's Drug Agency will continue to produce a clinical report and the sponsor’s document will not be posted on the Canada's Drug Agency website. 

Section 1: Background Information  
In this section the sponsor is required to summarize key background information regarding the drug under review and the condition for which the drug under review is indicated. Please ensure that statements are appropriately referenced. 

Section 2: Systematic Literature Review 
In this section the sponsor is required to summarize the results of a systemic literature review. The literature review must be conducted and reported in accordance with the instructions provided within this template. 

Section 3: Summary of Extension Studies   
In this section the sponsor is required to summarize long-term extension studies. The sponsor should ensure that all source documentation, including the clinical study report (if available), is included in the application materials. If data from long-term extension studies are not available at the time of filing the application, this should be noted within this section (i.e., do not delete the section if there are no data available).  

Section 4: Summary of Indirect Comparisons  
In this section the sponsor must summarize all indirect comparisons that have been included in the application. In addition to this summary, the sponsor must provide the complete technical reports for the indirect comparisons, as described in the Procedures for Canada's Drug Agency Reimbursement Reviews. Any sponsors who have not included one or more indirect comparisons in the application should explain within the template why an indirect comparison is not relevant for the review and/or why an indirect comparison was not feasible with the available information (i.e., do not delete the section if there are no data available).  

Section 5: Summary of Studies Addressing Important Gaps in Pivotal and Randomized Controlled Trial Evidence   
This section allows the sponsor to summarize evidence from additional studies that address the important gaps in the evidence presented in sections 2 and 3 of the template. Prior to completing section 5, sponsors must clearly identify the gaps in the evidence that has been provided in each of the preceding sections. Examples of gaps in the evidence include:  

• studies designed to demonstrate safety and effectiveness in relevant patient populations that were not included in the clinical trials 
• studies designed to address outcomes that require longer-term follow-up and were not investigated in the clinical trials and/or extension studies 
• studies that address uncertainty regarding the dosage of the drug under review that is used in actual clinical practice. 

Canada's Drug Agency will consider the information provided by the sponsor in section 5 and make a case-by-case determination if the additional evidence will be included in the Canada's Drug Agency clinical report. The inclusion of evidence from section 5 in the Canada's Drug Agency clinical report will be determined solely by Canada's Drug Agency based on the following factors:  

• The additional information may address a clear and relevant gap in the pivotal and randomized controlled trial evidence. 
• The sponsor has provided the additional information in a format that allows Canada's Drug Agency to complete a detailed review and appraisal of the data (e.g., in accordance with CONSORT or STROBE reporting guidelines).  

1.2 Research Information Systems File With References 

Along with the completed summary of clinical evidence template, sponsors will be required to include a Research Information Systems (RIS) file in the application with the references that have been cited in the template. This will allow the sponsor’s references to be easily imported when completing the Canada's Drug Agency reports.  

2. Clarification Regarding Reconsideration Requests 

Canada's Drug Agency has been receiving requests for reconsideration that are focused on the rationale provided by the expert committees for the pricing conditions included in the recommendations (e.g., reasons noting that a particular reduction in price could be required for the drug under review to be considered cost-effective). Canada's Drug Agency will not accept these requests for reconsideration as they are related to the findings of the Canada's Drug Agency economic report as opposed to the committee’s recommendation. The rationale for Canada's Drug Agency not accepting these requests is as follows:  

• As stated in the Procedures for Canada's Drug Agency Reimbursement Reviews, a request for reconsideration can be made only on the grounds that the recommendation is not supported by the evidence that had been submitted or the evidence identified in the Canada's Drug Agency review report(s). A request for reconsideration cannot be made solely because a sponsor or the participating drug programs disagree with the recommendation.  
• When the draft recommendation is issued, sponsors have already been provided with an opportunity to review and comment on the Canada's Drug Agency economic report. The stakeholder feedback period and reconsideration process are not intended to provide additional opportunities for the sponsor to comment on issues that have been or should have been highlighted in the sponsor’s comments on the draft Canada's Drug Agency report(s).   
• The sponsor’s comments on the draft Canada's Drug Agency economic report are provided to the expert committee members in accordance with the Procedures for Canada's Drug Agency Reimbursement Reviews.  

Overall, the refiling of commentary on the Canada's Drug Agency economic report through the request for reconsideration process is not an efficient use of resources; as such, these requests will not be accepted by Canada's Drug Agency.  

3. Clarification of Pharmacoeconomic Application Guidelines 

Canada's Drug Agency has revised the Procedures for Canada's Drug Agency Reimbursement Reviews to clarify that only 1 economic evaluation can be included in an application to Canada's Drug Agency for the review of a single indication. For example, the following will not be accepted by Canada's Drug Agency: 

• including more than one economic model for the review of a single indication 
• submitting both a cost-minimization analysis and cost-utility analysis for the review of a single indication. 

4. Revised Confidentiality Guidelines 

At the request of industry, Canada's Drug Agency has revised the confidentiality guidelines within the Procedures for Canada's Drug Agency Reimbursement Reviews to provide additional clarity on when requests for redaction will and will not be accepted by Canada's Drug Agency. A new summary table has been included to address common sources of information and whether or not the information is considered to be confidential by Canada's Drug Agency. This additional clarification will help sponsors when preparing their requests for redaction and limit the need for extensive dialogue to resolve disagreements between Canada's Drug Agency and the sponsor.   

5. Updated Reimbursement Status of Comparators Template 

At the request of industry, Canada's Drug Agency has revised the Reimbursement Status of Comparators template to better accommodate drugs being reviewed through the interim plasma protein process.  

6. Canada's Drug Agency Consultations on New Pharmaceutical Review Processes 

6.1 Proposal for Non-Sponsored Reimbursement Review  

The current Canada's Drug Agency reimbursement review process requires an eligible sponsor (e.g., pharmaceutical manufacturer or provincially recognized tumour group) to file an application to initiate the review of a drug. The dependence on an external sponsor to file an application can create gaps in the review and reimbursement landscape when eligible sponsors are unable or unwilling to file an application for review by Canada's Drug Agency. In these situations, the public drug programs typically receive requests for reimbursement from the patient and clinical communities; however, they are unable to leverage a reimbursement recommendation from a pan-Canadian process to support their decision-making. This can result in duplication of effort for the public drug programs, inconsistency in access for patients, and the potential failure to realize the clinical and economic benefits of repurposing drugs for use in patient populations where there are unmet medical needs.  

Canada's Drug Agency is seeking stakeholder feedback on a proposal for a new review process that will provide the public drug programs with reimbursement recommendations in selected situations where there is no sponsor to file an application. The Canada's Drug Agency Proposal for Non-Sponsored Reimbursement Reviews document provides a summary of the non-sponsored reimbursement review process for the purposes of stakeholder consultation.  

To provide comments on the proposal, please use the Survey Monkey feedback template. Feedback must be received by 5:00 p.m. EDT on April 14, 2022. If you have any questions about the feedback process, please email Canada's Drug Agency. We thank you in advance for your interest in the Canada's Drug Agency non-sponsored drug reimbursement review process. 

6.2 Proposal for New Streamlined Drug Class Reviews 

Through consultation with public drug programs, Canada's Drug Agency has identified interest in a streamlined approach to optimal use recommendations that would offer an expedited alternative to the current therapeutic review framework. Canada's Drug Agency is seeking stakeholder feedback on a proposal for a more efficient optimal use process that will provide the public drug programs with optimal use recommendations in a timelier manner. A key feature of the proposed process will be the application of existing clinical and pharmacoeconomic data, as opposed to analyses conducted by Canada's Drug Agency. 

The Canada's Drug Agency Proposal for Streamlined Drug Class Reviews document provides a summary of the streamlined optimal use process for the purposes of stakeholder consultation.  

To provide comments on the proposal, please use the Survey Monkey feedback template. Feedback must be received by 5:00 p.m. EDT on April 14, 2022. If you have any questions about the feedback process, please email Canada's Drug Agency. We thank you in advance for your interest in the Canada's Drug Agency streamlined optimal use process.