Scientific Advisory Committee on Health Products for Women (SAC-HPW): Summary of findings and advice, June 23^rd, 2021 virtual meeting

Context

The Scientific Advisory Committee on Health Products for Women (SAC-HPW)'s mandate is to provide Health Canada with timely patient-centered, scientific, technical, medical and clinical advice on current and emerging issues regarding women's health and the regulation of medical devices as well as drugs. The Committee will examine issues across the health product life cycle, from development to real-world use, with a focus on patient perspectives and experiences.

The SAC-HPW is made up of 9 core members with a variety of expertise, knowledge, and perspectives, including: patient representatives; health professionals; academics with scientific and policy expertise.

The objectives of the videoconference committee meeting that occurred on June 23rd, 2021 were to:

1. Revisit the Health Canada drug approval process
2. Provide an overview of recent data packages and how subgroup analyses, including sex, inform labelling, and gather feedback on how to improve the communication of such information through labelling
3. Gather early, high-level feedback on a Branch Sex- and Gender-Based Analysis (SGBA) Plus strategy under development.

Summary of discussions

1. Welcome and opening remarks

The Chief Medical Advisor opened the meeting by acknowledging the traditional and unceded territory of the Algonquin Anishnaabeg People, on which the meeting was hosted. She provided updates on Health Canada's recent activities in response to the COVID-19 pandemic since the previous meeting and on the departmental Sex and Gender-based Analyses Plus Action Plan. She also provided an overview of the Health Products and Food Branch (HPFB) mandate and scope as a reminder to help focus the committee's discussions.

2. Chair's address, introduction of members, review of Affiliations and Interests (A&I), review of agenda

The Chair reminded the committee of its mandate and scope and encouraged members to focus their recommendations accordingly. The issues under consideration during this meeting included: an overview of how HPFB integrates SGBA Plus considerations in its evaluation of data packages to authorize (or deny) drugs on the Canadian market; and the draft SGBA Plus Action Plan for the Branch.

3. Health Canada presentation – Actions in response to SAC-HPW comments and past recommendations

The Medical Devices Directorate provided an update on Health Canada's activities in response to previous recommendations put forward by the committee. Committee members requested a few clarifications to increase their understanding of why some recommendations could not be enacted.

4. Session #1a: The drug authorization process

The Therapeutic Products Directorate (TPD)'s provided an overview of the drug authorization process. The presenter outlined Health Canada's role as regulator and HPFB's mandate regarding the approval of drugs, and outlined the requirements (i.e. evidence of sufficient quality, safety, and efficacy) that must be demonstrated for the product to be granted market authorization. Committee members discussed and clarified data requirements underlying the drug authorization process.

5. Session #1b: Considerations for SGBA Plus during drug submission review & labelling

The Biologics and Radiopharmaceutical Drugs Directorate presented on how various factors such as sex, age, and ethnicity are currently incorporated in drug development. The presenter also spoke to the various guidance documents, both Canadian and international, that mandate the drug industry to take these factors into account. The committee was informed that pharmaceutical companies were required to conduct subgroup analyses (i.e., analyze data disaggregated by the factors of interest depending on the drug, the population, and other relevant considerations) prior to conducting confirmatory Phase III clinical trials. The goal of this requirement is for studies to maintain methodological/statistical integrity, even if statistical power is not reached for each subgroup of interest. Health Canada uses subgroups mainly to examine the consistency of an effect between different groups, in support of the overall interpretation of the study. The presenter explained how conclusions were shared through product labelling. Through the overview of a few recent submissions, the presenter showed that women generally account for ~40% of clinical trial samples, although this representation varied by disease and indication. Diseases that are known to affect more women than men were associated with a higher proportion of women in the associated clinical trials. The Therapeutic Products Directorate presented additional evidence to support the proportional representation of women in clinical trials. The committee discussed the challenges and opportunities associated with subgroup analyses during the regulatory approval process.

6. Session #2: SGBA Plus Action Plan for the Health Products and Food Branch (in development)

The Biologics and Radiopharmaceutical Drugs Directorate presented the draft HPFB SGBA Plus Action Plan. The presenter provided an overview of existing documents and guidance documents that are used to support SGBA Plus in the various directorates of the Branch as well as the various activities underway to build SGBA Plus capacity. The presenter explained the challenges to implementing SGBA Plus in the Branch and proposed actions for overcoming these challenges over the short-, medium- and long-term. She solicited committee members' feedback on the suggested approaches.

7. Secretariat remarks

The Chair of the Secretariat provided updates to members regarding the upcoming October meeting, ongoing process improvements, and membership renewal.

8. Summary of recommendations and adjournment of meeting

The Chair noted that a new core member is still being sought and that efforts to this end would continue over summer. She thanked members for their participation and the meeting was adjourned.

Overall summary of advice

1. Investigate opportunities to ensure sponsors apply sex and gender based analysis to clinical trials and discuss how any related issues were addressed at each stage of drug development when meeting with the Therapeutic Drugs Directorate or Biologics and Radiopharmaceutical Drugs Directorate, including at the pre-submission meeting. Explore levers (incentives, deterrents) for adherence to Canada's SGBA Plus policy by sponsors. Initiate leadership internationally in this regard.
2. Establish consistency in addressing SGBA Plus throughout the lifecycle management process of drugs.
3. Require that product information about pre-specified subgroups (e.g., sex subgroups) be provided in a systematic way in the Product Monograph, including if there is insufficient data to comment.
4. Ensure that there is a sufficient sample size of relevant subgroups in clinical trials.
5. Review design of early phase clinical trials to assess sex-related factors and intersections with age, ethnicity, and race.
6. Encourage sponsors to conduct meta-analyses to support their subgroup analyses.
7. Request mandatory reporting of sex composition of trial populations, and request single-sex trials whenever possible to determine sex differences or sex-related factors.
8. Conduct post-market studies on sex and gender to complement or enhance pre-market clinical trials.
9. Drug development program must address sex-related issues such as dose adjustment and clearance. Phases I and II need to investigate and conduct subgroup analyses and sex-related factors in mixed and single-sex trials.
10. Consider adding a capacity-building stream into the Health Products and Food Branch (HPFB) SGBA Plus Action Plan to include activities such as training within HPFB.
11. Move the HPFB SGBA Plus Action Plan away from a strictly sex difference paradigm to analysing sex- and gender-related factors.
12. Revise the medium- and long-term goals of the HPFB SGBA Plus Action Plan to ensure they are feasible within the chosen timeframe.
13. Determine which elements of the HPFB SGBA Plus Action Plan are mandatory, to facilitate the prioritization of action items. Likewise, consider changes to internal templates and processes (e.g., SOPs) to facilitate the implementation of actions.
14. In the HPFB SGBA Plus Action Plan, add goals regarding harmonization and cooperation between HPFB and other international regulators (United States Food and Drug Administration, European Medicines Agency, etc.) to ensure continued alignment of Canadian practices with international standards, when applicable.
15. Align the HPFB SGBA Plus Action Plan with the overarching federal SGBA Plus audit and action plan accountabilities, including the recent SGBA Plus audit on Health Canada and associated Management Response Action Plan.
16. Bring the HPFB SGBA Plus Action Plan back to each SAC-HPW meeting to discuss the status of the implementation of the plan.

The Record of Proceedings is available upon request, as long as no confidential information is discussed. Please submit your request to: policy.bureau.enquiries@hc-sc.gc.ca