Scientific Advisory Committee on Health Products for Women (SAC-HPW): Summary of Findings and Advice, October 29 and 30, 2020 Virtual Meeting

Context

The Medical Devices Action Plan (MDAP)^{Footnote 1} was launched in December 2018 to communicate on Health Canada's strategies to strengthen the regulatory framework for medical devices. One of the key commitments in the MDAP is to expand scientific expertise that will help inform regulatory decision-making practices and policies. As part of this commitment, Health Canada has established a new external Scientific Advisory Committee on Health Products for Women (SAC-HPW). The mandate of the SAC-HPW 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 and drugs.

The SAC-HPW is made up of 9 core members with a variety of expertise, knowledge, and perspectives, including patient groups; health professionals such as pharmacists, physicians and nurse practitioners; scientists; academia, and policy.

The inaugural SAC-HPW meeting was May 16-17 2019 and a second teleconference meeting was held on November 28, 2019. This latest meeting was a videoconference meeting on October 29-30, 2020. The objectives of this meeting were to:

1. Provide overview of Health Canada's SGBA+ initiatives and seek feedback on active projects
2. Listen to patient experiences and perspectives with the use of mesh implants
3. Inform and seek feedback on post-market activities and safety review related to mesh implants
4. Seek feedback on the Public Release of Clinical Information (PRCI) Portal and Regulatory Decision Summary (RDS) Database

Overall Summary of Advice

1. To include specific questions to ensure SGBA+ lens is applied in the review process of high-risk devices where clinical data are required to support safety and effectiveness.
2. To consider how to optimally communicate information about devices (potentially the use of social media, the establishment of support groups for women, providing information either about the device or treatment options, and sharing experiences); providing information to international reports and developing an action plan on risk communication strategies to patients and healthcare professionals.
3. To revisit the incident reporting form and related webpages to ensure that the forms are easy to locate, and that the language used is easy to understand, by engaging patient representatives.
4. To expand the range of sources used when retrieving information regarding the complications associated with meshes. This will ensure that more patient experiences are taken into perspective. This can be done, for example, by engaging physicians associations and soliciting feedback from physicians on the concerns patients have regarding the use of mesh products.
5. To analyse feasibility of a registry and/or patient identifier information for tracking of devices and revisit past discussions regarding medical device registries and if need be, engage the right regulatory authorities.
6. To mandate systematic communication from manufacturers of devices to Health Canada to ensure that potential complications and issues are flagged at the pre-market phase.
7. To make the Public Release of Clinical Information and Review Decision Summary databases searchable by sex and gender related terms.
8. Mandatory SGBA+ training for Health Canada staff.

Summary of Discussions

1. Welcome and Opening remarks

Dr. Sharma opened the meeting, re-introduced her role as Chief Medical Advisor for Health Canada and Senior Medical Advisor for the Health Products and Food Branch, and welcomed all SAP-HPW members and Health Canada employees. Dr. Sharma explained that the Department has been contributing significantly to the COVID-19 response being led by the Public Health Agency of Canada in conjunction with the provinces and territories. Despite the unprecedented circumstances, Health Canada's normal operations to authorize and ensure access of health products that are vital to the health and well-being of Canadians have not stopped and continue to remain a top priority. Dr. Sharma emphasized that, although some of the external consultations have been put on hold during the pandemic, the safety and effectiveness of health products for women remains a top priority.

2. Chair's Address, Introduction of Members, Review of Affiliations and Interests (A&I), Review of Agenda

The Chair informed the Committee that the recommendations that have been made by the Committee to date and the resulting actions are being tracked and documented. She emphasized that the role of this Committee is to improve the pre- and post-market regulatory processes and patient experiences. The Chair also informed the members of the open position for an Indigenous representative and encouraged the members to inform Health Canada on any potential candidates. Members provided disclosures of their affiliations and interests. The ad-hoc members provided brief introductions and their affiliations and interests to the Committee.

3. Health Canada Presentation - Actions in Response to SAC-HPW Comments

The Medical Devices Directorate (MDD) Director General (DG) presented the input that was received from industry on how to enable more innovative medical devices to be introduced to the Canadian market. This led to the initiative to modernize the Medical Devices Regulations (MDRs). The aspects of the regulations that would be included in the modernization work are: expanding the terms and conditions; exploring the possibility of leveraging foreign reviews; review of medical device risk classification (specifically the lower risk classes such as Class I and II); strengthening monitoring of medical devices and providing enhanced information to Canadians about the medical devices they use. Health Canada plans to: amend the MDRs by Summer 2022 to allow healthcare professionals to file an Investigational Testing Application (ITA); increase the application of Sex and Gender-Based Analysis (SGBA+), and; consider the implementation of mandatory training of SGBA+ within MDD. Health Canada is a member of the International Medical Device Regulators Forum (IMDRF), which has a main goal of harmonizing the regulations of medical devices internationally. One of the initiatives that Health Canada is developing with the United States Food & Drug Administration (US-FDA) is the single review pilot program to identify the gaps of the MDRs and how to leverage foreign reviews. There may be opportunity to seek the Committee's feedback on pilot projects.

The DG clarified the risk classification system, with Class I (e.g., band-aids, toothbrushes) being the low-risk devices and Class IV being the high-risk devices (e.g., breast implants, pacemakers). Health Canada plans to conduct a review of the low-mid level risk classification (Class I and II) to ensure that requirements for maintaining quality systems are in line with the risk of the products, and to reassess the level of risk posed by these devices. Health Canada is considering implementing a national Unique Device Identifier system in order to better track the devices throughout their lifecycle and therefore, there would be opportunities to leverage real world data and further strengthen the monitoring of devices.

With regards to improving information shared with Canadians, Health Canada has increased the publication of RDS for Class III and IV devices by including the amendment to the licences. Patient-specific labelling is going to be further explored in the risk assessments, which could inform pre-market requirements. Regarding patient involvement, Health Canada has been able to engage various patient groups and has increased patient representation in medical device advisory committees in order to incorporate the advice from patients.

4. Sex and Gender-Based Analysis (SGBA+) Initiatives for Prescription Drugs and Medical Devices

4.1 Overview of Health Canada's SGBA+ Activities for Prescription Drugs and Medical Devices

The Manager of the Office of Paediatrics and Patient Involvement provided an overview of Health Canada's role under the Food & Drugs Act, and elaborated on the integration of SGBA+ across the product lifecycle (from pre- to post-market). The Guidance Document: Considerations for Inclusion of Women in Clinical Trials and Analysis of Sex Differences is the primary tool that is used to encourage manufacturers to include sex variables in their clinical data. It was noted that, although the inclusion of pregnant and breastfeeding women in clinical trials has associated ethical and technical concerns, these subpopulations are put at risk in the post-market space given the insufficient clinical data to demonstrate safety and effectiveness.

Existing SGBA+ learning and training opportunities were presented, including the Sex and Gender Based Symposium, where individuals from government and academia discuss issues and emerging trends in health and gender, and to showcase HC's priority to integrate sex and gender-diverse considerations into the regulatory and scientific work. Expert advice, for example CIHR's Institute of Gender and Health, is sought to help the Department better integrate SGBA+ into the drug and medical device regulatory review processes. The principal investigators of two CIHR-Health Canada research projects presented their respective projects.

4.2 Applying an SGBA+ Lens to Prescription Drug Lifecycle Management: Dr. Lorraine Greaves, Principal Investigator

The principal investigator of this project gave an overview of her project's aim, sex/gender concepts, evidence review, case studies under consideration and next steps. She emphasized that SGBA+ is an ongoing and iterative process that is not just about identifying sex 'differences' to justify action. Gender-related factors are complex to analyze as they are temporal and influenced by psychosocial and cultural determinants. The project objectives are to: (1) review the available evidence on the integration and effects of sex, gender and equity on lifecycle management of prescription drugs, (2) review clinical trial literature for inclusion of sex and gender, (3) examine three illustrative case studies to do a deeper analysis of decision points, and (4) reflect on the available information about Canadian management processes and databases, and offer recommendations for future lifecycle management and SGBA+. The primary sources of evidence are academic literature on lifecycle management of drugs, clinical trials, three case studies (i.e., cardiovascular/hypertension, cancer, and psychotropic drugs), grey literature, public databases and possibly internal data from HC. Impressions of the evidence noted to date are overall lack of sex and gender in research, misuse of sex and gender concepts, and most references referring to "patients" and not women or men.

4.3 Applying an SGBA+ Lens to Medical Device Lifecycle Management: Dr. Anna Gagliardi, Principal Investigator

The project's purpose is to identify how Health Canada can strengthen SGBA+ considerations in the medical device lifecycle by assessing how Health Canada addresses SGBA+ in pre- and post-market activities, and to provide specific recommendations on how to strengthen the consideration of SGBA+ in regulatory processes. The framework and approach is to conduct content analysis of the documents, such as guidance documents, sponsor applications, review criteria/templates, communication to patients and clinicians. Some of the documents will pertain to specific devices for which there have been issues in women (e.g., breast implants, mesh for incontinence/prolapse, birth control).

Committee Deliberations

The Committee can consider the Department's Policy on SGBA+, evaluate whether the Department has been successful at applying the SGBA+ Policy within the drug and medical device regulatory processes, and provide recommendations on how the application of the Policy can be further enhanced. The Committee can conduct reflective practice reviews on both the drug and device regulatory processes, to identify gaps within processes.

A question came up on how to engage with physicians about the products that are problematic and the measures that can be taken to mitigate harm to patients. It was noted that physicians were not aware of the Health Canada webpages such as advisory and recalls and safety alerts notices. There should be an organized monitoring process to allow physicians, industry, and patients to monitor the devices.

It was recommended that, during the investigation process of these projects, the principal investigators capture the positive and negative experiences of patients. Outcomes of studies using real world evidence can be leveraged to identify new ways of conducting post-market surveillance.

The SAC-HPW core members proceeded with an in-camera session.

End of the first day of meeting.

5. Chair's Address, Review of Agenda, Recap Day 1

The Chair expressed appreciation for the ad hoc members' experiences and that it would be good to see some of the committee's responses to those experiences using concrete suggestions. The Chair gave a brief overview of the discussions held during the first day of the meeting. She mentioned that, although the issues discussed were wide ranging, the Committee's intent is to better integrate sex and gender analysis into the management of drugs and devices in Canada so that patient experiences can improve.

The Chair then handed the presentation over to the MDD-DG to introduce the two patient representatives.

6. Patient Experiences/Perspectives on Mesh Implant Products

6.1 First patient representative

The first patient representative mentioned that when she was facing issues with her mesh, she tried to find other forums and groups of women who were experiencing similar issues, which led her to connect with other patients and to start her own patient advocacy group, which grew rapidly. She was looking for solutions in Québec, and met with Health Canada to discuss issues related to meshes and slings. One of her main goals is to help women in filing their incident reports so that Health Canada can have a more accurate representation of the adverse events. This representative has been able to collaborate with the Collège des médecins du Québec in her past endeavours. She has also worked with the Health Authority on the Québec side. She was involved in a report by the Collège des médecins du Québec and highlighted that the 17 recommendations of this report advocated for ceasing the use of meshes in Québec.

The patient representative mentioned that Québec physicians are in denial when health issues related to the use of mesh products are reported. Many of the women who are members of the support group considered filing medical device incident reports to HC, but they were unsure because of their physicians being in denial of the cause. From the research results, it appeared that people do not usually have pain when they first get the slings implanted, and that the pain usually comes over time.

The representative indicated that the Department is not in a position to assess the real risk profile of the device for two reasons: (i) it is impossible to find relevant information regarding meshes on the Health Canada website, unless you have a direct link; and (ii) the terminology used on the website for mesh implants is not consistent with the terminology used in Québec, even using English terminology.

She suggested that Health Canada communicate the fact that Canadians (especially women with slings) can have health problems related to these devices, and that they need to file incident reports to the Department directly. The representative also suggested that Health Canada do more promotion about the incident reporting process for medical devices, such as meshes and slings, so that this can assist with risk assessment. She offered to meet with Health Canada again to share what the issues are with the website and incidents reporting. The incident reporting form has to be simple and more user-friendly.

Over 117 women have traveled to the United States to have their slings removed. Of the 117 women that went to the United States for removal surgery, all events appeared to be as a result of improper installation of the implant by a Canadian physician. It was mentioned that similar to tobacco, many groups have tried advocating for a tax to set up a compensation fund for problematic experiences with drugs and devices. They have also advocated that provinces seek compensation back from the industry.

6.2 Second patient representative

The second patient representative concurred with the first representative that the issues are widespread. The complication rate from transvaginal meshes is far higher than the rate identified in clinical studies. The representative said that the problem is that medical practitioners do not assess the complications as being related to meshes and there is resistance when trying to share these experiences with surgeons. She said that physicians are not recognizing all the complications associated with the use of transvaginal meshes, and are not reporting on any of those complications.

The representative indicated that the use of transvaginal meshes for incontinence has not been explored as extensively as the meshes for prolapse. Many of the litigations around meshes are related to the use of these meshes for the treatment of incontinence and the attention compared to the devices used for prolapse is lacking. Engaging the Canadian Medical Association is necessary because patients feel that the physicians are lacking in current research knowledge or awareness of these issues. A website should be developed for patients and physicians to make it easy for women to report their injuries in case the physicians are not reporting them.

Women should have an information card once they receive the mesh implant, and this card should have all the information regarding that implant. It should also have a link to the Health Canada webpage to report incidents. Health Canada should also have a patient advocate or ombudsman that can help women navigate through the reporting process.

A comment mentioned that meshes and slings are still on the market because they benefit a lot of women and that there are not a lot of alternatives to treat stress urinary incontinence. A follow-up comment indicated that mesh and slings are still on the market because of some of the challenges women face in filing incident reports on the Health Canada website. It was mentioned that issues related to mesh implants appear to not be widely recognized by urologists in Canada, making post-market data for mesh implants inconclusive.

Committee Deliberations summary

Although some women might feel that doctors are not in a position to remove the meshes, it is important to reach out to the surgeons and to ask about their experiences with implanting meshes and their potential complications. Regarding the role of Health Canada, members felt that knowledge translation and conveying the risk information to the physicians is an important factor that further implicates patients when they have to provide their informed consent. A broader perspective is required to better understand this issue. It was clarified that Health Canada has no regulatory authority over physicians and the practice of medicine. It was further indicated that, although it appears that meshes may be dangerous in the hands of those who are not qualified to use them, there may be patients who are benefiting from these meshes especially when implanted by highly skilled surgeons. This is a physician education issue more than a device issue. A question was raised about whether the two patient representatives have been able to reach out to the appropriate regulatory authorities to address the issues they have been experiencing with physicians. One representative has appealed to the Canadian Medical Association. The other representative tried on multiple occasions to reach out to physicians to share her views but she has not been able to get through to them.

It was clarified that Health Canada does make efforts to reach out to women to get feedback on the reporting forms that they fill on its website and that Health Canada does provide assistance to Canadians filing incident reports. Regarding resources that Health Canada could consider, both representatives mentioned the use of social media, the establishment of support groups for women, providing information about the device or treatment, and sharing experiences (which is the starting point for making a collective experience known).

7. Post-market Activities on Mesh Implants

The director gave an overview of the different types of meshes that are available, and that most transvaginal meshes fall under the Class 3 risk assessment. Products in this class are subject to a safety and efficacy review prior to going on the market. Transvaginal meshes are expected to be permanent implants and thus explantation can bring a number of complications. Health Canada has conducted a series of investigations where manufacturers were mandated to submit new information and update their labeling to reflect the risks associated with the products.

Health Canada recently completed a health risk assessment for Single Incision Mini-Slings. The review concluded that more experience of the physician was associated with a better outcome for women. It is important that physicians talk about the risks with their patient.

Health Canada is currently working on the risk assessment for Mid-Urethral Slings. Health Canada is seeking advice from this Committee on how to better amplify our message and how to get information across to people and the intended audience.

In terms of next steps for Single Incision Mini-Slings and Mid-Urethral Slings, Health Canada is looking to conclude the risk assessment early next calendar year, but this all depends on the timing of the feedback received from medical associations and manufacturers.

A question was raised about whether Health Canada had prevalence information regarding these devices and the complications. Health Canada does not currently have that information. There is a lot of different information across the country because these data are provincial and there are privacy considerations in sharing these data. A question was raised about whether it was possible to expand the scope of the source of information Health Canada considers regarding adverse effects, for instance, to include literature from other countries around patient experience as well as other qualitative data. In response, it was explained that Health Canada considers all information that is available, such as grey literature.

Committee Deliberations Summary

A question was raised regarding the webpage on meshes and whether the information on the webpage will include both risks and benefits or just present the risks. In response, it was mentioned that Health Canada's objective is to make the information on the webpage plain language and to communicate all relevant product information.

8. Demonstration of the Public Release of Clinical Information (PRCI) Portal and the Regulatory Decision Summary (RDS) Database

8.1 Public Release of Clinical Information (PRCI) Portal

This portal contains detailed data from clinical trials that are submitted to Health Canada in drug submissions. There are about 2 million pages of data currently available. Any confidential business information and personal information has been removed. This initiative started in 2013 with Vanessa's Law, which permitted the Minister of Health to make public clinical trial information provided to government in drug submissions, for use by external experts and academia for non-commercial purposes. The biggest challenge in publishing clinical study reports is anonymizing them. The information in this database is based on what has been submitted to Health Canada in a drug submission. The only time sex and/or gender information is included is when it was analyzed in the particular trial.

8.2 Regulatory Decision Summary Database

Regulatory Decision Summaries (RDS) and Summary Basis of Decision (SBD) documents are two of the Department's key premarket transparency pieces. The RDS provide an overview of the rationale for the decision made regarding pre-market authorization for each particular product. The SBD provides a rationale for the decision to authorize products for marketing. The difference between them is the level of detail and scope. RDS are published for a wide variety of products, hundreds are published a year, and they are shorter documents. For certain products of higher interest, an SBD is published, which goes into more detail about the rationale for Health Canada's decision to authorize the product. The target audience for both RDS and SBD are patients and healthcare professionals.

Committee Deliberations

It was suggested that this topic be revisited at a future meeting where the Committee can discuss user groups and how to present information that will appeal to these different audiences.

9. Summary of Recommendations from Day 1 and Day 2 and Adjournment of Meeting

The Chair gave a brief summary of the discussions. The Chair mentioned that the table of recommendations and actions is being developed and will be made available to the Committee in due course. The Chair thanked the members for their contributions and closed the meeting.

The SAC-HPW core members proceeded with an in-camera session.

The Record of Proceedings is available upon request. Please submit your request to: hc.policy.bureau.enquiries.sc@canada.ca.