Annual trends for the adverse reaction case reports of health products and medical device problem incidents to Health Canada (2008-2017)

Organization: Health Canada
Type: Report
Published: 2018-10-31

Cat.: H164-247/2018E-PDF
ISBN: 978-0-660-28278-7
Pub.: 180508

Table of contents

• Executive Summary
• Introduction
• Section 1.0 Adverse reaction (AR) case reporting through Canada Vigilance
  • 1.1 Trends in AR reporting (2008-2017)
  • 1.2 Mandatory and voluntary AR case reports
  • 1.3 Seriousness of domestic AR case reports
  • 1.4 Domestic AR cases reported to Health Canada, 2017
    • 1.4.1 Reporters of domestic mandatory and voluntary AR case reports, 2017
    • 1.4.2 Domestic AR case reports by product type, 2017
    • 1.4.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2017
    • 1.4.4 Domestic AR case reports by system organ class, 2017
  • 1.5 Domestic AR cases reported to Health Canada, 2016
    • 1.5.1 Reporters of domestic mandatory and voluntary AR case reports, 2016
    • 1.5.2 Domestic AR case reports by product type, 2016
    • 1.5.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2016
    • 1.5.4 Domestic AR case reports by system organ class, 2016
  • 1.6 Domestic AR cases reported to Health Canada, 2015
    • 1.6.1 Reporters of domestic mandatory and voluntary AR case reports, 2015
    • 1.6.2 Domestic AR case reports by product type, 2015
    • 1.6.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2015
    • 1.6.4 Domestic AR case reports by system organ class, 2015
  • 1.7 Domestic AR cases reported to Health Canada, 2014
    • 1.7.1 Reporters of domestic mandatory and voluntary AR case reports, 2014
    • 1.7.2 Domestic AR case reports by product type, 2014
    • 1.7.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2014
    • 1.7.4 Domestic AR case reports by system organ class, 2014
  • 1.8 Domestic AR cases reported to Health Canada, 2013
    • 1.8.1 Reporters of domestic mandatory and voluntary AR case reports, 2013
    • 1.8.2 Domestic AR case reports by product type, 2013
    • 1.8.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2013
    • 1.8.4 Domestic AR case reports by system organ class, 2013
• Section 2.0: Mandatory problem reports for medical device incidents (MDI) through Canada Vigilance - Medical Devices System (CV-MDS)
• 2.1 Trends in mandatory MDI reports (2008 - 2017)
• 2.2 Seriousness of MDI reports
• 2.3 Mandatory MDI reports, 2017
  • 2.3.1 Class of medical device in mandatory MDI reports, 2017
  • 2.3.2 Mandatory MDI reports by medical specialty of device, 2017
  • 2.3.3 Mandatory MDI reports by device problem category, 2017
• 2.4 Mandatory MDI reports, 2016
  • 2.4.1 Class of medical device in mandatory MDI reports, 2016
  • 2.4.2 Mandatory MDI reports by medical specialty of device
  • 2.4.3 Mandatory MDI reports by device problem category, 2016
• 2.5 Mandatory MDI reports, 2015
  • 2.5.1 Class of medical device in mandatory MDIs, 2015
  • 2.5.2 Mandatory MDI reports by medical specialty, 2015
  • 2.5.3 Mandatory MDI reports by device problem category, 2015
• 2.6 Mandatory MDI reports, 2014
  • 2.6.1 Class of medical device in mandatory MDI reports, 2014
  • 2.6.2 Mandatory MDI reports by medical specialty, 2014
  • 2.6.3 Mandatory MDI reports by device problem category, 2014
• 2.7 Mandatory MDI reports, 2013
  • 2.7.1 Class of medical device in mandatory MDIs, 2013
  • 2.7.2. Mandatory MDI reports by medical specialty, 2013
  • 2.7.3 Mandatory MDI reports by device problem category, 2013
• Section 3.0: Canadian Medical Devices Sentinel Network (CMDSNet) program reporting
• 3.1 Trends in voluntary reports received through CMDSNet (2009 - 2017)
• 3.2 Reports received by CMDSNet (2009 - 2017)
• 3.3 Class of medical devices in CMDSNet reports (2009 - 2017)
• 3.4 Seriousness and patient outcomes of CMDSNet reports (2009 - 2017)
• 3.5 Quality of CMDSNet reports (2009 - 2017)
• 3.6 CMDSNet incident reports by medical specialty (2009 - 2017)
• 3.7 Medical device problem incident categories reported through CMDSNet (2009 - 2017)
• Data limitations
• Glossary

Executive Summary

Health Canada is responsible for protecting the health of Canadians by monitoring and assessing the safety and effectiveness of health products on the Canadian market. Active post-market surveillance of drug adverse events and medical devices incidents is essential to ensure ongoing safety and effectiveness of these health products. Health Canada's primary monitoring mechanisms in this regard are (1) the Canada Vigilance (CV) System for the reporting of adverse drug reactions, (2) the Canada Vigilance - Medical Device Problem Reporting system (CV-MDS) for the reporting of medical device incidents and (3) the Canadian Medical Devices Sentinel Network (CMDSNet) program for the monitoring of medical device incidents in participating hospitals. Manufacturers and importers of prescription health products and medical devices are mandated by regulation to submit adverse event reports to the Health Canada via Canada Vigilance and CV-MDS. Health Canada also receives reports of adverse events, submitted voluntarily, from consumers and health professionals, and in the case of medical device incidents by hospitals participating in the Canadian Medical Devices Sentinel Network (CMDSNet) program. More information can be found on the Adverse Reaction and Medical Devices Incidents Reporting page.

The primary objective of this report is to provide the annual numbers and trends of adverse drug reaction case reports and medical device incident reports to Health Canada between 2008 and 2017. The data are based on reports submitted to Health Canada through Canada Vigilance, the MDS, and CMDSNet.

Multiple factors influence reporting. These include the length of time a drug or medical device is marketed, the market share, size, and sophistication of the sales force, publicity about adverse events and regulatory actions. In some cases, the reported clinical data is incomplete and there is no certainty that the health product caused the reported reaction. As such, quantitative comparisons of health product safety cannot be made from the data and the ability to compare and interpret patterns is limited. However, this report does provide a data snapshot that highlights serious and non-serious reports received for descriptive purposes.

Adverse Reaction (AR) Case Reporting through Canada Vigilance

• More than 64,000 unique domestic AR case reports were submitted to Canada Vigilance in 2017, with 6.5% of those adverse drug events resulting in patient deaths and nearly 20% resulting in patient hospitalisation.
• The total number of domestic AR cases reported to Health Canada has continued to increase annually from 15,551 in 2008 to 64,617 in 2017.
• Voluntary AR case reporting to Health Canada remained fairly consistent at approximately 7,000 cases reported annually during this time period.
• Both serious and non-serious AR case reports have increased over this time period.
• Health professionals consistently submitted the majority of AR case reports.
• Pharmaceuticals and biotechnology products were consistently the product types with the most AR case reports.

Mandatory Problem Reporting of Medical Device Incidents (MDI) through the Medical Devices System (MDS) and CMDS-Net

• More than 11,000 MDI reports were submitted to Health Canada in 2017.
• The total number of reports has continued to increase annually from 4,008 in 2008 to 11,307 in 2017.
• There has been a steady increase in the non-serious (30-day) mandatory MDI reports, while the serious (10-day) mandatory MDI reports have remained fairly constant since 2013 at approximately 2,000 reports per year.
• Health Canada consistently received the most mandatory MDI reports for medical devices in Classes II and III.
• The most common device medical specialty submitted to health Canada through MDI reporting is General Hospital.
• Since its inception in 2009, the number of health authorities reporting to Health Canada through CMDSNet, has increased from 10 to 16.
• Between 2009 and 2017, 1,476 MDI reports have been reported through CMDSNet

All marketed drugs and health products have benefits and risks. Although health products are carefully tested before they are licensed in Canada, some adverse reactions may become evident only after a product is in use by the general population. Tracking suspected adverse reactions through mandatory and voluntary reporting to Health Canada contributes to the ongoing collection of information that occurs once health products are on the market. This information includes: the identification of previously unrecognized rare or serious adverse reactions; domestic and international data regarding benefits, risks and effectiveness of drugs and health products. Health Canada uses the important information submitted on ARs and MDIs to ensure the risk/benefit ratio of health products in Canada remains favourable and available to inform action such as changes in product safety information, or other regulatory actions such as withdrawal of a product from the Canadian market.

Introduction

Adverse reactions are unintended occurrences associated with the use of a health product or a medical device which have caused or could have caused harm to individuals. In the case of health products, an adverse event can also include side effects to the health product. For medical devices, it can be near misses that may have led to serious injury or death if not for timely intervention. Notably, the occurrence of an adverse event does not necessarily mean there is something wrong with the health product or medical device. The event could be the result of incorrect off-label use of the health product, two properly functioning medical devices that were not intended to be used in combination, or to an underlying health or medical condition of the individual.

As mandated by the Food and Drug Regulations, the Natural Health Products Regulations, the Blood Regulations, the Medical Device Regulations and the Safety of Human Cells, Tissues and Organs for Transplantation Regulations, regulated parties are required to submit to Health Canada reports of domestic and foreign adverse reactions including unusual failure in efficacy for new drugs and incident reports on medical devices. Adverse reactions for health products and medical devices cases are also submitted, on a voluntary basis, by health professionals and consumers directly to Health Canada or via regulated parties. In Canada, the Canada Vigilance database contains adverse reaction case reports associated with health products including medication errors and product quality complaints resulting in adverse reactions. Health Canada's Canada Vigilance - Medical Device System (CV-MDS) contains information on problem incidents associated with medical devices ranging from band aids to pace-makers.

The Canadian Medical Devices Sentinel Network (CMDSNet) is an active surveillance program that comprises of acute or community-based healthcare facilities within Canada who report high quality data to Health Canada about adverse events associated with medical devices.

Canada Vigilance, the CV-MDS, and CMDSNet are useful tools for post-market surveillance and are used by Health Canada to monitor potential safety concerns that might be related to a marketed health product or medical device, evaluating a manufacturer's compliance to reporting regulations and responding to outside requests for information. Reported adverse events in these databases are evaluated by scientific reviewers and if a potential safety concern is identified, further evaluation is performed. This may include conducting studies using other large databases, systematic literature reviews, liaising with international regulatory agencies, and checking product monographs and labelling information. Following a comprehensive evaluation, Health Canada may take regulatory action(s) to ensure product safety and protect the public health, including adding warnings, precautions and adverse reaction information to the Product Information and Consumer Medicine Information, restricting the use of the health product or medical device, communicating new safety information to the public, or, in rare cases, removing a health product or medical device from the market. Further information is available on the MedEffect™ Canada Web site. This website also provides access to advisories, recalls, safety reviews and the Health Product InfoWatch publication.

The purpose of this report is to provide a descriptive analysis of the types of adverse reactions, including case reports of health products and medical device incidents, that have been reported to Health Canada between 2008 and 2017. The data are presented in three sections.

• Section 1 includes information on trends of adverse reaction case reports to Health Canada through Canada Vigilance between 2008 and 2017. A more detailed annual breakdown of the data is also presented for the period from 2013 - 2017.
• Section 2 includes trends on medical device incidents reported to Health Canada between 2008 and 2017. A more detailed annual breakdown of the data is presented for the period from 2013 - 2017.
• Section 3 presents data from CMDSNet, Health Canada's active surveillance program on medical device incidents, between its inception in 2009 and 2017.

Section 1.0 Adverse reaction (AR) case reporting through Canada Vigilance

AR cases for the following health products marketed in Canada are reported through Canada Vigilance: prescription and non-prescription medications; natural health products; biologics (includes biotechnology products, vaccines, fractionated blood products, human blood and blood components products, as well as human cells, tissues and organs); radiopharmaceuticals; and disinfectants and sanitizers with disinfectant claims.

AR cases frequently contain multiple reported reactions which are coded in the Canada Vigilance database using the Medical Dictionary for Regulatory Activities (MedDRA). MedDRA uses a hierarchy in order to group similar conditions or reactions together.

1.1 Trends in AR reporting (2008-2017)

Since 2008, there has been a continuous increase in AR case reporting to Health Canada from 15,551 cases in 2008 to 64,617 cases in 2017 (Figure 1).

Figure 1: Number of domestic adverse reaction cases for marketed health products from 2008 to 2017

1.2 Mandatory and voluntary AR case reports

AR cases reports are submitted voluntarily by health professionals and consumers either directly to Health Canada or via regulated parties as mandated by the relevant regulations. Over the years, there has been a significant increase in the number of mandatory AR case reports submitted to Health Canada from 10,124 cases in 2008 to 56,983 cases in 2017. In contrast, the number of voluntary case reports has remained relatively constant (between approximately 5,400 cases and 8,600 cases) during this time period (Figure 2).

Figure 2: Domestic mandatory and voluntary adverse reaction case reporting from 2008 to 2017

1.3 Seriousness of domestic AR case reports

Health Canada receives both serious and non-serious AR case reports for a variety of health products with differing timelines for reporting. For example, as per the Food and Drug Regulations, regulated parties are required to report to Health Canada, serious domestic ARs involving marketed health products and natural health products within 15 days after receiving or becoming aware of the information.

Health Canada defines a serious AR as "a noxious and unintended response to a drug, which occurs at any dose and requires in-patient hospitalization or prolongation of existing hospitalization, causes congenital malformation, results in persistent or significant disability or incapacity, is life-threatening or results in death. Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above, may also be considered serious."

While there has been an increase in both serious and non-serious cases reported to Health Canada, there has been a significantly higher increase in the number of serious cases reported (from 10,717 in 2008 to 44,910 in 2017 for serious cases vs 4,834 in 2008 to 19,707 in 2017 for non-serious cases, Figure 3)

Figure 3: Seriousness of domestic adverse reaction case reports received from 2008 to 2017

1.4 Domestic AR cases reported to Health Canada, 2017

In 2017, Health Canada received 64,617 domestic AR case reports and approximately 500,000 foreign AR case reports. Of the domestic cases, 88% were received via mandatory reporting from regulated parties. Additionally, 70% of the domestic case reports received were identified as serious by the reporter.

1.4.1 Reporters of domestic mandatory and voluntary AR case reports, 2017

The distribution of domestic AR case reporters is shown in Figure 4. These AR case reports were either voluntarily submitted to Health Canada directly by the reporters or the reporters voluntarily submitted the case to a regulated party who are mandated by the relevant regulations to report to Health Canada. At 69%, health professionals, which includes physicians, nurses, and pharmacists, submitted the most AR case reports in 2017.

Figure 4: Domestic adverse reactions case reports by reporter type received for 2017

1.4.2 Domestic AR case reports by product type, 2017

In 2017, Health Canada received domestic AR case reports for four distinct product types: pharmaceuticals, radiopharmaceuticals, biologics, and natural health products. The largest amount of case reports were received for pharmaceuticals (60%) followed by biologics (39%, Figure 5). A further subcategorization of the AR case reports due to biologics is also presented in Figure 5.

Figure 5: Type of suspect products in domestic adverse reaction case reports received by Health Canada in 2017

1.4.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2017

The ATC classification system is a tool for drug utilization research. Table 1 outlines the ten ATC groups most represented by domestically reported suspect products.

1.4.4 Domestic AR case reports by system organ class, 2017

A breakdown, using Medical Dictionary for Regulatory Activities (MedDRA) coding, of the broadest grouping, called the System Organ Class, is shown in Table 2. This System Organ Class includes disorders that affect several body systems or sites (e.g., drug ineffective, fatigue, fever, edema, pain, reactions at the administration site). The most commonly reported AR case reports were general disorders and administration site conditions.

1.5 Domestic AR cases reported to Health Canada, 2016

In 2016, Health Canada received 57,485 domestic AR case reports and approximately 500,000 foreign AR case reports. Of the domestic case reports, 88% were received via mandatory reporting from regulated parties. Additionally, 74% of domestic case reports received were serious in nature.

1.5.1 Reporters of domestic mandatory and voluntary AR case reports, 2016

The distribution of domestic AR case reporters is shown in Figure 6. These AR case reports were either voluntarily submitted to Health Canada directly by the reporters or the reporters voluntarily submitted the case to a regulated party who are mandated by the relevant regulations to report to Health Canada. At 73%, health professionals, which includes physicians, nurses, and pharmacists submitted the most AR case reports in 2016.

Figure 6: Adverse reactions case reports by reporter type for 2016

1.5.2 Domestic AR case reports by product type, 2016

In 2016, the largest amount of AR case reports received by Health Canada were for pharmaceuticals (59%) followed by biologics (40%, Figure 7). A further subcategorization of the AR case reports due to biologics is also presented in Figure 7.

Figure 7: Type of suspect products in domestic adverse reaction case reports received by Health Canada in 2016

1.5.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2016

The ATC classification system is a tool for drug utilization research. Table 3 outlines the ten ATC groups most represented by domestically reported suspect products.

1.5.4 Domestic AR case reports by system organ class, 2016

A breakdown, using Medical Dictionary for Regulatory Activities (MedDRA) coding, of the broadest grouping, called the System Organ Class, is shown in Table 4. The most commonly reported AR case reports were general disorders and administration site conditions.

1.6 Domestic AR cases reported to Health Canada, 2015

In 2015, Health Canada received 49,374 domestic AR case reports and approximately 450,000 foreign AR case reports. Of the domestic case reports, 84% were received via mandatory reporting from regulated parties. Additionally, 74% of domestic case reports received were identified as serious by the reporter.

1.6.1 Reporters of domestic mandatory and voluntary AR case reports, 2015

The distribution of domestic AR case reporters is shown in Figure 8. These AR case reports were either voluntarily submitted to Health Canada directly by the reporters or the reporters voluntarily submitted the case report to a regulated party who are mandated as per the relevant regulations to report to Health Canada. At 73%, health professionals, which includes physicians, nurses, and pharmacists submitted the most AR case reports in 2015.

Figure 8: Domestic adverse reactions case reports by reporter Type for 2015

1.6.2 Domestic AR case reports by product type, 2015

In 2015, the largest amount of AR case reports received by Health Canada were for pharmaceuticals (62%) followed by biologics (36%, Figure 9). A further subcategorization of the AR case reports due to biologics is also presented in Figure 9.

Figure 9: Type of suspect products in domestic adverse reaction case reports received by Health Canada in 2015

1.6.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2015

The ATC classification system is a tool for drug utilization research. Table 5 outlines the ten ATC groups most represented by domestically reported suspect products.

1.6.4 Domestic AR case reports by system organ class, 2015

A breakdown, using Medical Dictionary for Regulatory Activities (MedDRA) coding, of the broadest grouping, called the System Organ Class, is shown in Table 6. The most commonly reported AR case reports were general disorders and administration site conditions.

1.7 Domestic AR cases reported to Health Canada, 2014

In 2014, Health Canada received 44,695 domestic AR case reports and approximately 430,000 foreign AR case reports. Of the domestic case reports, 81% were received via mandatory reporting from regulated parties. Additionally, 75% of domestic case reports received were identified as serious by the reporter.

1.7.1 Reporters of domestic mandatory and voluntary AR case reports, 2014

The distribution of domestic AR case reporters is shown in Figure 10. These AR case reports were either voluntarily submitted to Health Canada directly by the reporters or the reporters voluntarily submitted the case to a regulated party who are mandated by the relevant regulations to report to Health Canada. At 70%, health professionals, which includes physicians, nurses, and pharmacists, submitted the most AR case reports in 2014.

Figure 10: Domestic adverse reactions case reports by reporter type for 2014

1.7.2 Domestic AR case reports by product type, 2014

In 2014, the largest amount of case reports received by Health Canada were for pharmaceuticals (59%) followed by biologics (38%, Figure 11). A further subcategorization of the AR case reports due to biologics is also presented in Figure 11.

Figure 11: Type of suspect products in domestic adverse reaction case reports received by Health Canada in 2014

1.7.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2014

The ATC classification system is a tool for drug utilization research. Table 7 outlines the ten ATC groups most represented by domestically reported suspect products.

1.7.4 Domestic AR case reports by system organ class, 2014

A breakdown, using Medical Dictionary for Regulatory Activities (MedDRA) coding, of the broadest grouping, called the System Organ Class, is shown in Table 8. The most commonly reported AR case reports were general disorders and administration site conditions.

1.8 Domestic AR cases reported to Health Canada, 2013

In 2013, Health Canada received 41,872 domestic AR case reports and approximately 400,000 foreign AR case reports. Of the domestic case reports, 82% were received via mandatory reporting from regulated parties. Additionally, 78% of domestic case reports received were identified as serious by the reporter.

1.8.1 Reporters of domestic mandatory and voluntary AR case reports, 2013

The distribution of domestic AR case reporters is shown in Figure 12. These AR case reports were either voluntarily submitted to Health Canada directly by the reporters or the reporters voluntarily submitted the case to a regulated party who are mandated by the relevant regulations to report to Health Canada. At 67%, health professionals, which includes physicians, nurses, and pharmacists, submitted the most AR case reports in 2013.

Figure 12: Domestic adverse reactions case reports by reporter type for 2013

1.8.2 Domestic AR case reports by product type, 2013

In 2013, the largest amount of case reports received by Health Canada were for pharmaceuticals (60%) followed by biologics (37%, Figure 13). A further subcategorization of the AR case reports due to biologics is also presented in Figure 13.

Figure 13: Type of Suspect Products in Domestic Adverse Reaction Case Reports Received by Health Canada in 2013

1.8.3 Anatomical therapeutic chemical (ATC) system groups from domestic AR case reports, 2013

The ATC classification system is a tool for drug utilization research. Table 9 outlines the ten ATC groups most represented by domestically reported suspect products.

1.8.4 Domestic AR case reports by system organ class, 2013

A breakdown, using Medical Dictionary for Regulatory Activities (MedDRA) coding, of the broadest grouping, called the System Organ Class, is shown in Table 10. The most commonly reported ARs were general disorders and administration site conditions.

Section 2.0: Mandatory problem reports for medical device incidents (MDI) through Canada Vigilance - Medical Devices System (CV-MDS)

For medical devices, a mandatory problem report for an incident is required by the manufacturer and importer concerning any incident that comes to their attention occurring inside or outside Canada and involving a medical device that is sold in Canada. Domestic mandatory reports include incidents of a failure of the device or a deterioration in its effectiveness, or any inadequacy in its labelling or in its directions for use, and/or if the incident has led to the death of or a serious deterioration in the state of health of a patient, user or other person, or could do so if it were to recur.

Medical device problem reports on incidents frequently contain multiple reported problems with a device. These problems are coded into the Medical Device System (MDS) database by Health Canada according to a structured coding system. Recent work by the International Medical Device Regulators Forum (IMDRF) has proposed a three level hierarchical terminology for Medical Device Problem terms/codes. The first level divides problems into 27 broad categories. Health Canada has conducted an exercise to map the codes used in the MDS to these 27 categories.

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Health Canada, maintains a database of all licensed Class II, III, and IV medical devices offered for sale in Canada. This Medical Devices Active Licence Listing (MDALL) database is made searchable and available online for query. Class I medical devices do not require a medical device licence and are monitored by Health Canada through Establishment Licensing.

2.1 Trends in mandatory MDI reports (2008 - 2017)

Since 2008, there has been an increase in mandatory MDI reporting to Health Canada, both from domestic and foreign sources, as demonstrated in Figure 14  below. For the past 10 years, the number of MDIs reported continues its upward trend as Health Canada received 14% more domestic incidents per year on average; domestic incidents have increased from 4,008 in 2008 to 11,307 in 2017.

Figure 14: Number of reported domestic and foreign medical device incidents from 2008 to 2017

Mandatory problem reports for foreign incidents are only required when the incident meets the same conditions as for a domestic incident, but in addition the incident must have resulted in either the manufacturer’s intent to undertake a corrective action or the foreign regulatory body requiring that the manufacturer undertakes a corrective action. As this is a more restrictive set of criteria, the number of foreign mandatory reports is much lower than the number of domestic reports.

2.2 Seriousness of MDI reports

The reporting window after awareness of an incident varies depending on the nature of the incident. A manufacturer or importer must submit a preliminary report within 10 days of awareness of an incident if the incident has led to the death or a serious deterioration in the state of health of a person; whereas, the reporting time frame is 30 days for cases where the incident has not led to the death or a serious deterioration in the state of health of a person, but could do so were it to recur. 10-day reports are more serious, and are prioritised for assessment.

Figure 15 illustrates the distribution of incident seriousness as measured by reporting timeline since 2008. Overall, there has been a slight increase in the serious (10-day) reporting from 587 in 2008 to 1,721 in 2017. While the trend in non-serious (30-day) reporting has increased since 2008, there seems to have been a moderate decline in these reports since 2015.

Figure 15: Reported domestic medical device incidents by seriousness from 2006 to 2017

2.3 Mandatory MDI reports, 2017

In 2017, Health Canada received 11,307 mandatory domestic MDI reports and 858 mandatory foreign MDI reports. The 10-day incident reports accounted for 15% of all domestic incidents received in 2017.

2.3.1 Class of medical device in mandatory MDI reports, 2017

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 16 presents the proportion of reports representing each of the four classes of medical device received in 2017.

Figure 16: Domestic mandatory MDI reports received in 2017 by medical device risk class

2.3.2 Mandatory MDI reports by medical specialty of device, 2017

MDI reports are received for medical devices with a number of different medical specialties. Table 11 outlines the number of reported MDIs for the 10 most common medical specialities in 2017.

2.3.3 Mandatory MDI reports by device problem category, 2017

MDI reports frequently contain multiple problems with a device. Table 12 is a list of the top 10 problem codes recorded in 2017, mapped to the International Medical Device Regulators Forum (IMDRF) Annex A Level 1 codes/terms.

2.4 Mandatory MDI reports, 2016

In 2016, Health Canada received 11,707 mandatory domestic MDI reports and 431 mandatory foreign MDI reports. The 10-day incident reports accounted for 13% of all domestic incidents received in 2016.

2.4.1 Class of medical device in mandatory MDI reports, 2016

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 17 presents the proportion of reports representing each of the four classes of medical device received in 2016.

Figure 17: Domestic mandatory MDIs received in 2016 by medical device risk class

2.4.2 Mandatory MDI reports by medical specialty of device

MDI reports are received for medical devices with a number of different medical specialties. Table 13 outlines the number of reported MDIs for the 10 most common medical specialities in 2016.

2.4.3 Mandatory MDI reports by device problem category, 2016

MDI reports frequently contain multiple reported problems with a device. Table 14 is a list of the top 10 problem codes recorded in 2016, mapped to the International Medical Device Regulators Forum (IMDRF) Annex A Level 1 codes/terms.

2.5 Mandatory MDI reports, 2015

In 2015, Health Canada received 14,101 mandatory domestic MDIs and 399 mandatory foreign MDIs. The 10-day incident reports accounted for 11% of all domestic incidents received in 2015.

2.5.1 Class of medical device in mandatory MDIs, 2015

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 18 presents the proportion of reports representing each of the four classes of medical device received in 2015.

Figure 18: Domestic mandatory MDIs received in 2015 by medical device risk class

2.5.2 Mandatory MDI reports by medical specialty, 2015

MDI reports are received for medical devices with a number of different medical specialties. Table 15 outlines the number of reported MDIs for the 10 most common medical specialities in 2015.

2.5.3 Mandatory MDI reports by device problem category, 2015

MDI reports frequently contain multiple reported problems with a device. Table 16 is a list of the top 10 problem codes recorded in 2015, mapped to the International Medical Device Regulators Forum (IMDRF) Annex A Level 1 codes/terms.

2.6 Mandatory MDI reports, 2014

In 2014, Health Canada received 13,279 mandatory domestic MDIs and 482 mandatory foreign MDIs. The 10-day incident reports accounted for 20% of all domestic incidents received in 2014.

2.6.1 Class of medical device in mandatory MDI reports, 2014

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 19 presents the proportion of reports representing each of the four classes of medical device received in 2014.

Figure 19: Mandatory domestic MDI reports received in 2014 by medical device risk class

2.6.2 Mandatory MDI reports by medical specialty, 2014

MDI reports are received for medical devices with a number of different medical specialties. Table 17 outlines the number of reported MDIs for the 10 most common medical specialities in 2014.

2.6.3 Mandatory MDI reports by device problem category, 2014

MDI reports frequently contain multiple reported problems with a device. Table 18 is a list of the top 10 problem codes recorded in 2014, mapped to the International Medical Device Regulators Forum (IMDRF) Annex A Level 1 codes/terms.

2.7 Mandatory MDI reports, 2013

In 2013, Health Canada received 10,305 mandatory domestic MDIs and 366 mandatory foreign MDIs. The 10-day reports accounted for 16% of all domestic incidents received in 2013.

2.7.1 Class of medical device in mandatory MDIs, 2013

Medical devices are categorised based on the risk associated with their use, with Class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 20 presents the proportion of reports representing each of the four classes of medical device received in 2013.

Figure 20: Mandatory domestic MDI reports received in 2013 by medical device risk class

2.7.2. Mandatory MDI reports by medical specialty, 2013

MDI reports are received for medical devices with a number of different medical specialties. Table 19 outlines the number of reported MDIs for the 10 most common medical specialities in 2013.

2.7.3. Mandatory MDI reports by device problem category, 2013

MDI reports frequently contain multiple reported problems with a device. Table 20 is a list of the top 10 problem codes recorded in 2013, mapped to the International Medical Device Regulators Forum (IMDRF) Annex A Level 1 codes/terms.

Section 3.0: Canadian Medical Devices Sentinel Network (CMDSNet) program reporting

The Canadian Medical Devices Sentinel Network (CMDSNet) is an active surveillance program that relies on a group of dedicated and trained representatives from acute or community-based healthcare facilities within Canada to provide high quality data reports about adverse events associated with all types of medical devices. Only participating institutions can report via this program, and there is no cost to the organization other than their time to submit the reports to Health Canada. These detailed reports obtained from reporting institutions help to better characterize how organizations use certain devices, how problems are perceived and reported, and what may have contributed to a particular event.

By creating this two-way communication between Health Canada and the clinical community to better understand the environment, it is possible to identify practical risk mitigation strategies, such as increasing awareness of hazards and conditions of use, improving the labelling, and improving safety standards. The overall goals for the CMDSNet program are to contribute to better quality risk assessments and earlier regulatory interventions and to provide health professionals and citizens with timely information to make informed health choices which will help maintain and improve the health of Canadians.

3.1 Trends in voluntary reports received through CMDSNet (2009 - 2017)

Since the start of the CMDSNet project in 2009, Health Canada has seen an increase in the number of voluntary reports received. The subset of the CMDSNet reports within the overall voluntary reports received is demonstrated in the calendar year statistics shown in Figure 21. In 2016, a new site enrolled with automated reports coming directly to CMDSNet, which accounts for this steep increase in overall reports.

Figure 21: Number of reports received by CMDSNet from 2009 to 2017

3.2 Reports received by CMDSNet (2009 - 2017)

The number of reporting health care organizations has risen from the original 10 in the pilot to 16 in 2017. The initial intent was to ensure that all the provinces and territories were represented. We continue to look for CMDSNet hospitals in Nunavut and the Yukon. These health organizations vary in size from one hospital to a whole provincial health authority that represents over 100 sites and 9,000 inpatient beds. The locations representing CMDSNet participating sites in 2017 are shown in Figure 22.

Figure 22: Location of CMDSNet sites in 2017

3.3 Class of medical devices in CMDSNet reports (2009 - 2017)

Medical devices are categorised based on the risk associated with their use, with class I devices representing the lowest potential risk (e.g., mercury thermometers) and Class IV devices presenting the greatest potential risk (e.g., certain pacemakers/defibrillators). Prior to selling a device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Figure 23 presents the proportion of reports representing each of the four classes of medical device received via CMDSNet since 2009. There are many class II and III’s used in a hospital setting so this may account for many reports.

Figure 23: Proportion of reports representing each of the four classes of medical devices

3.4 Seriousness and patient outcomes of CMDSNet reports (2009 - 2017)

Health Canada considers all pertinent information provided to assess the health hazard of a device and assigns a priority to the reported incident. The program has three levels of priority for medical devices incidents: priority I, priority II and priority III.

Figure 24 and Figure 25 illustrates the distribution of report seriousness and patient outcomes received via CMDSNet since 2009. As seen in Figure 24, the Priority I reports make up 11% of the reports received; however, only 4% of CMDSNet reports have actually led to serious injury/death as shown in Figure 25. Many reports for class II devices are of a quality nature so these are typically less serious. The potential-for-harm reports are interesting because an injury has not yet occurred so there is an opportunity to improve them prior to an incident occurring that would involve harm to patients.

Figure 24: Distribution of seriousness received by CMDSNet from 2009 to 2017

Figure 25: Distribution of patient outcomes received by CMDSNet from 2009 to 2017

3.5 Quality of CMDSNet reports (2009 - 2017)

Health Canada grades the CMDSNet reports using a modified scale developed by the World Health Organisation (WHO). The modified WHO scale is used to rate the reports on a scale of 1-5 using pre-set rating criteria, with 5 being the best quality and 1 being un-enterable; 88% were of the highest quality as assessed by the modified WHO scale (Figure 26).

Figure 26: Quality of reports as graded by a modified WHO scale from 2009 to 2017

3.6 CMDSNet incident reports by medical specialty (2009 - 2017)

Table 21 shows the Top 5 medical specialties of devices submitted to Health Canada via CMDSNet from 2009 to 2017. The majority (88.3%) are reports in the general hospital, surgical, cardiovascular, gastroenterology and urology, and anaesthesiology Areas. This data seems to correspond to where the most procedures are happening in the hospitals.

3.7 Medical device problem incident categories reported through CMDSNet (2009 - 2017)

CMDSNet reports frequently contain multiple reported problems with a device. These problems are coded into the Medical Device System (MDS) database using the device codes from the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Only the device-specific codes from MedDRA are used for CMDSNet reports. Since 2009, nearly 70% of the incidents received are categorized as device defect or malfunction as seen in Table 22. Misuse of devices comprises only 1% of the reports.

Data limitations

Interpretation of Suspected Adverse Reaction Data needs to take into account certain limitations about the data, such as:

1. AR cases are suspected associations which reflect the opinion or observation of the individual reporter. The data does not reflect any Health Canada assessment of association between the health product and the reaction(s).
2. Often, it is not possible to determine if an AR reported to Health Canada is a result of using a specific health product. Other factors contributing to the reaction could be a person's health conditions or other health products they are using at the same time.
3. Several factors may influence the number of cases received such as length of time a product is on the market, extent of use, media coverage, regulatory actions, and method of data collection (cases submitted voluntarily versus organized data-collection systems). For example, ARs to health products may be reported more frequently in organized data-collection systems (e.g., patient registries, surveys, and patient support and disease management programs) which may affect the pattern of reporting. As such, it is not possible to compare the risk between health products based solely on the numbers of cases.

The following considerations should be taken into account when interpreting information pertaining to medical device problem incidents reports:

1. Reportable incidents involving a medical device that affected one or more patients, users or other persons, on the same, or different, dates, are reported to Health Canada as separate incidents, because each incident was a separate event.
2. Reportable incidents involving the failure of more than one medical device, of the same or different lot number, that affected the same patient or user are to be reported to Health Canada as separate incidents.
3. Counts of reports will differ from counts of incidents, as for a given incident we can receive multiple reports from multiple reporters. This can also result in duplicate incidents, if the duplicate reports are not identified.

Glossary

Definitions for a number of terms used in this document are set out in the glossary below.

Accident

In the context of the Safety of Human Cells, Tissues and Organs for Transplantation Regulations, an accident means an unexpected event that is not attributable to a deviation from the standard operating procedures or applicable laws and that could adversely affect the safety of a transplant recipient or the safety, efficacy or quality of cells, tissues or organs.

Adverse reaction

An adverse reaction means a noxious and unintended response to a marketed health product.

Cells

In the context of the Safety of Human Cells, Tissues and Organs for Transplantation Regulations, a cell means the fundamental biological unit of a human organism that is for use in transplantation.

Case report

In the context of adverse reactions to health products, a case report consists of all information describing the adverse reaction(s) experienced by one patient at one time and suspected of being related to the use of one or more health products/medical devices; thus, an adverse reaction case report will include an initial adverse reaction report as well as any subsequent additional information received as follow-up report(s).

Domestic adverse reaction

An adverse reaction occurring in Canada.

Drug

According to the Food and Drugs Act, a drug includes any substance or mixture of substances manufactured, sold or represented for use in:

1. the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animals;
2. restoring, correcting or modifying organic functions in human beings or animals; or
3. disinfection in premises in which food is manufactured, prepared or kept.

Error

In the context of the Safety of Human Cells, Tissues and Organs for Transplantation Regulations, an error means a deviation from the standard operating procedures or applicable laws that could adversely affect the safety of a transplant recipient or the safety, efficacy or quality of cells, tissues or organs.

Foreign adverse reaction

An adverse reaction occurring outside Canada to a product with the same combination of active ingredients that is marketed in Canada irrespective of variations in the formulation, dosage form, strength, route of administration, or indication.

Health product

Health Product includes products regulated under the Food and Drugs Regulations ("drugs") and the Natural Health Products Regulations ("natural health products"). Drugs include both prescription and non-prescription pharmaceuticals; biotechnology products and biologically-derived products such as vaccines, serums, and blood derived products; disinfectants; and radiopharmaceuticals.

Importer

A person, other than the manufacturer of a device, who causes the medical device to be brought into Canada for sale.

Incident

In the context of mandatory problem reporting for medical device incidents, information on the incident refers to the circumstances required to be reported under Section 59 of the Medical Device Regulations.

Malfunction or deterioration

A failure of a device to perform in accordance with its intended purpose when used in accordance with the manufacturer's instructions. Malfunction is synonymous with "fault".

Manufacturer

In the context of medical device incidents, as is defined in section 1 of the Medical Device Regulations, this term means a person who sells a medical device under their own name, or under a trade mark, design, trade name or other name or mark owned or controlled by the person, and who is responsible for designing, manufacturing, assembling, processing, labeling, packaging, refurbishing or modifying the device, or for assigning it to a purpose, whether those tasks are performed by that person or on their behalf.

Market authorization holder (MAH)

In the context of health products, an MAH means the entity that holds the Notice of Compliance, the Drug Identification Number (DIN), the Natural Product Number (NPN), the Homeopathic Medicine Number (DIN-HM), or the product license.

MedEffect™ Canada

MedEffect™ Canada has been developed by Health Canada's Marketed Health Products Directorate:

• to provide centralized access to relevant and reliable health product safety information as it becomes available, in an easy to find, easy to remember location. This includes access to Health Canada's advisories and recalls; the Health Product InfoWatch; and the Canada Vigilance Adverse Reaction Online Database;
• to make it as simple and efficient as possible for health professionals and consumers to complete and file adverse reaction reports via Web, phone, fax or mail; and
• to build awareness about the importance of reporting adverse reactions to Health Canada, and how this information is used to identify and communicate potential risks.

Medical device incident priority I:

A situation in which there is a reasonable probability that the use of, or exposure to, a device has led to the death or serious deterioration of the state of health of a patient, user or other person, or a reasonable belief that recurring exposure could lead to the death or serious deterioration of the state of health of a patient, user or other person.

Medical device incident priority II:

A situation in which the use of, or exposure to, a device may cause temporary deterioration of the state of health of a patient, user or other person, or where the probability of serious deterioration of health is remote.

Medical device incident priority III:

A situation in which the use of, or exposure to, a device is not likely to cause any deterioration of the state of health, of a patient, user or other person.

Natural health product (NHP)

A substance set out in Schedule 1 of the Natural Health Products Regulations or a combination of substances in which all the medicinal ingredients are substances set out in Schedule 1 of the Natural Health Products Regulations, a homeopathic medicine or a traditional medicine, that is manufactured, sold or represented for use in:

1. the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state or its symptoms in humans;
2. restoring or correcting organic functions in humans; or
3. modifying organic functions in humans, such as modifying those functions in a manner that maintains or promotes health.

However, a natural health product does not include a substance set out in Schedule 2 of the Natural Health Products Regulations, any combination of substances that includes a substance set out in Schedule 2 of the Natural Health Products Regulations or a homeopathic medicine or a traditional medicine that is or includes a substance set out in Schedule 2 of the Natural Health Products Regulations.

Physician

A physician means a person who is entitled to practice the profession of medicine under the laws of the province in which the person provides medical service

Product monograph (PM)

A product monograph is a factual, scientific document on the drug product that, devoid of promotional material, describes the properties, claims, indications, and conditions of use for the drug, and that contains any other information that may be required for optimal, safe, and effective use of the drug.

Regulated parties

For the purposes of this document, a regulated party refers to the party who is mandated by either the the Food and Drug Regulations, the Natural Health Products Regulations, the Blood Regulations, the Medical Device Regulations and/or the Safety of Human Cells, Tissues and Organs for Transplantation Regulations to abide by the requirements of the respective regulations.

For example, Market Authorization Holders are required by the Food and Drug Regulations to report adverse reactions involving marketed health products to Health Canada; Blood establishments are required by the Blood Regulations to report adverse reactions involving human blood and blood components for transfusion to Health Canada.

Serious adverse reaction

A serious adverse reaction is a noxious and unintended response to a marketed health product that occurs at any dose and that requires in-patient hospitalization or a prolongation of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability or incapacity, that is life threatening or that results in death.