Regulations Amending the Food and Drug Regulations (Serious Adverse Drug Reaction Reporting — Hospitals): SOR/2019-190

Canada Gazette, Part II, Volume 153, Number 13

Registration
SOR/2019-190 June 10, 2019

FOOD AND DRUGS ACT

P.C. 2019-746 June 9, 2019

Whereas, pursuant to subsection 30(1.3) footnote a of the Food and Drugs Act footnote b, the Minister of Health has taken into account existing information management systems, with a view to not recommending the making of regulations that would impose unnecessary administrative burdens;

Therefore, Her Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to section 30 footnote c of the Food and Drugs Act footnote b, makes the annexed Regulations Amending the Food and Drug Regulations (Serious Adverse Drug Reaction Reporting — Hospitals).

Regulations Amending the Food and Drug Regulations (Serious Adverse Drug Reaction Reporting — Hospitals)

Amendments

1 The heading before section C.01.017 of the Food and Drug Regulations footnote 1 is replaced by the following:

Serious Adverse Drug Reaction Reporting — Manufacturers

2 The Regulations are amended by adding the following after section C.01.020:

Provision of Information Under Section 21.8 of Act

C.01.020.1 (1) For the purposes of section 21.8 of the Act, hospitals are the prescribed health care institutions that shall provide information that is in their control to the Minister about a serious adverse drug reaction.

(2) The following prescribed information about a serious adverse drug reaction that is in a hospital’s control shall be provided to the Minister in writing within 30 days after the day on which the serious adverse drug reaction is first documented within the hospital:

(3) A hospital is exempt from section 21.8 of the Act in respect of the reporting of information referred to in subsection (2) if

(4) In this section, hospital means a facility

3 Section C.10.004 of the Regulations is repealed.

Coming into Force

4 These Regulations come into force on December 16, 2019, but if they are registered after that day, they come into force on the day on which they are registered.

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the regulations.)

Executive summary

Issues: Real-world effects of a therapeutic product continue to be uncovered once a product is authorized and in use by the broader population. People can react differently to the same therapeutic product, due to genetic variations, the environment, lifestyle factors, age, and the presence of more than one disease or illness. Sometimes, these adverse reactions or incidents are serious enough that they can be life-threatening, leading to hospitalization and, in some instances, death.

Rapid advances in science, medicine and the way information is communicated provide opportunities for real-world data to be collected and assessed by Health Canada as part of a life-cycle approach to the regulation of therapeutic products. Reports of serious adverse drug reactions (SADRs) and medical device incidents (MDIs) by manufacturers and importers (collectively referred to as “industry” for the purposes of this document, where appropriate), health care professionals and the public are often the first sign of emerging safety problems.

Currently, only industry is required to report SADRs and/or MDIs; reporting by health care professionals and consumers is voluntary. Health Canada is aware that, at present, a potentially significant number of SADRs and MDIs go unreported.

Description: The regulations will amend the Food and Drug Regulations and the Medical Devices Regulations to require hospitals to report SADR- and MDI-related information directly to Health Canada. The collection and assessment of this real-world information will help Health Canada to better monitor the safety of therapeutic products once they are on the Canadian market.

Cost-benefit statement: The incremental costs for hospitals are estimated at $514,629,670 (present value). It is also expected to cost Health Canada $8,502,091 (present value) to process and assess the reports. As a result, the total anticipated costs associated with the regulatory reporting requirements translate to a present value cost of $523,131,761 over a 10-year period, discounted at 7%. These costs are expected to be offset by a number of qualitative benefits, including greater confidence in the safety of marketed therapeutic products on the Canadian market, anticipated changes in health care professionals’ prescribing behaviour, better information for patients, and potentially avoided health care costs and lost productivity.

“One-for-One” Rule and small business lens: The “One-for-One” Rule and small business lens do not apply, as there are no impacts on businesses.

Background

Like all global therapeutic product regulators, Health Canada recognizes that there are limitations to the understanding of the potential benefits and risks of harm of a product prior to its authorization for sale. While authorizations for sale are based on the outcomes of clinical trials, important knowledge is gained throughout each stage of a product’s life- cycle, including once it is on the market.

In November 2014, the Protecting Canadians from Unsafe Drugs Act (Vanessa’s Law) [Vanessa’s Law] received royal assent. Vanessa’s Law provides Health Canada with the legislative tools necessary to regulate the authorization for sale and safety of therapeutic products footnote 2 based on a life-cycle approach (i.e. products are rigorously and appropriately assessed for quality, benefits, harms and uncertainties both before and after they enter the general market). This approach is being adopted by regulatory agencies worldwide, and is based on the recognition that important information about the safety and effectiveness of a drug can be learned after a product is brought to market and is in use by the broader population.

Health Canada’s monitoring of therapeutic products plays a vital role in public health and patient safety, providing health care professionals and patients with up-to-date knowledge about the products they use to treat their health. The product monograph (for drugs) and instructions for use (for medical devices) are the basis of information for health care professionals on how to use a therapeutic product safely and effectively. As more knowledge and experience is gained, product labelling, including the product monograph and instructions for use, may be modified and improved. This post-market safety knowledge is built from several data sources, including adverse drug reaction (ADR) and MDI reports. By reporting ADRs and MDIs, patients and health care professionals are participating in the system that helps make therapeutic products safer.

Health Canada is continuously looking for ways to strengthen the post-market knowledge base to enhance the safety and reduce the uncertainty associated with the real-world benefits and harms of therapeutic products. Vanessa’s Law amended the Food and Drugs Act (the Act) to introduce, among other things, a new requirement in section 21.8 of the Act for prescribed health care institutions to provide the Minister of Health with prescribed information that is in their control about an SADR or MDI that involves a therapeutic product.

Regulatory amendments are necessary to prescribe the types of health care institutions that will be required to report, the types of reportable SADRs and MDIs, the types of reportable therapeutic products, the information required to be included in a report, and the timelines for reporting.

Issues

Canada has one of the safest and most rigorous drug and medical device authorization systems in the world. While clinical trials are an important part of the pre-market assessment of therapeutic products, real-world effects continue to be uncovered once a product is authorized and in use by the broader population. People can react differently to the same therapeutic product, due to genetic variations, the environment, lifestyle factors, age and the presence of more than one disease or illness. Sometimes these effects can be life-threatening, lead to hospitalization and, in rare instances, death.

Rapid advances in science, medicine and the way information is communicated now provide opportunities for real-world data to be collected and assessed as part of a life-cycle approach to the regulation of therapeutic products. Reports of SADRs and MDIs by industry, health care professionals and the public are important for managing the risks associated with the use of these therapeutic products, and are often the first sign of emerging safety problems. Hospitals are uniquely positioned to identify and report SADRs and MDIs, thereby broadening the real-world data available to Health Canada.

At present, reporting in Canada generally consists of two components: reporting by industry on a mandatory basis (a regulatory requirement); and reporting by health care professionals, patients, consumers and health care institutions on a voluntary basis. This voluntary reporting is provided to either the relevant manufacturer or directly to Health Canada. Although it is mandatory for industry to in turn report to Health Canada, they ultimately rely on the information submitted to them on a voluntary basis by health care professionals, patients, consumers, and health care institutions. International studies estimate rates of reporting (to industry or regulatory agencies) to be as low as 1–10%, and there is no evidence to suggest that Canadian reporting rates are higher. footnote 3 This under-reporting of important therapeutic product information is a concern to Health Canada, as it reduces the Department’s ability to identify, at an early stage, potential safety problems and to take action to prevent harm to patients.

Objectives

The central objective of the regulations is to improve the quality and increase the quantity of SADR and MDI reports, and to expand on the real-world evidence used by Health Canada to monitor the safety and effectiveness of therapeutic products, as part of a life-cycle approach to the regulation of such products.

Description

Section 21.8 of the Act introduced the requirement that: “A prescribed health care institution shall provide the Minister, within the prescribed time and in the prescribed manner, with prescribed information that is in its control about a SADR that involves a therapeutic product or a MDI that involves a therapeutic product.”

The regulations will amend the Food and Drug Regulations (FDR) and the Medical Devices Regulations (MDR) to require the reporting, by hospitals, of SADRs and MDIs associated with the use of pharmaceuticals (prescription and non-prescription), biologic drugs (excluding a vaccine administered under a routine immunization program of a province or territory), radiopharmaceuticals, disinfectants and medical devices, within 30 days of first being documented by a hospital.

The regulations define a hospital as a facility that (a) is licensed, approved or designated as a hospital by a province or territory, in accordance with the laws of the province or territory, to provide care or treatment to persons suffering from any form of disease or illness; or (b) that is operated by the Government of Canada and that provides health services to persons who are in-patients. For greater clarity, the proposal also creates a definition for an MDI within the MDR.

The regulations set out the type of information required to be reported to Health Canada. For SADRs, the information is

For MDIs the information is

Hospitals are exempt from reporting SADRs of MDIs under certain circumstances.

For SADR reports, a hospital would be exempt from sending the report to Health Canada if the hospital does not have, in its control, all the information in the list below:

For MDI reports, a hospital would be exempt from sending the report to Health Canada if the hospital does not have, in its control, all the information in the list below:

The reason for exempting the hospital from having to report SADRs and MDIs if it does not have the key pieces of information above is that these pieces of information are necessary for Health Canada to conduct a basic assessment of these reports.

To avoid duplication of reporting schemes that are already in place, hospitals are also exempt from reporting if a SADR only involves one of the following products:

For MDIs, hospitals are exempt from reporting if the MDI involves only a medical device that is the subject of an authorization issued under subsection 72(1) or 83(1) of the MDR. However, reporting is not exempt for SADRs in which multiple products are involved, even though one or several of the implicated products may be on the list of exclusions above.

Where additional information is known within the 30-day time frame, the regulations require that this additional information also be reported to Health Canada. Such information could include the date of the first reaction or incident, any underlying health conditions directly related to the reaction or incident, and patient health outcomes.

To enhance clarity and alignment across the FDR, consequential amendments to Part C, Division 10, of the Regulations (Access to Drugs in Exceptional Circumstances) will be implemented to indicate that prescribed health care institutions are “hospitals” within the same meaning as described above. The term “hospitals” will replace the scope of institutions currently required to report under Division 10 (i.e. all health care institutions authorized by the laws of a province to provide acute care services). To further enhance alignment, the SADR reporting requirements will also replace those currently found in Division 10 (C.10.004).

Regulatory and non-regulatory options considered

Health Canada assessed a range of regulatory and non-regulatory options to collect additional information on SADRs and MDIs, with a view to establishing an approach to reporting by health care institutions that will enable the capture of meaningful, high-quality information and achieve the safety monitoring objectives of Vanessa’s Law, while taking steps not to impose unnecessary burden on health care institutions.

Option 1: Status quo

Currently, only industry is required to report SADRs and MDIs to Health Canada. Since 1965, Health Canada has operated a voluntary reporting system for health care institutions, health care professionals, and consumers. In an effort to encourage and facilitate reporting of ADRs and MDIs by health care professionals, Health Canada has previously undertaken a number of activities, including increasing access to more user-friendly reporting methods, developing educational modules and raising awareness about the importance of voluntarily reporting ADRs and MDIs. Despite these non-regulatory initiatives, reporting rates have remained low. Therefore, the status quo option does not represent a viable means of achieving the objective of Vanessa’s Law to improve the quality and increase the quantity of ADR and MDI reports, thereby ensuring there is sufficient information to detect safety problems.

Option 2: Amending the Food and Drug Regulations and the Medical Devices Regulations — Selected option

With the new authorities introduced by Vanessa’s Law, Health Canada has the ability to take regulatory action in concert with non-regulatory measures to enhance SADR and MDI reporting. This option will amend the relevant regulations to require hospitals to report to Health Canada SADRs and MDIs within 30 days of them first being documented. This is the Department’s preferred option, as it provides a legal mechanism to ensure that events deemed clinically significant by frontline health care professionals working in hospitals are reported to Health Canada with optimal information, thereby broadening the evidence base used to identify new safety signals or confirm existing safety signals generated from other data sources.

In developing the regulatory proposal, options around the following factors were considered.

Applicable health care institutions

The regulations will apply to all hospitals regulated through provincial or territorial legislation, as well as to those operated by the federal government and that provide health services to persons who are in-patients. It is Health Canada’s view that such institutions are most likely to treat patients presenting with SADRs and MDIs. These institutions are well positioned to make and report these observations, and are more likely to have the infrastructure needed to effectively support quality reporting while minimizing the relative burden of such reporting.

Health Canada’s initial proposal was to limit the scope of the reporting requirement to only those hospitals that provided acute care services. Consideration was also given to restricting reporting to a subset of targeted hospitals (e.g. teaching or large community hospitals). However, broadening the scope to all hospitals will likely capture reporting from potentially important facilities, such as chronic care and extended care hospitals and certain mental health facilities, where treatment of such reactions/incidents may occur.

Health Canada also considered expanding the scope of the reporting requirements to include all health care institutions, including those that provide in-patient and out-patient care, diagnostic or therapeutic services, laboratory services, nursing care, etc. While this option in theory could capture the broadest amount of information, there are several reasons why such an approach was found to be less viable. In a real-world setting, patients presenting an SADR or MDI that is observed at any given health care institution would likely be transferred to a hospital for treatment, where reporting of the reaction/incident would then occur. Based on this approach, Health Canada is of the view that the overall number of reports would be sufficient to help identify and validate potential safety issues.

At the time of developing the proposal, Health Canada’s view was that health care institutions outside hospitals were also less likely to have the infrastructure needed to investigate and effectively report SADRs/MDIs, and would likely bear a significant burden to comply with the reporting requirements.

Types of reportable reactions and incidents

The regulations will require hospitals to report all documented SADRs as well as all documented MDIs, including MDIs with the potential to cause harm if they reoccur, where the required information is within the control of the hospital.

The FDR, Part C, Division 1, subsection C.01.001(1.1) define, for the purposes of the Act, an SADR as having the same meaning as in subsection C.01.001(1):

Similarly, the MDR, paragraphs 59(1)(a) and (b), state that an MDI

For greater clarity, the Regulations will create a new definition of an MDI within the MDR, for the purposes of the Act that will explicitly state:

Given that one of the elements within the definition of SADR includes a requirement for “in-patient hospitalization or prolongation of existing hospitalization,” this was the rationale for focusing on hospitals for reporting. Documented information about an SADR or MDI could include, for example, a serious adverse reaction/incident that is identified in a patient’s clinical record, or a separate reporting form (electronic or hard copy) that has been completed by a health care professional. There will be no need to perform a causality assessment to determine whether a therapeutic product caused the SADR/MDI in order to send an SADR/MDI report to Health Canada. This approach aligns with international best practices for such reporting.

When considering options on the types of reportable reactions/incidents, Health Canada sought to balance the desire to increase reporting rates with the need to minimize operational impacts on hospitals. Health Canada had initially considered limiting ADR reporting to reactions that are both serious and unexpected (i.e. an SADR that is not identified in nature, severity and frequency in the risk information set out on the label of the drug, including information set out on the product monograph) as a means of limiting reporting to circumstances that are a higher priority for product safety monitoring. However, such an approach could potentially screen out information deemed clinically significant by health care professionals that would be valuable in monitoring therapeutic product safety.

Therefore, the regulations will require the reporting of SADRs and MDIs. This approach is expected to result in a significant increase in the number of reports generated by hospitals, and to enhance the amount of information available to Health Canada to identify potential safety risks and improve product safety. Such an approach is also expected to simplify the reporting process.

Types of therapeutic products

This new reporting requirement applies specifically to SADRs and MDIs that involve therapeutic products. Vanessa’s Law defines a “therapeutic product” as “a drug or device or any combination of drugs and devices, but does not include a natural health product within the meaning of the Natural Health Products Regulations.”

Health Canada interprets “drug” under the Food and Drugs Act to include pharmaceuticals (prescription and non-prescription), biologics (including vaccines), radiopharmaceuticals, cells, tissues and organs, blood and blood components, semen, and disinfectants.

While new reporting requirements for SADRs would ideally apply to all types of drugs to maximize the amount of safety data provided, Health Canada is of the view that it would be excessively burdensome to apply these requirements in those cases where a product type is already subject to some form of adverse reaction reporting requirements by either health facilities or health care professionals.

As the mandatory reporting of adverse reactions to drugs such as cells, tissues and organs, blood and blood components and semen is already required for certain types of health facilities through other federal regulations, Health Canada is not putting forward regulatory amendments related to these product categories.

Similarly, drugs and devices that are regulated under clinical trial and Special Access Program (SAP) frameworks have separate reporting schemes in place. Therefore, these categories of drugs and devices are excluded from these new reporting requirements.

For drugs regulated under Part C, Division 10 of the FDR (i.e. those set out in the List of Drugs for an Urgent Public Health Need), the Regulations currently contain SADR reporting requirements that are similar to the requirements outlined in this proposal. To avoid confusion and redundancy for health care institutions, Health Canada will repeal the requirements under Division 10 to align the reporting requirements. This will mean that, as part of an SADR report related to a drug for an urgent public health need, hospitals will have to provide some information that was previously not a requirement, such as a patient’s age and sex, the date on which the patient first used the drug, the date on which the SADR first occurred, any medical condition of the patient that directly relates to the SADR, any concomitant therapeutic products used by the patient, and the result of the SADR on the patient’s health.

In determining whether to require mandatory reporting for vaccines, Health Canada took into consideration that, as part of provincial immunization programs, adverse events following immunization (AEFI) are reported to local health units, so that medical officers of health can monitor local programs. These reports are also forwarded to provincial health authorities, as well as to the Public Health Agency of Canada, for national collation and analysis. The Public Health Agency of Canada shares the data in these reports with Health Canada, enabling regulatory action where appropriate.

Health Canada is of the view that sufficient SADR information related to vaccines administered under a routine immunization program of a province or territory is captured through the current AEFI reporting network, and that this information is currently being provided to Health Canada. Requiring the mandatory reporting by hospitals for SADRs related to these vaccines will result in a duplication of reporting for this class of therapeutic products. In light of the established AEFI network that monitors vaccine safety, and given that AEFI reporting is mandatory for health care professionals in most provincial and territorial jurisdictions, these vaccines will be exempted from the scope of the reporting requirements as they are administered under a routine immunization program of a province or territory. The regulations will still apply to other types of vaccines that are used outside of routine immunization programs.

Therefore, the regulations will require the reporting of SADRs and MDIs associated with the use of pharmaceuticals (prescription and non-prescription), biologic drugs (excluding vaccines that are part of a routine immunization program), radiopharmaceuticals, disinfectants and medical devices.

Consideration was given to limiting the reporting requirements to a targeted subset of higher priority products. However, this option was viewed as undesirable as such a requirement would likely mean missing important reporting opportunities and would be unnecessarily time-consuming given that hospitals would have to allocate resources to verify whether a product is reportable.

Required information

The regulations specify the information (such as the name of the hospital and contact information, the name of the drug or device, a description of the SADR or MDI) that must be included as part of an SADR and MDI report, with additional information to be provided if it is known by the reporting hospital.

The success of the SADR/MDI reporting system at Health Canada depends on the quality, completeness, and accuracy of the information submitted. In developing the proposal, Health Canada considered outlining the information to be reported in guidance rather than explicitly in regulations; however, it was thought that such an approach was unlikely to lead to the quality of reporting necessary to contribute to the level of safety monitoring envisioned under Vanessa’s Law. Health Canada will therefore require that specific information be included in reports so that the quality of information received better supports the overall objective of therapeutic product safety monitoring.

Timelines for reporting

The regulations specify that hospitals are required to report SADRs and MDIs to Health Canada in writing and within 30 days of first documentation of the reaction or incident at the hospital. Health Canada is of the view that this interval will allow sufficient time for institutions to collect the required information and prepare high quality reports, while still providing the information to the Department in a useful time frame from a safety monitoring perspective.

Consideration was given to aligning the reporting time frame with the 15-day requirement that currently exists for drug manufacturers to report SADRs under the FDR, or to extending the time frame beyond 30 days. In arriving at a 30-day timeline for hospitals, Health Canada considered the extra time likely required by hospitals to gather and validate information related to the observed reaction or incident, as well as to prepare the high-quality clinical documentation that supports product safety monitoring, while avoiding potential disruptions to the delivery of care. By contrast, manufacturers are responsible for submitting information that has already been compiled and made available to them by the primary source (e.g. health care professionals, patients). Taking these factors into consideration, Health Canada is of the view that the 15-day reporting time frame is reasonable when applied to manufacturers, and that applying a similar time frame would not properly weigh the unique operational challenges faced by hospitals, nor the work that hospitals may need to undertake to compile reports.

Benefits and costs

The full cost-benefit analysis (CBA) report is available upon request.

The CBA seeks to explain the qualitative and quantitative costs and benefits of the regulations. The data was collected from costing surveys distributed to health care institutions, technical discussions with institutions and patient safety experts, Health Canada databases, a literature review of studies conducted in Canada and internationally, and stakeholder feedback received following prepublication of the amendments in the Canada Gazette, Part I. All calculated costs and benefits have been calculated over a 10-year period, and the present value figures have been discounted by 7% as required by the Treasury Board Secretariat. footnote 4

Cost-benefit statement

There are approximately 775 hospitals in Canada footnote 5 that are expected to be subject to the reporting requirements. The projected costs, analyzed further below, include the cost of hospital staff time to collect information (that is in a hospital’s control) about the SADRs and MDIs documented, and to compile the report to send to Health Canada. The total reporting cost to hospitals is expected to be an average annual cost of $73,257,557, which translates to a present value cost of $514,629,670 over 10 years. It is also expected to cost Health Canada $1,210,507 annually to process and assess the reports. As a result, the total net present value cost to the regulations is estimated at $523,131,537 over a 10-year period, discounted at 7%. While the regulations have a net cost, the qualitative benefits, including enhancing the Department’s ability to improve product safety, rationalize the requirements.

Table 1: Cost-benefit statement (in 2018 dollars)

Stakeholder

Base year
Year 1

Final year
Year 10

Total (PV)

Annual
average table 1 note *

Quantitative impacts

Salary to health care professionals

Hospitals

$35,677,957

$35,677,957

$250,587,040

$35,677,957

Training

Hospitals

$9,908,929

$9,908,929

$69,596,168

$9,908,929

SOP revisions

Hospitals

$427,366

$0

$399,408

$42,737

Administrative personnel salary cost

Hospitals

$27,627,935

$27,627,935

$194,047,054

$27,627,935

Review and assessment

Government

$1,210,507

$1,210,507

$8,502,091

$1,210,507

Total costs

$74,852,693

$74,425,327

$523,131,761

$74,468,064

Qualitative impacts

Benefits:

Greater confidence in the safety of marketed therapeutic products on the Canadian market.

Avoided costs to the health care system due to anticipated decrease in number of SADRs and MDIs.

Avoided loss of productivity due to expected decline in the number of people admitted to emergency departments or hospitalized for treatment of SADRs and MDIs.

Changes in health care professionals’ prescribing behavior and better information for patients as a result of better information about marketed therapeutic products.

Table 1 note

Table 1 note *

Annual average is the sum of costs from year 1 to 10 in current dollars divided by 10.

Return to table 1 note * referrer
Determining the baseline

The estimates for the number of SADRs and MDIs that occur annually in Canada vary widely. Patient safety experts point out that many ADRs and MDIs are never identified by health care professionals and patients, and many more are never reported.

A systematic review of 37 studies from 12 countries indicated that only 1%–10% of all ADRs are ever reported. footnote 6 A further 5 of the 37 studies looked specifically at (in their own words) serious or severe ADRs reported in a hospital setting; these studies indicated the median under-reporting rate of serious and severe ADRs is approximately 95%.

Health Canada estimates gleaned from technical discussions, survey responses, and a literature review of Canadian and international sources (scaled to the Canadian population), ranged from a low of 33 500 footnote 7 to a high of 7 230 938 footnote 8 for the number of SADRs to be expected in Canada annually. The annual trend report from Health Canada’s Canada Vigilance Database footnote 9 indicates that voluntary reporting in the past five years averaged 7 692 ADRs per year. Further examination of this data shows that 74% of the reports identified were SADRs, and, out of this figure, about 70% were reported by physicians, pharmacists, and other health care professionals. Based on these numbers, it is estimated that the average voluntary reports for SADRs is about 4 000 cases per year. It is also assumed that these SADRs were reported by health care professionals and were therefore likely to have resulted in a trip to the emergency department (ED).

Using the median under-reporting rate of 95% as suggested through literature review, and the estimated number of voluntary reports made, Health Canada estimates 73 058 ED visits per year are caused by SADRs. Health Canada notes that the 95% under-reporting rate is based on older literature (ranging between 1992 and 2004). Further, the definition of seriousness and severity in these studies may not be consistent with the Health Canada definition, and the methods of collecting data in each study may have varied as well. As a result, the under-reporting rate reflected in these studies may be overestimated. However, in the absence of more current data, Health Canada used this theoretical under-reporting rate as the basis for the cost analysis.

Similarly, some literature reviews footnote 10 suggested that SADRs experienced by patients already in hospitals represent approximately 0.4% of the total hospital admissions. Based on the Canadian Institute for Health Information (CIHI) 2016–2017 Discharge Abstract Database, footnote 11 the total number of in-patients was about three million for that time period. Therefore, it is estimated that there are approximately 12 600 SADRs per year experienced by patients who are already in hospitals. This means a total of 85 658 SADRs per year lead to either a prolongation of hospital stay, hospitalization, or at least a visit to an ED. Health Canada based its cost-benefit analysis on the 85 658 annual report estimate as a likely scenario.

There are a variety of estimates provided that were used to help determine the number of MDIs in Canada. Many MDIs are captured in the literature in broader terms, including critical incidents or medical errors, which make it difficult to estimate the number of MDIs occurring annually. During prepublication of the regulatory proposals in the Canada Gazette, Part I, Health Canada estimated there would be 7 463 footnote 12 MDIs reported annually; however, feedback received from stakeholders following the Canada Gazette, Part I, prepublication suggests that this figure should be much higher. Under the current Regulations, it is mandatory for manufacturers (and importers) to report any incident involving a medical device that is sold in Canada. Health Canada used the average (12 140) of mandatory MDIs reported over five years through Health Canada’s Medical Device Problem Reporting Program as a proxy for the cost-benefit analysis because it is likely the incident occurred either in a hospital or a patient visited a hospital as a result of an MDI. These incidents are currently being reported by the manufacturers (and importers), and under these new Regulations, it is assumed that at least this many incidents will be reported by the hospitals.

Costs to hospitals

The regulations place the responsibility of reporting on hospitals. Data from the CIHI combined with Health Canada’s own estimates indicates that there are about 775 hospitals operating in Canada. The regulations will apply to these organizations and it is assumed there may be efficiencies of scale gained as standard operating procedures (SOPs) and education modules can be shared among organizations. Further efficiencies will likely be gained if provinces and territories centralize functions for reporting; however, efficiency gains are not within the scope of this analysis. While the regulations apply to approximately 775 hospitals, the activity of reporting is shared with health care professionals, and front-line staff who will be involved in documenting the SADR or MDI, including collecting and validating the information to be included in a report to Health Canada. Costs associated with these health care professional activities have been included in this analysis.

Through stakeholder feedback, it was suggested that it takes approximately four hours of staff time for a single SADR report or MDI report. Since an SADR report may require a physician or a pharmacist to complete the report, Health Canada used the average earning rates footnote 13 between a physician and a pharmacist which is approximately $86 per hour for an SADR, and a registered nurse rate of $69 per hour for an MDI. Based on this data, Health Canada estimates that the salary cost to hospitals will be $35,677,959.

Table 2: Anticipated salary costs to hospitals (in 2018 dollars)
 

Cost per report

Number of reports

Additional annual salary

Salary cost of health care professionals, SADR

$374

85 658

$32,034,379

Salary cost of health care professionals, MDI

$300

12 140

$3,643,578

Total salary

    

$35,677,957

Note: Average cost per report for an SADR is $373.98 and an MDI is $300.13.

In addition, institutions indicated that annual training will be required for front-line staff at a cost of $12,800 per year per hospital; they also estimated a one-time cost of updating existing standard operating procedures at $550 per institution. Since it is front-line staff who would likely be involved in preparing and submitting the information to Health Canada, these activities have been factored into the total cost to institutions. The survey responses and technical discussions suggested that the cost per SADR or MDI report is $280. The cost of reporting is directly related to the total number of reports made. This cost may be brought lower if hospitals develop an electronic reporting system that facilitates the transfer of information to Health Canada.

Table 3: Administrative personnel salary costs of SADR and MDI (in 2018 dollars)
 

Cost per report

Number of reports

Total cost of reporting

Administrative personnel salary cost, SADR

$283

85 658

$24,198,385

Administrative personnel salary cost, MDI

$283

12 140

$3,429,550

Total salary

    

$27,627,935

Note: Average cost of reporting is $282.50.

The expected cost of reportable SADRs is $24,198,385, and the cost of reportable MDIs is $3,429,550 per year.

Total costs to health care institutions are calculated to be $73,642,187 in the first year, with an annual cost of $73,214,821 each year after (assuming a constant rate of reporting), with a present value cost of $514,629,670 over 10 years at a discount rate of 7%.

Table 4: Total cost to health care institutions (in 2018 dollars)
 

Year 1

Year 2 to 10

Present value costs

Annual average table 4 note *

Salary to health care professionals

$35,677,957

$35,677,957

$250,587,040

$35,677,957

Training

$9,908,929

$9,908,929

$69,596,168

$9,908,929

SOP

$427,366

$0

$399,408

$42,737

Administrative personnel salary cost

$27,627,935

$27,627,935

$194,047,054

$27,627,935

Total costs

$73,642,187

$73,214,821

$514,629,670

$73,257,557

Table 4 note

Table 4 note *

Annual average is the sum of costs from year 1 to 10 in current dollars divided by 10.

Return to table 4 note * referrer

Government costs

The cost to Health Canada to review the increased SADR and MDI reports could potentially be as high as $1,210,507 annually. This cost represents the additional 15 full-time equivalents (FTEs) who could be needed to process and assess the anticipated increase in reporting, assuming a compliance rate of 100% and a theoretical under-reporting rate of 95%. However, the actual cost will likely be far lower than this because it is difficult to determine how many additional reports Health Canada will actually receive. Moreover, this cost is anticipated to further reduce with efficiency gains that are expected to be realized with the introduction of a new database for MDIs and upgrades to Health Canada’s existing database for ADRs, as well as internal process changes. The actual cost to government will be managed through redistribution of workload and reallocation of resources within the Department.

Qualitative benefits of the regulations

Following an analysis of comments submitted during the publication in the Canada Gazette, Part I, Health Canada made adjustments to the presentation of anticipated benefits. Furthermore, literature review and technical discussions identified a significant amount of indirect benefits; Health Canada has opted to describe these benefits qualitatively.

The following benefits are identified as resulting from the regulations; however their impacts are non-quantifiable:

i. Greater confidence in the safety of marketed therapeutic products on the Canadian market

The regulations will increase information for Health Canada to identify potential safety risks, thus enhancing the Department’s ability to improve product safety; this is expected to result in greater consumer confidence in the safety of marketed therapeutic products on the Canadian market.

ii. Avoided costs to the health care system

There is a greater risk for ADRs for seniors due to the number of drugs they take. This is a significant issue since the treatment of seniors in hospital has been calculated to be more expensive than for non-seniors ($452 for seniors and $304 for non-seniors). footnote 14 Furthermore, it is estimated that 20% of ED visits due to an SADR led to a hospitalization that lasted 7.7 days on average. footnote 15 Literature reviews also indicated about 0.4% of total hospital admissions experience SADRs,footnote 16 prolonging their stay by 3.6 days on average at a cost of about $900 per day.footnote 17 These are the direct costs borne by the health care system every year as a result of SADRs.

A literature review, as well as technical discussions held by Health Canada with patient safety experts, suggests that indirect benefits from the regulations will be realized, with some critical assumptions. First, it is assumed that health care professionals will document the SADRs and MDIs observed so that hospitals can report these in accordance with the regulations. Second, it is assumed that the information gathered from the hospital reports will contribute to an improved ability for Health Canada to assess the real-world safety of drugs and medical devices and to take corrective regulatory action as necessary. The outcomes of departmental actions such as risk communications and/or label changes would be used to provide health care professionals and patients critical information on drugs and medical device product safety. With this knowledge, health care professionals are expected to change their prescribing behaviour or provide patients with up-to-date information about the risks and benefits associated with drugs and medical devices, thereby reducing the number of SADRs and MDIs occurring in Canada each year.

iii. Avoided cost to the Canadian economy from loss of productivity

Treatment of SADRs carries a further indirect cost to the Canadian economy of lost productivity due to time spent either in the ED and/or an extended hospital stay. The information collected by Health Canada through these regulations will contribute to a better understanding of the risks and benefits of drugs and devices, and this understanding will inform the corrective actions taken by the Department, as required. Corrective actions have the potential to reduce the number of people admitted to the ED due to an SADR or an MDI and in-patients experiencing an SADR or an MDI, thereby reducing the cost of lost productivity.

“One-for-One” Rule

The purpose of the “One-for-One” Rule is to strictly control new administrative burden on business resulting from regulations. The “One-for-One” Rule does not apply as there is no impact on business.

Small business lens

The small business lens applies to any regulatory proposals that impact small business and have a nationwide cost impact of over $1 million annually. The Treasury Board Secretariat defines a small business as any business, including its affiliates, that has fewer than 100 employees or less than $5 million in annual gross revenues.

The small business lens does not apply, as there are no impacts on businesses.

Consultations prior to prepublication in the Canada Gazette, Part I

In developing the regulations, Health Canada sought input since early 2015 from health care institutions, health care professionals, advocacy groups, provinces and territories, other stakeholders, and the public on the issue of mandatory reporting by health care institutions.

As part of these activities, an issue identification paper was published in April 2016 to solicit early views on the issue of mandatory reporting. Based on feedback received through the issue paper, Health Canada prepared a consultation paper entitled Toward Mandatory Reporting of Serious Adverse Drug Reactions and Medical Device Incidents by Health Care Institutions (PDF). The purpose of the consultation paper was to describe various policy options under consideration by the Department and to seek advice on the parameters of the regulatory proposal. The paper was published online on June 28, 2017, for a 45-day public consultation period which ended on August 11, 2017. A broad range of stakeholders provided comments during this consultation period.

As a follow-up to these consultation activities, and to support the cost-benefit analysis process, additional technical discussions were held in December 2017 and January 2018. These technical discussions involved a representative sampling of key hospital staff (e.g. chiefs of staff, heads of pharmacy, officials responsible for records and IT) across a range of hospitals, and patient safety advocacy groups, with the goal of gathering front-line views on the likely impact of mandatory reporting on the day-to-day work within a hospital setting. The technical discussions also provided a venue to discuss and validate evolving policy considerations with stakeholders.

While there have been mixed responses from stakeholders regarding some of the details of the regulatory proposal, particularly regarding the parameters of the regulations, the overwhelming majority of respondents are strongly in favour of the objective and key principles of the regulations for mandatory reporting of SADRs and MDIs by hospitals.

Applicable health care institutions

The consultation paper proposed that reporting requirements apply only to hospitals that provide acute care services, but some stakeholders were confused about how “acute care services” would be interpreted. While there was strong support among health care institutions and health care professionals for Health Canada’s proposal, approximately a third of respondents from across stakeholder groups recommended broadening the scope of health care institutions to improve information acquisition. In light of this feedback, Health Canada expanded the scope of the regulations to require reporting from all hospitals.

Types of reportable reactions and incidents

The consultation paper proposed that ADR reporting be limited to reactions that are both serious and unexpected, while MDI reporting would encompass all serious incidents. The proposal to require only the reporting of serious and unexpected ADRs was meant to focus on reactions and incidents that are the highest priority targets for product safety monitoring. The mandatory reporting of all SADRs was considered at the time to have the potential to impact hospital operations in a more significant way, and was therefore thought to be a less attractive option.

Through responses to the consultation paper, there was strong support across stakeholder groups for limiting reporting to serious and unexpected ADRs, although approximately a third of stakeholders supported broadening mandatory reporting to encompass all SADRs. Results from the technical discussions with front-line experts suggested further support for broadening the reporting requirement to all SADRs. Stakeholders that supported expanding the scope in this way suggested that such an approach could increase the amount of information available to identify potential safety risks, as well as simplify the process of determining whether an SADR or MDI is reportable. In light of these views, Health Canada expanded the scope of reporting in the regulations to include all SADRs and MDIs for the prescribed therapeutic products.

Stakeholders also expressed some concern about needing to establish causality between a certain therapeutic product and an SADR or MDI. Health Canada will ensure that guidance, education and outreach conveys to hospitals and health care professionals that the information to be submitted by the hospital to Health Canada only has to represent the suspicions of the documenting health care professional that an SADR or MDI has been observed. There would be no need to perform a causality assessment to determine whether a therapeutic product caused the SADR or MDI in order to send an SADR or MDI report to Health Canada. This approach regarding establishing associations is in line with international best practices for ADR reporting.

Types of therapeutic products

The consultation paper proposed to limit the scope of the mandatory reporting requirements to information about pharmaceuticals (prescription and non-prescription), biologic drugs (excluding vaccines), radiopharmaceuticals, disinfectants and medical devices. Certain therapeutic products were proposed to be excluded from the proposed mandatory reporting requirements, as these products are already subject to reporting requirements either by health facilities or health care professionals under other regulatory frameworks.

There was notable support for this position; nevertheless, many respondents suggested that the scope should be broader and extended to include natural health products (NHPs) and/or vaccines. However, natural health products cannot be included within the scope of this regulatory proposal, as a “therapeutic product” was defined under Vanessa’s Law to be “a drug or device or any combination of drugs and devices, but does not include a natural health product within the meaning of the Natural Health Products Regulations.” Health Canada continues to encourage health care institutions, practitioners and consumers to voluntarily report issues involving natural health products.

With respect to vaccines, most provincial and territorial jurisdictions have mandatory reporting regimes in place for health care professionals to report adverse reactions following immunization. There are also established provincial and federal networks to monitor immunization program vaccine safety. Health Canada considered the potential for duplication and unnecessary burden on hospitals, and decided that vaccines administered under a routine immunization program of a province or territory will be exempt from the reporting requirement.

Required information

There was significant support for Health Canada’s proposal to require hospitals to report certain information about SADRs and MDIs if the information is in the control of the hospital. This information included: name of the hospital, contact information for a representative of the hospital, identifying information for the drug and/or medical device, a description of the SADR or MDI; and in the case of an SADR, the age and sex of the patient.

Timelines for reporting

There was significant support for Health Canada’s proposal for a 30-day reporting time frame. Some drug and medical device industry respondents commented that reporting timelines for institutions should align with the 15-day reporting timelines that exist now for drug manufacturers under the FDR. Health Canada is of the view that such a timeline would represent an unnecessary burden given the operating conditions of many hospitals. The 30-day time frame strikes a balance between timeliness and operational viability.

System consultations

On March 23, 2018, Health Canada sought feedback from external stakeholders, including hospitals, health authorities, and provincial and territorial health representatives to determine opportunities to leverage current processes and/or systems that are already in place to facilitate the implementation of mandatory reporting on SADRs (as defined in the FDR) and MDIs (as described in the MDR). The online questionnaire was posted and available for comment for 43 days from March 23, 2018, to April 20, 2018.

Summary of comments received during prepublication in the Canada Gazette, Part I

The proposed Regulations Amending the Food and Drug Regulations (Serious Adverse Drug Reaction Reporting — Hospitals) were prepublished in the Canada Gazette, Part I, on June 16, 2018. The proposed regulations, as well as a draft guidance document, were open for a 75-day comment period (June 16–August 29, 2018) during which the Department received comments from 29 respondents for the regulations and 12 comments for the guidance document. Respondents included associations representing pharmacists and pharmacy regulatory bodies, the therapeutic products industry, health care institutions, health care professionals, institution associations, patient safety advocates, academia, provincial ministries of health and private citizens.

Overall, respondents were supportive of the proposal. A number of comments received were outside of the scope of the proposal and are not considered here, but all comments were directed towards the appropriate government officials.

Although widely supportive, some respondents expressed concern around potential operational impacts and associated costs of the regulatory proposal. Some of the common concerns centred on the types of reportable reactions, specifically the requirement to report all SADRs versus reporting only serious unexpected ADRs. Some respondents proposed that reporting requirements should extend beyond hospitals to, for example, long-term care facilities, retirement homes, and clinics. One health care provider expressed concerns around the data fields, i.e. additional mandatory fields should be included to make the reports more complete. There were some concerns with regards to the timeline, where respondents raised that the 30-day reporting time frame is insufficient, especially in the case of MDIs, where it can take longer than 30 days to investigate. Some respondents suggested that the implementation period should be extended from six months up to two years. Other general comments received were specific to clarifying certain elements and wording of the regulations for greater clarity, including in the guidance document, and the need for continued outreach and education. The comments received are grouped according to the issue and discussed in greater detail below.

Types of ADRs

While there was some support for reporting all SADRs, a considerable number of respondents from hospitals and institution associations expressed concern with the need to report all SADRs versus reporting only serious unexpected ADRs. Respondents questioned the value of having to report SADRs that are well-known and already identified in the product labelling such as bone marrow suppression induced by antineoplastic agents. Stakeholders were concerned that the requirement to report all SADRs would have a significant impact on resources and would take away from the amount of time dedicated to patient care. At least one institution association suggested that the time, effort and expense would be better served managing the drug therapy of patients rather than reporting well-known ADRs. Another respondent commented that having to report well-known SADRs will create unnecessarily large databases which will ultimately compromise the timely analysis needed for serious unexpected ADRs.

Health Canada’s database is capable of handling large amounts of data; therefore, signal detection for new reactions will not be compromised even if there is a large number of reports for well-known reactions. In determining the scope of reportable SADRs, the Department sought to find a balanced approach. If mandatory reporting were limited to only unexpected SADRs, this would likely be too narrow from purely a product safety perspective. Reporting all SADRs will help ensure that Health Canada has sufficient information to detect new safety signals for drugs. In Health Canada’s view, even though a specific adverse reaction may already be known for a product, additional information on the frequency and severity can help to better inform the product’s safety profile.

The Department is of the view that proceeding with the regulations to report all SADRs, and not limiting the scope to unexpected SADRs will help to ensure that the intent of the new regulations, i.e. to enhance the quality and quantity of SADR reports, is met. The regulations will also help ensure that Health Canada has sufficient information to monitor emerging product safety issues, including changes to the frequency or severity of reactions already reflected in the product label.

To address confusion among some stakeholders regarding what constitutes “seriousness” in the context of an SADR, the guidance document accompanying the regulations has been revised to provide more clarity on this issue, including examples of what Health Canada considers to be “serious” and “non-serious” ADRs.

Applicable health care institutions

While stakeholders were generally supportive of the reporting requirement to include all hospitals, a number of respondents suggested the proposal should include health care institutions outside of the definition of “hospital” in order to capture SADRs and MDIs that occur outside of a hospital setting. One respondent, who advocated for the inclusion of long-term care (LTC) facilities, suggested that seniors are at an increased risk of SADRs due to polypharmacy (patients on multiple medications) and inappropriate prescribing. The respondent noted that patients who die in LTC facilities or nursing homes, where significant occurrences of SADRs occur, would go unreported if the patient is not transferred to a hospital. A health care professional association noted that the reporting of SADRs that resulted in death outside of a hospital should be mandatory.

Hospitals will be subject to the mandatory reporting requirement because Health Canada is of the view that hospitals are most likely to treat patients presenting with SADRs or MDIs. The definition of SADR in the FDR includes a requirement for “in-patient hospitalization or prolongation of existing hospitalization.” LTC institutions that are not hospitals will not be subject to these regulations as the vast majority of SADRs or MDIs that occur at LTC institutions and other non-hospital facilities should be captured when patients are transferred to a hospital for treatment. Furthermore, information about patient outcome is a key piece of information that hospitals should be able to provide in most cases, while other facilities may not always have this information. Nevertheless, Health Canada encourages voluntary reporting, including from LTC facilities, and will monitor the data received to inform future modifications to the regulations where needed.

Health Canada is of the view that polypharmacy and other age-related confounding factors, such as multiple medical conditions, may make it difficult to determine the causality of SADRs; thereby making specific signal detection difficult. While being cognizant that polypharmacy in the elderly may present complications to signal detection, the Department is aware that there is value in obtaining SADR reports from vulnerable geriatric populations. Given that the definition of “hospital” in the current regulations includes hospitals that specialize in chronic and extended care, there is information that the Department can gather on some LTC institutions that are within the scope of the definition of “hospital.” By analyzing the SADR reports that are received from these types of hospitals that treat elderly population groups, Health Canada can further inform its decision-making with respect to improving medication safety for these vulnerable populations.

The Department is aware that under the current regulations, the SADR-related deaths of patients who are not transferred to a hospital will not be captured, and investigation into the drugs causing the SADR will go undetected. Health Canada is examining ways to address this issue, including outreach and education efforts outside of hospitals (including coroners’ offices) to encourage voluntary reporting in these circumstances.

On December 20, 2018, Health Canada published an Action Plan on Medical Devices: Continuously Improving Safety, Effectiveness and Quality, which outlines the actions that Health Canada is taking to improve the safety and effectiveness of medical devices and to optimize health outcomes for patients. In addition to mentioning the regulations under Vanessa’s Law for the mandatory reporting of MDIs, the Action Plan also details some of Health Canada’s actions to improve reporting from health care facilities besides hospitals (e.g. LTC facilities, clinics, etc.). These include efforts to expand the Canadian Medical Devices Sentinel Network (CMDSNet), which is a network that facilitates the voluntary reporting of MDIs. Created in 2009, CMDSNet currently covers 17 health care organizations, representing more than 260 hospitals and facilities across the country. Furthermore, the Action Plan describes Health Canada’s implementation strategy for an education and promotion program aimed at improving the reporting of MDIs from other health care delivery sites.

Therapeutic products

A few respondents suggested that the regulations should be expanded to include natural health products and cannabis for medical or non-medical purposes. Drugs containing cannabis are captured by the regulations. The other product categories are outside the scope of legislative authorities conferred by Vanessa’s Law; therefore, these products will remain out of scope of the regulations. However, Health Canada continues to encourage hospitals to voluntarily report suspected reactions involving natural health products and cannabis other than drugs containing cannabis.

Required information

Subsection 62(2) of the MDR prescribes information that a hospital is required to provide to the Minister about a MDI. More specifically, paragraph 62(2)(b), as published in the Canada Gazette, Part I, required that the name of the device and its identifier be provided. The Department has reconsidered its approach, and has decided that the required information in this subparagraph will be replaced with a more flexible requirement for the “name of the device or its identifier” as it may be difficult for a hospital to have all the information required under paragraph 62(2)(b). In the case where a hospital does not have in its control both the name of the device and its identifier, the Department revised the regulations to allow hospitals to submit either information that would aid in identifying the device.

The regulations have been amended to exempt a hospital from sending a MDI report to Health Canada if the hospital does not have, in its control, all the information in the list below:

Health Canada is of the view that this change is necessary to mitigate the risk of a hospital not reporting a MDI to the Department by limiting the exemption from mandatory reporting to the situation where the hospital does not have, within its control, the name of the device or its identifier and a description of the MDI. The reason for exempting the hospital from having to report MDIs if it does not have the key pieces of information above is that these pieces of information are necessary for Health Canada to conduct a basic assessment of these reports.

The Department also decided that the date of first documentation of the SADR and the MDI be added as a data element in C.01.020.1(2)(g) of the FDR and subsection 62(2) of the MDR, respectively, so that Health Canada may be able to identify duplication and assess hospital compliance with the 30-day timeline for sending SADR and MDI reports. Health Canada has considered the date of first documentation to be necessary as it would be a way to identify instances in which the Department received the same report from the same source (i.e. hospital) or another source such as a Market Authorization Holder (MAH) more than once. The regulations have been amended to reflect that change.

Timelines

While some respondents expressed concern with the 30-day reporting period, overall, the vast majority of respondents believed a 30-day reporting timeframe was sufficient. Some of those advocating for a longer timeline, stated that 30 days to report a MDI was insufficient as it often takes longer to complete an investigation. One respondent suggested a 45-day reporting timeframe for MDIs due to the more complex nature and long investigative timeframe required to properly investigate MDIs. A health care professional commented that many investigations that involve the vendor take longer than 30 days. In proposing the 30-day reporting timeframe, Health Canada took into account the unique operational challenges faced by hospitals and the work that hospitals may need to undertake to compile SADR and MDI reports. Health Canada is of the view that this timeframe will allow sufficient time for institutions to collect the required information and prepare high quality reports.

In the draft guidance document that was published in July 2018, it was noted that, while Health Canada requires SADRs and MDIs to be reported within 30 calendar days, a follow-up report can be submitted if the hospital becomes aware of additional information or needs to correct information previously submitted in a report. The revised version of the guidance document outlines the processes for submitting follow-up reports.

Resource implications

A number of respondents raised concerns with the additional resource implications they would incur to comply with the regulations. Primary issues cited were that the proposal would result in increased workload and expenses (hiring additional staff) due to mandatory reporting, as well as other more technical aspects such as training, system and policy changes which all would have a significant impact on resources. Some respondents indicated that institutions would have difficulty coping with the increased workload. A health care professional association commented that the requirement will add to already heavy workloads and hospitals may be required to divert personnel from direct patient care to reporting.

While some respondents stated that the Department may have underestimated the administrative burden required to be in compliance with the regulations, others were of the view that the issue of administrative burden would be minimal. Health Canada considered the unique operational challenges faced by hospitals, and the work that hospitals may need to undertake to compile SADR and MDI reports, and is confident that the potential benefits of the regulations outweigh the burden to comply with these regulations. Since the reporting obligation is placed on hospitals and not on physicians, the institutions can create structures that would allow them to meet the regulatory requirements while minimizing impact on resources.

Reporting process

A number of respondents noted that Health Canada will need an accessible, electronic and efficient reporting system. Two respondents from a health care institution commented that the reporting system needs to build on existing reporting systems or infrastructure and should be electronic.

A respondent from a health care institution suggested that Health Canada should align its reporting system with existing programs in hospitals and provided the existing ADR form as an example. There was also a suggestion that Health Canada develop an electronic form that would be integrated with current reporting databases. Another comment centred on the need to design a mandatory reporting tool that is easy to use. Health Canada greatly appreciates the comments received specific to the design of the reporting system and has carefully considered them and concluded that, at this time, there will not be a single system for reporting due to the variety of reporting systems currently in use among provinces and territories. To provide the greatest flexibility for hospitals and to allow them to use their existing systems and processes, Health Canada will be able to receive reports via various submission methods and formats and hospitals will be able to select the most efficient ones for their circumstances. Hospitals are encouraged to seek opportunities to leverage their existing databases (e.g. incident databases, electronic health records) to create efficiencies to facilitate reporting and Health Canada will continue to be open to collaborate with hospitals towards this goal.

A health authority suggested that there should be a coordinated federal plan to capture and collate the reports. A respondent from the pharmaceutical industry suggested that industry should be involved in developing the reporting forms and identifying which information should be mandatory, to help ensure that they are easy to use and that the required fields portray a complete description of the ADR or MDI. The regulations require hospitals to report serious ADRs and MDIs to Health Canada. Health Canada acknowledges the important role that manufacturers play in monitoring the safety of their products and encourages hospitals to continue to report serious ADRs and MDIs to manufacturers (and importers) for patient safety reasons, as well as to Health Canada. Hospitals are not required under the regulations to report to the manufacturer, but as part of their surveillance activities, manufacturers are expected to consult the Canada Vigilance Adverse Reaction Database and the Medical Devices Online Incident Database to identify reports for their products that were sent directly to the Canada Vigilance Program.

Feedback to hospitals on reports

Concerns centred on the need for a robust and sustainable mechanism to ensure that hospitals (and patients) receive timely feedback; one respondent is of the opinion that feedback will encourage reporting. Health Canada has already taken several concrete steps to improve access to timely, useful and relevant health and safety information, while still respecting privacy, confidentiality and security considerations. The Canada Vigilance Adverse Reaction Online Database contains information about suspected adverse reactions that have been reported from all sources. Similarly, Health Canada recently developed a public-facing, searchable online database for MDIs. The Department also produces a report to provide the annual numbers and trends of adverse drug reaction case reports and medical device incident reports sent to Health Canada. Health Product InfoWatch is a monthly publication intended to alert health care professionals and consumers to potential signals detected through the review of case reports submitted to Health Canada. It is a useful mechanism to disseminate information on suspected adverse reactions to health products occurring in humans before comprehensive risk-benefit evaluations and regulatory decisions are undertaken. Summaries of safety reviews are also posted online. Each summary outlines what was assessed, what was found and what action was taken by Health Canada, if any. Health Canada disseminates findings to health care professionals and the public to alert them about identified health risks related to drugs and medical devices.

Health Canada is currently working with its stakeholders to identify the content, frequency and format of products used to share information from ADR/MDI reporting that will be of most use for health system partners. Materials under exploration include, but are not limited to, educational modules, case studies, infographics and feedback to hospitals. The Department will also refine and optimize the annual trends report to better meet the needs of users, and launched a quarterly webinar series to provide a venue for discussions of ADR and MDI specific issues with target audiences.

It is important to note that any personal information submitted to Health Canada will be protected under the federal Privacy Act, and will not be published or communicated publicly in any way. This includes any information that could be used to identify patients.

Coming-into-force date

A number of respondents expressed concern with the proposed pace of implementation for the regulations, i.e. the 6-month coming-into-force date following publication in the Canada Gazette, Part II. Some respondents proposed a phased-in or pilot project as a more suitable implementation choice. A health care professional suggested that implementation begin with a pilot project among the more engaged hospitals at the outset to allow for system development and testing, and a few months later (4–6 months) the regulations could become enforceable for all. A rationale provided by an institution association in support of this comment is that the current reporting tools are not the same among provinces and some systems are less onerous than others; hospitals in provinces with simpler systems will likely have less difficulty in implementing the regulations than hospitals in provinces with complex systems. To that end, the respondent suggested extending the time between the publication of the regulations and its coming into force, from six months to two  years.

While several respondents advocated for a longer implementation period with a possible phased-in approach, Health Canada paid particular attention in selecting an appropriate coming-into-force date and remains committed to its goal for the regulations to come into effect on December 16, 2019. Health Canada is committed to working with hospitals to help ensure that they have all the information they need and are prepared for mandatory reporting.

Cost-benefit analysis

During the Canada Gazette, Part I, consultation period, 14 comments regarding the CBA were received from stakeholders; the majority of the comments received were from associations representing health care professionals. The majority of respondents expressed concern that the CBA did not accurately reflect the increased costs associated with the implementation of the regulations. A number of stakeholders indicated the CBA was conservative with regards to cost estimates and the number of full-time employees that would be needed to collect, verify and compile information to report to Health Canada, and that the estimates used to calculate the reduction in SADRs and MDIs were not based on actual data, but rather assumed or extrapolated.

Many stakeholders who commented on the CBA expressed concern that the analysis did not accurately reflect the added costs associated with the implementation of the regulations. As a result, Health Canada used supplementary data provided by a health care institution (related to salary and time needed to complete and submit a report) in combination with additional data from Statistics Canada to recalculate the estimated cost to hospitals. Some stakeholders also commented that the literature referenced in the CBA was outdated. As a result, Health Canada performed a second literature search to confirm that the literature referenced in the CBA is the most recent literature available. Health Canada also narrowed the scope of studies used to estimate the under-reporting rate to only those studies which link directly to SADRs and MDIs reporting.

Additionally, a number of respondents were of the view that the data ignores the increased costs for drug companies who will need to undertake additional activities as a result of increased SADR data. Health Canada has considered this point and maintains that the regulations are not anticipated to lead to a spike in costs for manufacturers. Manufactures must undertake remediation activities based on SADR data under certain circumstances regardless; thus, the regulations do not add to the circumstances under which manufacturers have to take these activities. Nonetheless, manufacturers’ concern is now noted in the qualitative section of the CBA as a potential downstream cost. The Department has no way of quantifying this downstream cost.

Some stakeholders also indicated that the analysis ignored the increased costs to the federal government. The Department is aware that the implementation of these regulations will result in a greater cost to Health Canada due to an increase in reports received. This cost could potentially be as high as $1.2 million, representing an additional 15 FTEs needed to review these reports. However, the actual cost impact of the regulations on the Department is likely to be much lower as it is unlikely that hospitals will be able to identify and report 100% of all SADRs and MDIs. Further, efficiency gains are expected to be realized with the introduction of a new database for MDIs and upgrades to the existing database for ADRs. A section on government costs has been added to the CBA. These costs will be managed by the Department through redistribution of workload and reallocation of existing resources.

Guidance document

Twelve respondents provided comments on the guidance document; these included health care professionals, institution associations, the medical device industry, federal and provincial governments and representatives of the pharmaceutical industry. A number of comments received requested clarification to various sections of the guidance document. These comments have been taken into consideration and will be reflected in the final version of the guidance document.

Summary of changes to the regulations following prepublication

The regulations differ from those prepublished in the Canada Gazette, Part I, in the following manner:

Rationale

The regulations are necessary to give effect to section 21.8 of the Food and Drugs Act so that important information from hospitals concerning SADRs and MDIs is available to Health Canada in support of the Department’s therapeutic product safety monitoring. In the absence of these regulations, SADRs and MDIs in hospitals will likely go unreported, potentially compromising public health and patient safety. Mandatory reporting by hospitals will contribute to the overall knowledge base on potential safety issues, and will assist Health Canada in providing health care professionals and patients with better, up-to-date information on product safety.

In drafting the regulations, Health Canada has also worked to minimize operational impacts on hospitals, in accordance with subsection 30(1.3) of the Food and Drugs Act:

As detailed in the sections above, Health Canada has applied this lens in considering each of the factors being framed by the regulations (i.e. applicable health care institutions, types of reportable reactions and incidents, types of therapeutic products, and required information).

The regulations also reflect the outcome of consultation with affected health care institutions, health care professionals, and patient safety experts on the issue of not imposing an unnecessary burden on the health care system.

Implementation, enforcement and service standards

Implementation

Under the regulations, hospitals that are regulated through provincial/territorial legislation and those operated by the federal government have the responsibility to provide reports of SADRs and MDIs to Health Canada. To provide hospitals with time to adjust to the regulations, Health Canada will implement a delayed coming into force as part of implementation. The regulations will come into force on December 16, 2019.

As part of the implementation plan associated with mandatory reporting of SADRs and MDIs, Health Canada will provide guidance, outreach, and education to all hospitals and health care professionals working within hospitals responsible for reporting. Guidance documents, written in plain language, will assist by outlining the type of information that should be submitted and the different methods available for submitting reports. Health Canada is working to develop and implement an educational approach and the content needed to support health care professionals in the identification of SADRs and MDIs and in understanding the importance of documenting complete information related to their observations. Health Canada has multiple mechanisms to share learning from reported ADRs/MDIs (e.g. Canada Vigilance Adverse Reaction Online Database, Health Product InfoWatch) and is currently working with stakeholders to optimize these products.

Hospitals will be able to use the current methods for reporting SADRs/MDIs established under the existing process and system for receiving voluntary reports. Reporting forms are available online, and information can be submitted by fax, email or through a web-based mechanism. Health Canada is also seeking to identify opportunities to facilitate system-to-system transfer of information to minimize the impact on reporting institutions.

Once the reports are received by Health Canada, the Department will perform an initial review of their quality and completeness, the reports will then be processed and further analyzed by scientific staff. Reports will be analyzed to identify potential therapeutic product safety problems or signals. A signal is considered to be the preliminary indication of a product-related issue, and it triggers further investigation to confirm or to disprove a potential association between the product and the reported event. As SADR and MDI reports represent one source of information about possible safety problems with a therapeutic product, they will be used in conjunction with information received by Health Canada from other sources (e.g. information from industry and foreign regulatory agencies, medical literature) as part of Health Canada’s post-market safety assessment work. Should a safety concern be identified as a result of product monitoring, Health Canada could take several possible actions, including continued monitoring, issuing risk communications, requiring label changes, or ordering a recall if the Minister believes that a therapeutic product presents a serious or imminent risk of injury to human health.

Enforcement

The Act allows for a range of enforcement actions to be taken. Building on the activities outlined above, additional compliance and enforcement measures can be taken by the Department in accordance with the risk-based approach detailed in Health Canada’s Compliance and Enforcement Policy (POL-0001). Health Canada’s primary objective in circumstances of non-compliance is to manage the risk to Canadians and to use the most appropriate level of intervention to ensure that a regulated party brings their activities into compliance.

For the purposes of compliance monitoring, Health Canada will implement an oversight mechanism to verify that the reports being received are complete and provide information of sufficient quality to meet the requirements of the regulations. Should issues with reporting quality be identified, Health Canada will work with hospitals to help improve quality and completeness, address any issues that may lead to situations of future non-compliance and bring parties into compliance.

In the event that Health Canada identifies instances of more persistent non-compliance, the Department intends to take a staged approach to working with hospitals to resolve such matters. To start, discussions with the hospital or hospitals will be used to understand the circumstances that led to a situation of non-compliance. Health Canada will then assess these factors and work with regulated parties to identify appropriate follow-up action, such as improving Health Canada guidance, enhancing education and outreach activities, or providing support to hospitals in the development of internal policies and procedures around reporting.

In the unlikely event that a situation of non-compliance is not resolved through this cooperative, staged approach, Health Canada could potentially use provisions of the Food and Drugs Act and its associated regulations, for example, seeking an injunction under section 21.5 of the Act to compel a hospital to comply with the regulations. In determining the appropriateness of exercising enforcement measures, the Department will take into consideration whether the non-compliance of a hospital is shown to pose a serious health risk to Canadians, as well as other factors outlined in POL-0001.

Performance measurement and evaluation

Health Canada will implement the program evaluation requirements of the Treasury Board Policy on Results (Policy on Results) with respect to certain elements of these regulations (e.g. improved quantity and quality of reports) by incorporating relevant performance measurements for internal monitoring and data collection.

Contact

Bruno Rodrigue
Policy, Planning and International Affairs Directorate
Health Products and Food Branch
Health Canada
Holland Cross, Tower A, Ground Floor, Suite 14
11 Holland Avenue
Ottawa, Ontario
K1A 0K9
Address locator: 3000A
Email: hc.lrm.consultations-mlr.sc@canada.ca