Optimizing the Use of Real World Evidence to Inform Regulatory Decision-Making

Health Products and Food Branch Notice

April 16, 2019

Health Canada’s Evolving Approach to Leveraging Real World Evidence (RWE) for Drug Regulatory Decisions

Health Canada is delighted to announce that we are working to optimize the use of RWE for regulatory decisions in order to improve the extent and rate of access to prescription drugs in Canada. This work is being conducted in partnership with key organizations, including the Canadian Agency for Drugs and Technologies in Health (CADTH) and the Institut national d’excellence en santé et en services sociaux (INESSS).

This notice serves to invite industry partners’ submissions using high quality RWE. We encourage RWE submissions (1) that aim to expand evidence-based indications for populations often excluded from clinical trials (ex: children, seniors, and pregnant women); (2) for drugs/diseases where clinical trials are unfeasible such as may be the case with rare diseases; and/or (3) where clinical trials are unethical, as may be the case during emergencies where dosages from animal studies may need to be extrapolated to treat humans potentially exposed to chemical or biological threats.

Health Canada already considers RWE during the pre- and post-market drug regulatory process to inform decision-making. However, our expertise in this area is continuing to evolve as we gain further experience in the assessment of RWE. The Health Canada project on ‘Strengthening the use of RWE for Drugs’ is an initiative under the Regulatory Review of Drugs and Devices which aims to optimize the consideration of RWE across the drug life cycle. To achieve this objective, Health Canada is working collaboratively with key partners, including industry and health technology assessment (HTA) organizations, to establish an approach to using RWE across the drug life cycle that is both systematic and transparent.

To inform drug market authorization decisions, prospectively planned clinical trials have been, and continue to be, considered the most robust tool for providing evidence of drug safety and efficacy. While following specific patient populations in a highly specialized environment facilitates the collection of high-quality controlled data, it can limit generalizability in real world settings. Moreover, conducting clinical trials is not always feasible or ethical for certain diseases/disorders (such as rare diseases) or patient populations (such as children, pregnant women, seniors).

The availability of Real World Data (RWD) has been steadily increasing worldwide and evidence from the analysis of such data can help in the assessment of drug safety, efficacy and effectiveness across the product life cycle. Expanding data and evidence sources to include RWD/RWE may offer new opportunities to gain insight into public health, advance health care, and increase both the extent and rate of drug access for specific patient populations.

To support this work, Health Canada has developed a document on quality of evidence which is attached. It is also collaborating with CADTH and INESSS to develop a joint document on the use of RWE across the product life cycle, to be launched this year.

Lessons learned from this collaborative approach will be shared with partners both in Canada and internationally.

Elements of Real World Data/Evidence Quality throughout the Drug Life Cycle

The quality of the RWE will inform the extent to which Health Canada considers such information sources in regulatory decision-making. There are factors to consider when evaluating quality of evidence, including data reliability and validity, scientific question of interest, study design, statistical methods and analyses, and interpretation of results. The accompanying document entitled “Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle” provides an overview of protocol elements and data quality that should be considered when collecting data and evaluating the quality of RWE.

This document is not intended to be prescriptive. It provides overarching principles to guide the generation of RWE that would be consistent with the regulatory standard of evidence in place in Canada and internationally. Health Canada will update the document as our expertise and experience in assessing RWE evolves.

Development of a Joint Document on the Use of RWE Across the Drug Product Life Cycle

To support access, affordability and appropriate use of drugs in Canada, Health Canada is collaborating with its Health Technology Assessment partners to establish a joint document that will optimize and formalize the use of RWE across the drug life cycle. This commitment originated from a workshop entitled ‘Defining Decision-Grade Real-World Evidence and its Role in the Canadian Context: A Design Sprint’, which took place October 21, 2018, co-hosted by CADTH, Health Canada, the Institute for Health Economics and the Canadian Association for Population Therapeutics.

The full workshop report is available on the Institute of Health Economics Web site. We expect to publish the joint document this year.

Information for Drug Sponsors

All drug submissions, regardless of study design or source of evidence, will continue to undergo rigorous review by Health Canada prior to a final market authorization decision. Sponsors considering using RWE in a drug submission to Health Canada, particularly if it will be used as pivotal evidence, should refer to the ‘Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle’. As noted above, this document is not meant to be prescriptive, but rather to provide guiding principles for a regulatory standard for RWE.
Sponsors filing a drug submission with Health Canada that contains RWE as pivotal evidence within a submission are required to:

• Clearly identify in their cover letter that the submission contains RWE, and in which module(s) of the submission it is included;
• Include a rationale in their cover letter to explain why RWE is being used for the submission rather than more conventional approaches for demonstrating the product’s benefits and risks;
• Include a detailed explanation in their cover letter of how the RWE was gathered and analyzed;
• Demonstrate how any actual or potential biases/confounding in the data collection were mitigated; and,
• Reach out to Health Canada to determine if having a pre-submission meeting, to discuss the RWE proposed as evidence to support market authorization and Health Canada’s data requirements, would be beneficial.

Sponsors filing a drug submission with Health Canada that contains RWE as supporting evidence within a submission are required to:

• Clearly identify in their cover letter that the submission contains RWE, and in which module(s) of the submission is included.

Health Canada acknowledges that RWE has the potential to provide valuable support in areas where controlled clinical trials are not feasible or are challenging to conduct, and will continue to explore the use of RWE to improve Canadians’ access to drugs that are safe and efficacious.

Useful links

• Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle
• RWE for Drugs Project
• Overall R2D2 project

Contact Information

Questions related to the ‘Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle’ should be directed to: hc.mhpd-dpsc.sc@canada.ca

Sponsor inquiries about a potential meeting for a pharmaceutical drug submission that contains RWE as pivotal evidence, should be directed to the Regulatory Project Management Division of the Therapeutic Products Directorate at: hc.rpmd-dgpr.sc@canada.ca

Sponsor inquiries about a potential meeting for a biologic or radiopharmaceutical drug submission that contains RWE as pivotal evidence, should be directed to the Office of Regulatory Affairs of the Biologics and Genetic Therapies Directorate at: hc.bgtd.ora.sc@canada.ca