Health Canada Usage of Real World Evidence (RWE) in Regulatory Decision Making compared with FDA/EMA usage based on publicly available information

Abstract

Purpose: Between January 2020 and December 2021, Health Canada provided a Summary Basis of Decision (SBD) for each of 110 products approved, including 29 oncology products and 21 non-oncology orphan drugs. This review sought to gain insight into how Real Word Evidence (RWE) impacts regulatory decision making. Methods: SBDs for oncology drugs and non-oncology orphan drugs were reviewed for evidence of use of the RWE or historical data to support regulatory decisions. This information was compared with both FDA and EMA reviews. Results: For the 29 Health Canada-approved oncology products, 11 were approved with Notice of Compliance with Conditions (NOCc) status. Two NOCc approvals received extensive RWE reviews, while two other approvals briefly mentioned the use of RWE/historical data. Of the 12 NOC approvals, one received RWE reviews. FDA also approved all 29 drugs, 14 of which received extensive comments on RWE and/or historical data and 8 of which mentioned RWE or historical data. EMA approved 25 of the 29 products and provided extensive comments on 10. Four products received a mention of RWE review. The percentages of submissions with RWE/historical reviews conducted by Health Canada, FDA and EMA were 24.1, 75.9 and 56.0 respectively. Of the 21 non-oncology orphan drugs, Health Canada provided priority review status to 11, with extensive RWE comments in 5 and the mention of RWE in 2 of the regular approvals. Two approvals that used third-party data were not included in the comparison. FDA approved 19, and provided extensive RWE assessment on 5 and mentioned use of historical data in 8. EMA approved 17 and provided extensive RWE and historical comments in 7 and mentioned historical data in 4. The percentages of submissions with RWE/historical reviews by Health Canada, FDA and EMA were 36.8, 68.4 and 64.7 respectively. Conclusions: Use of Real World Data is common among FDA/EMA reviews and Health Canada used RWE in recent NOCc and orphan drug approvals.

Impact of Regulatory Approval Status on CADTH Reimbursement of Oncology Drugs and Role of Real-World Evidence on Conditional Approvals from 2019 to 2021

“…Health Canada Summary Basis of Decision (SBD) database: Health Canada’s database containing summary reviews of all approvals from January 2019 to December 2021 was used as the anchor database [ 20 ] for all products studied in this review article. The review of the SBD database was performed as described previously [ 8 ]. Briefly, the database from 2019–2021 was downloaded into an Excel spreadsheet for abstraction.…”

“…Despite these promising public announcements, a recent publication suggested that Health Canada’s usage of RWE in recent regulatory decision making was low when compared with the usage by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in oncology and orphan drugs. However, an increase in RWE use was observed in Notice of Compliance with Conditions (NOCc) reviews [ 8 ]. The study showed that the majority of conditional approvals were granted to oncology drugs due to the life-threatening and severe nature of these diseases.…”

“…An in-depth review of Summary Basis of Decision (SBD) documents indicated that about 35% of oncology drug reviews mentioned the use of RWE to support efficacy. The publication indicated that Health Canada may have delegated the responsibility of reviewing RWE to CADTH so that RWE would have a more important role in reimbursement decisions [ 8 ]. The current review focuses on the use of RWE by CADTH, the federal agency responsible for making recommendations on drug and medical device reimbursement in Canada outside of the province of Quebec, which has its own reimbursement agency, the Institut national d’excellence en santé et en services sociaux (INESSS) [ 9 ].…”

“…Instead of creating new regulations, Health Canada has utilized existing regulations (both Priority Review and NOCc) to accomplish the same goal [ 14 ]. In 2021, over half of oncology drug approvals were granted NOCc status [ 8 , 15 ]. The approval time frame is shorter than for regular approvals and, more importantly, the data requirement is much lower with approvals being based on the promising nature of the medication for a life-threatening disease rather than on efficacy confirmed by appropriately sized randomized clinical trials.…”

Transferability of real-world data across borders for regulatory and health technology assessment decision-making

“…Randomized controlled trials (RCTs) are the primary source of evidence for regulatory and health technology assessment (HTA) decision-making (1). However, there has been increasing consideration of real-world data (RWD) and realworld evidence (RWE) in the regulatory/HTA decision-making process to complement RCTs and address evidence gaps (2)(3)(4)(5). For instance, a retrospective analysis of single-arm HTA submissions reported that the proportion of submissions that included RWD-based external control arms (ECAs) increased 22% per year over 2015-2019 (6).…”