Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness

Abstract

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied to conditional drug approvals, eligibility criteria and post-market evidence. Our analysis informs recommendations for Canada's proposed regulatory reforms approach to conditional approvals pathways. Our analysis demonstrates that under the current policy, eligibility criteria are insufficiently defined, resulting in their inconsistent application by Health Canada. Regulatory responsiveness to post-market evidence from post-market clinical trial and foreign jurisdiction regulatory decisions is slow and insufficient. In the absence of sufficient regulatory responsiveness, physicians and patients must make clinical decisions without the benefit of the best available evidence. Together, our analysis of the two core tradeoffs in Canada's conditional drug approval provides insight to inform the further development of Canada's proposed agile regulatory approach to drugs and devices that will expand the use of terms and conditions.

European Conditional Marketing Authorization in a Rapidly Evolving Treatment Landscape: A Comprehensive Study of Anticancer Medicinal Products in 2006–2020

“…However, the extent of the benefit/MTA over other medicinal products cannot be assessed. Similar observations have recently been reported for the Canadian counterpart of CMA, the Notice of Compliance with Conditions (NOC/c) 32 . Specific obligations that require (often randomized) postauthorization clinical studies should ultimately resolve these uncertainties and confirm the positive benefit–risk balance.…”

“…Similar observations have recently been reported for the Canadian counterpart of CMA, the Notice of Compliance with Conditions (NOC/c). 32 Specific obligations that require (often randomized) postauthorization clinical studies should ultimately resolve these uncertainties and confirm the positive benefit-risk balance. However, many of the confirmatory trials for the conditionally authorized medicinal products in our study cohort are still ongoing.…”

Information about confirmatory studies required for new drugs conditionally approved by Health Canada: A cross-sectional study

“…At least one-third of the potential information about patient trial characteristics and the benefits and risks of tested treatments was missing [ 11 ]. McPhail and colleagues concluded that eligibility criteria for oncology drugs to qualify for a NOC/c are insufficiently defined, resulting in their inconsistent application by Health Canada [ 12 ].…”

Surrogate Measures of Drug Efficacy—A Finger Pointing at the Moon

“…In addition to better use of Japan’s potentially advantageous requirement for a postapproval reexamination of oncology drugs, every country could make better use of the much-discussed but inadequately implemented concept of conditional approval . Ideally, a regulatory body could use a surrogate measure to give a drug quick provisional authorization for use in a limited way, during which time it would be available but subjected to ongoing study.…”

“…In addition to better use of Japan's potentially advantageous requirement for a postapproval reexamination of oncology drugs, every country could make better use of the much-discussed but inadequately implemented concept of conditional approval. 10 Ideally, a regulatory body could use a surrogate measure to give a drug quick provisional authorization for use in a limited way, during which time it would be available but subjected to ongoing study. After a few years of such use, the systematically collected evidence would be reviewed and a decision made about whether to grant full approval, or, if the drug still has not been shown to provide meaningful clinical benefit, as occurred disturbingly often in the trials reviewed by Maeda at al, 1 its conditional approval could be withdrawn until such time as it can be shown to actually help patients.…”