Introduction to Clinical Trial Data and Health Canada

Confidentiality of Clinical Trial Data

Clinical trial data for new medications is frequently kept confidential, resulting in limited public access to information. A researcher aimed to understand the types of trials that Health Canada accepts by analyzing the characteristics of studies involved in its accelerated approval process.

Market Authorization Process in Canada

For a drug to be marketed in Canada, it must receive market authorization from Health Canada. This process includes submitting a New Drug Submission (NDS), which contains comprehensive preclinical and clinical data regarding the drug’s safety and efficacy. Health Canada’s evaluation of the NDS determines whether a drug is approved. If approved, a Notice of Compliance (NOC) is issued, granting market authorization.

Lack of Access to Clinical Trial Data

Currently, there is no mechanism for accessing the clinical trial data that contribute to the issuance of an NOC. While review reports from Health Canada remain confidential, there have been initiatives aimed at enhancing transparency. Plans are in place to proactively release clinical information for industry-funded trials. The Summary Basis of Decisions project was an initial effort in this direction, but it has faced criticism for inconsistent quality and the exclusion of vital trial details.

Accessing Trial Data through Accelerated Approval

Overview of the Accelerated Approval Pathway

One indirect method to access trial data is through Health Canada’s accelerated approval pathway, established in 1998. This program allows drugs for conditions with limited treatment options to receive a conditional NOC (NOC/c) based on limited evidence of efficacy. Companies granted this approval must conduct confirmatory studies post-approval, with the risk of market removal if these studies fail to validate efficacy.

Dr. Joel Lexchin’s Analysis of Post-Market Studies

Dr. Joel Lexchin from York University conducted an analysis of the characteristics of several post-market studies, with his findings recently published in BMJ Open. He compiled a list of drugs that received an NOC/c since the program’s inception, obtained their qualifying notices from Health Canada, and matched these drugs to studies registered on the US ClinicalTrials.gov website. He then contacted the manufacturers to confirm whether these studies corresponded to the products that received the NOC/c.

Study Characteristics and Methodology Findings

A total of 36 confirmed publications were analyzed for their study characteristics and methodologies. Approximately 80% of these studies were randomized controlled trials, while the remainder were observational studies. The median age of study participants was under 60 years, and only 10 of the 36 studies indicated they were blinded. Surrogate outcomes were utilized in 20 of the studies, employing biomarkers as proxies for clinical endpoints. While surrogate outcomes are commonly accepted in studies for conditions like HIV/AIDS, their correlation with survival rates in oncology studies—accounting for over half of the trials—remains uncertain.

Concerns Raised by Dr. Lexchin

Inclusion of Observational Studies

While Health Canada maintains more stringent methodology requirements than the FDA or EMA, Dr. Lexchin expressed concerns regarding the inclusion of observational studies in the drug approval process aimed at assessing efficacy. Notably, two-thirds of the studies lacked blinding statements, raising the potential for bias, as researchers aware of group assignments may inadvertently influence trial outcomes.

Implications for Drug Approval Interpretation

Interpreting how these results influence the overall drug approval process is complex, as only NOC/c drugs with confirmed publications were included in this analysis. Furthermore, it is crucial to consider any additional trial information shared solely between trial sponsors and Health Canada, especially given the confidentiality of reviewer reports. Future developments may enhance transparency, as Health Canada is actively working on programs to publicly disclose clinical efficacy and safety data related to drug reviews. Dr. Lexchin hopes that making this information accessible will help address concerns regarding the quality of trials approved by Health Canada.

Conclusion

The analysis of clinical trial data and its implications for drug approval processes indicates a need for improved transparency and understanding. As Health Canada continues to develop initiatives aimed at releasing more trial information, it is hoped that these changes will clarify the quality of evidence considered in drug approvals.

References

Lexchin J. Quality of evidence considered by Health Canada in granting full market authorisation to new drugs with a conditional approval: a retrospective cohort study BMJ Open 2018. doi: 10.1136/bmjopen-2017-020377