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Quality of evidence considered by Health Canada in granting full market authorisation to new drugs with a conditional approval: a retrospective cohort study
    1. 1 School of Health Policy and Management, York University, Toronto, Ontario, Canada
    2. 2 Emergency Department, University Health Network, Toronto, Ontario, Canada
    1. Correspondence to Dr Joel Lexchin; jlexchin{at}yorku.ca

    Abstract

    Objectives This study examines the characteristics of studies that Health Canada uses to grant full marketing authorisation for products given a conditional approval between 1 January 1998 and 30 June 2017.

    Design Cohort study.

    Data sources Journal articles listing drugs that fulfilled their conditions and received full marketing authorisation, Notice of Compliance database, Notice of Compliance with conditions website, Qualifying Notices listing required confirmatory studies, clinicaltrials.gov, PubMed, Embase, companies making products being analysed, journal articles resulting from confirmatory studies.

    Interventions None.

    Primary and secondary outcome measures Characteristics of studies—study design (randomised controlled trials, observational), primary outcome used (clinical, surrogate), blinding, number of patients in studies, patient median age, number of men and women.

    Results Eleven companies confirmed 36 publications for 19 products (21 indications). Twenty-nine out of the 36 studies were randomised controlled trials (RCTs) but only 10 stated if they were blinded. Twenty used surrogate outcomes. The median age of patients was 56 (IQR 44–61). The median number of men per study/trial was 184 (IQR 58–514) versus women 141 (IQR 46–263).

    Conclusions Postmarket studies required by Health Canada had more rigorous methodology than those required by either the Food and Drug Administration or the European Medicines Agency. There were still deficiencies in these studies. The absence of blinding in the majority of RCTs may introduce bias in their results. The use of surrogate outcomes especially in oncology trials means that improvements in survival are not available. The relatively young age of patients, even for products for cancer, means that predicting how the elderly will respond is often unknown. The almost universal finding that men outnumbered women may make it hard to differentiate responses by sex. These results raise potential concerns about the quality of evidence that Health Canada accepts.

    • health policy
    • clinical trials
    • confirmatory studies, health canada, methodology, postmarket, regulation

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Contributors JL came up with the idea for this study, gathered and analysed the data and wrote the manuscript.

    • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests In 2015-2017, JL received payment from two non-profit organisations for being a consultant on a project looking at indication-based prescribing and a second looking at which drugs should be distributed free of charge by general practitioners. In 2015, he received payment from a for-profit organisation for being on a panel that discussed expanding drug insurance in Canada. He is on the Foundation Board of Health Action International.

    • Patient consent Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Extra data can be accessed via the Dryad data repository at DOI: doi:10.5061/dryad.82jv0.

    • Collaborators Catherine Oliver.

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