Data from: Quality of evidence considered by Health Canada in granting full market authorization to new drugs with a conditional approval: a retrospective cohort study

Objectives: This study examines the characteristics of studies that Health
Canada uses to grant full marketing authorization for products given a
conditional approval between January 1, 1998 and June 30, 2017. Design:
Cohort study. Data sources: Journal articles listing drugs that fulfilled
their conditions and received full marketing authorization, Notice of
Compliance database, Notice of Compliance with conditions web site,
Qualifying Notices listing required confirmatory studies,
clinicaltrials.gov, PubMed, Embase, companies making products being
analyzed, journal articles resulting from confirmatory studies.
Interventions: None Primary and secondary outcome measures:
Characteristics of studies - study design (randomized 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 randomized
controlled trials (RCTs) but only 10 stated if they were blinded. Twenty
used surrogate outcomes. The median age of patients was 56 (interquartile
range (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 number women may make it hard to differentiate responses
by sex. These results raise potential concerns about the quality of
evidence that Health Canada accepts.