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.

研究目的：本研究旨在分析加拿大卫生部（Health Canada）于1998年1月1日至2017年6月30日期间，对已获得条件性批准的产品授予完全上市许可所依据的研究特征。
研究设计：队列研究（Cohort study）。
数据来源：收录满足条件并获得完全上市许可的药品的期刊文献、合规通知书（Notice of Compliance）数据库、带条件的合规通知书官方网站、列明所需验证性研究的合格通知书、临床试验注册平台（clinicaltrials.gov）、PubMed、Embase、拟分析产品的生产企业，以及验证性研究产出的期刊文献。
干预措施：无。
主要与次要结局指标：研究特征——研究设计（随机对照试验（randomized controlled trial, RCT）、观察性研究）、所采用的主要结局类型（临床结局、替代结局）、设盲情况、研究纳入的患者数量、患者中位年龄、男性与女性患者数量。
研究结果：11家企业为19款产品（21个适应症）确认了36篇相关文献。36项研究中，29项为随机对照试验，但仅10项明确提及是否采用设盲设计。20项研究使用了替代结局。患者的中位年龄为56岁（四分位距（interquartile range, IQR）：44~61）。单项研究/试验中男性患者的中位数为184例（IQR：58~514），女性患者中位数为141例（IQR：46~263）。
研究结论：加拿大卫生部要求的上市后研究，其方法学严谨性高于美国食品药品监督管理局（Food and Drug Administration, FDA）与欧洲药品管理局（European Medicines Agency, EMA）所要求的同类研究，但此类研究仍存在不足。多数随机对照试验未采用设盲设计，可能会对研究结果引入偏倚。尤其是肿瘤学试验中大量使用替代结局，意味着无法直接获取患者生存改善相关数据。即便针对癌症治疗产品，受试患者仍相对年轻，这使得临床医师往往难以预测老年人群的用药响应。几乎所有研究均显示男性患者数量多于女性，这可能会增加按性别区分用药响应的分析难度。上述研究结果对加拿大卫生部所采信的证据质量提出了潜在担忧。