Data from: Postmarket safety in Canada: are significant therapeutic advances and biologics less safe than other drugs? A cohort study

Objectives: Examine the probability of new active substances (NASs) approved in Canada between 1 January 1997 and 31 March 2012 acquiring a serious postmarket safety warning. Design: Cohort study. Data sources: Annual reports of the Therapeutic Products Directorate and the Biologic and Genetic Therapies Directorate; evaluations of therapeutic innovation from the Patented Medicine Prices Review Board and Prescrire International; MedEffect Canada website. Interventions: Postmarket regulatory safety warning or withdrawal from market due to safety reasons. Primary and secondary outcome measures: Compare the probability of acquiring a postmarket safety warning in Canada in four different groups of drugs: (1) traditional medications versus biologics; (2) medications that offer significant new therapeutic benefits versus those that do not. Determine how well the type of review that an NAS received from Health Canada predicted the product's postmarket therapeutic value. Results: The probability of a traditional NAS acquiring a serious safety warning and/or being withdrawn was 29.9% (95% CI 21.8% to 40.2%) vs 27.3% (95% CI 18.2% to 39.7%) for an NAS of biological origin (p=0.47, log-rank test). For medications that were significant therapeutic advances the probability was 40.2% (95% CI 24.5% to 60.9%) vs 33.9% (95% CI 26.4% to 42.7%) for those that were not (p=0.18, log-rank test). Health Canada was 77.4% accurate in predicting the therapeutic importance of an NAS. Conclusions: There was no difference in postmarket regulatory safety action between traditional medications and biologics and no difference between drugs with significant therapeutic benefits and those without. Although these results draw on Canadian data, they are likely to be relevant internationally. Further research should assess whether the current level of premarket safety evaluation is acceptable.

研究目标：探究1997年1月1日至2012年3月31日期间在加拿大获批的新活性物质（New Active Substances, NAS）出现严重上市后安全警示的概率。
研究设计：队列研究。
数据来源：治疗产品局（Therapeutic Products Directorate）与生物及基因治疗局（Biologic and Genetic Therapies Directorate）的年度报告、专利药品价格审查委员会（Patented Medicine Prices Review Board）的治疗创新评估内容、国际《Prescrire》期刊资料，以及加拿大MedEffect官方网站。
干预措施：因安全原因被施加上市后监管安全警示或从市场撤出。
主要与次要结局指标：对比四类药物在加拿大获得上市后安全警示的概率：(1) 传统药物与生物制剂；(2) 具备显著新治疗获益的药物与不具备该获益的药物；同时评估加拿大卫生部（Health Canada）对新活性物质所采用的审评类型能否有效预测该产品的上市后治疗价值。
结果：传统新活性物质出现严重安全警示和/或被撤市的概率为29.9%（95%置信区间21.8%~40.2%），生物来源新活性物质的对应概率为27.3%（95%置信区间18.2%~39.7%）（log-rank检验，p=0.47）。对于具备显著治疗进展的药物，其出现上述情况的概率为40.2%（95%置信区间24.5%~60.9%），而不具备该进展的药物为33.9%（95%置信区间26.4%~42.7%）（log-rank检验，p=0.18）。加拿大卫生部对新活性物质治疗重要性的预测准确率达77.4%。
结论：传统药物与生物制剂在上市后监管安全处置方面无显著差异，具备显著治疗获益的药物与不具备该获益的药物亦无此类差异。尽管本研究结果基于加拿大数据，但可能对国际场景具有参考价值。未来应开展进一步研究，评估当前上市前安全审评的水平是否可接受。