Mori Jinichi, Tanimoto Tetsuya, Miura Yuji, Kami Masahiro
Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo Division of Internal Medicine, Jyoban Hospital, Tokiwakai
Division of Internal Medicine, Jyoban Hospital, Tokiwakai Division of Social Communication System for Advanced Clinical Research, Institute of Medical Science, The University of Tokyo, Tokyo.
Jpn J Clin Oncol. 2015 Jun;45(6):588-94. doi: 10.1093/jjco/hyv030. Epub 2015 Mar 10.
All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry.
We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action.
Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance.
All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions.
在日本，通常会对所有患者开展新批准抗癌药物的全病例上市后监测。本研究调查全病例上市后监测能否识别出药物上市前未被发现的致命药物不良反应。
我们通过查阅公开的上市后监测结果，检查经由全病例上市后监测识别出的致命药物不良反应，并通过查阅药品标签确定首次报告致命药物不良反应的时间点。我们还浏览了日本监管机构网站上的紧急警报，以评估全病例上市后监测与监管行动之间的关系。
1999年1月至2009年12月期间共进行了25次全病例上市后监测。8次有最终结果的全病例上市后监测包含了所有致命病例的信息。其中，患者中位数为1287例（范围：106 - 4998例），致命药物不良反应中位数为14.5例（范围：4 - 23例）。在这8次上市后监测中检测到的111例致命药物不良反应中，最初的全球药品标签和最初的日本药品标签上分别仅描述了28例（25.0%）和22例（19.6%），58例（52.3%）致命药物不良反应首次在全病例上市后监测报告中被描述。尽管如此，监管机构仅发出了4封警告信，其中2封是由全病例上市后监测的病例报告引发的。
日本对新批准抗癌药物进行的全病例上市后监测有助于严格汇总非特异性药物不良反应，但很少能检测到具有临床意义的致命药物不良反应。
