Nishimura Tsutomu, Tada Harue, Nakagawa Masatsugu, Teramukai Satoshi, Matsui Shigeyuki, Fukushima Masanori
Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
Pharmacoepidemiology, Graduate School of Public Health, Kyoto University , Kyoto, ( Japan ).
Pharm Pract (Granada). 2006 Oct;4(4):168-78. doi: 10.4321/s1885-642x2006000400004.
The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future.
We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society.
We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed.
We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan.
本研究的目的是识别吉非替尼在审批、药物警戒及审批后监管决策程序中存在的问题，并提出对策，以防止未来在日本出现更多由药物引起的痛苦。
我们全面回顾了2000年至2006年期间监管机构、含吉非替尼药物的制造商、癌症临床研究组及一个科学学会发表的有关吉非替尼的报告。
我们在审批、药物警戒及监管决策程序中识别出以下主要问题：1）动物实验和上市前临床试验的结果，以及其他国家的药物不良反应报告未在药品标签中得到恰当体现；2）在未严格评估上市前临床试验外部有效性的情况下扩大了药物适应症；3）尽管自发报告了许多间质性肺病（ILD）严重病例，但未立即开展精心设计的上市后监测。
我们建议对所有药物使用者进行强制性全面登记及监测（即前瞻性结局研究），作为防止未来在日本出现更多由药物引起的痛苦的合理解决方案之一。
