Approving molecularly targeted drugs: different approval processes for cytotoxic agents.
BACKGROUND
Recently, the approval of some molecularly targeted drugs has been questioned, due to differing opinions on their risks and benefits. The approval process remains a challenge in regulatory science.


METHODS
We analyzed the molecularly targeted drugs listed in the 2013 Medical Formulary. For the 21 identified drugs, 32 published Pharmaceuticals and Medical Devices Agency (PMDA) reports were open to the public. Data regarding clinical trials were extracted from these reports and assessed in order to clarify the characteristic examinations required for the approval of molecularly targeted drugs.


RESULTS
There was no correlation between the application year and the time between application and approval (p = 0.139). The median number of clinical trials in these reports was 5 (range 1-22). Phase III studies were not included in the assessment materials for 11 reports. A survival benefit was demonstrated for six of the 32 drugs. The PMDA issued approval terms, including all-case surveillance and additional clinical trials, for 24 of these 32 drugs.


CONCLUSIONS
Molecularly targeted drugs were approved by the PMDA using a flexible process based on drug safety and efficacy. Doctors and patients who are administering or receiving these drugs should be fully informed about the lack of Japanese data assessment during these approval processes.
Department of Medical Oncology, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, Yamagata, Japan. itou-ygt@umin.ac.jp.
Yuriko
Y
Sasahara
Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.|Department of Public Health, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Hiroto
H
Narimatsu
Department of Public Health, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Akira
A
Fukao
Department of Clinical Oncology, Yamagata University, Yamagata, Japan.
Takashi
T
Yoshioka
D000970:Antineoplastic Agents / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003603:Cytotoxins; D017277:Drug Approval; D006801:Humans; D007564:Japan; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*; D010602:Pharmacopoeias as Topic; D013997:Time Factors
D000970:Antineoplastic Agents; D003603:Cytotoxins
Approval; Clinical trial; Molecularly targeted drug; PMDA