Bias in spontaneous reporting of adverse drug reactions in Japan.
BACKGROUND
Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan's unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.


METHODS
A manufacturer's database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.


RESULTS
For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.


CONCLUSIONS
Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Shinichi
S
Matsuda
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Kotonari
K
Aoki
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Takuya
T
Kawamata
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Tetsuji
T
Kimotsuki
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Takumi
T
Kobayashi
Clinical Development Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Hiroshi
H
Kuriki
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Terumi
T
Nakayama
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Seigo
S
Okugawa
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Yoshihiko
Y
Sugimura
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Minami
M
Tomita
Drug Safety Division, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Yoichiro
Y
Takahashi
D016907:Adverse Drug Reaction Reporting Systems; D015982:Bias; D006801:Humans; D007564:Japan; D004364:Pharmaceutical Preparations; D060735:Pharmacovigilance; D011358:Product Surveillance, Postmarketing; D013997:Time Factors
D004364:Pharmaceutical Preparations