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. 2015 May 1;10(5):e0126413.
doi: 10.1371/journal.pone.0126413. eCollection 2015.

Bias in spontaneous reporting of adverse drug reactions in Japan

Shinichi Matsuda  1 , Kotonari Aoki  1 , Takuya Kawamata  1 , Tetsuji Kimotsuki  1 , Takumi Kobayashi  1 , Hiroshi Kuriki  2 , Terumi Nakayama  1 , Seigo Okugawa  1 , Yoshihiko Sugimura  1 , Minami Tomita  1 , Yoichiro Takahashi  1
Affiliations

Bias in spontaneous reporting of adverse drug reactions in Japan

Shinichi Matsuda et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: All authors are employees of Chugai Pharmaceutical Co. Ltd. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Adverse drug reaction reporting trend for 5 drugs.
Total number of individual case safety reports for (A) capecitabine, (B) eldecalcitol, (C) epoetin beta pegol, (D) peginterferon alfa-2a, and (E) sevelamer hydrochloride.
Fig 2
Fig 2. The proportion of adverse drug reactions reported to the manufacturer within 2 weeks of onset.
(A) capecitabine, (B) eldecalcitol, (C) epoetin beta pegol, (D) peginterferon alfa-2a, and (E) sevelamer hydrochloride. Error bars represent the 95% confidence intervals.
Fig 3
Fig 3. Serious: Non-serious ratios over time.
(A) capecitabine, (B) eldecalcitol, (C) epoetin beta pegol, (D) peginterferon alfa-2a, and (E) sevelamer hydrochloride.
Fig 4
Fig 4. High prominence:Low prominence ratios over time.
(A) capecitabine, (B) eldecalcitol, (C) epoetin beta pegol, (D) peginterferon alfa-2a, and (E) sevelamer hydrochloride.
Fig 5
Fig 5. High frequency:Low frequency ratios over time.
(A) capecitabine, (B) eldecalcitol, (C) epoetin beta pegol, (D) peginterferon alfa-2a, and (E) sevelamer hydrochloride.
See this image and copyright information in PMC

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