title: Characteristics of safety information obtained from postmarketing observational studies for re-examination in Japan.
abstract: BACKGROUND
  In Japan, postmarketing surveillance (PMS) studies are required for newly approved drug products to further collect safety information in clinical settings. "PMS study" is a general term encompassing both postmarketing observational (PMO) studies and postmarketing intervention studies for re-examination. Each PMS study is conducted under contracts between the pharmaceutical company and medical institutions in accordance with Good Postmarketing Study Practice. It has been reported that the safety information collected postmarketing is limited because of underreporting. The objective of this investigation was to identify differences among profiles of the drug product safety information collected through intervention studies and observational studies before and after approval. Our study addressed whether the issue of underreporting, generally considered as associated with observational studies, occurs in PMO studies for re-examination. In addition, we considered potential causes of such underreporting.
  
  
  RESULTS
  The overall adverse reaction rate was lower in PMO studies than in intervention studies before approval in almost all cases. The adverse reaction rate in intervention studies exhibited similar profiles regardless of whether they were conducted prior to or following approval. In addition, we found that one reason for a lower adverse reaction rate in PMO studies was that the number of reports of adverse reactions that had occurred frequently prior to approval decreased postmarketing.
  
  
  CONCLUSIONS
  Underreporting was observed even in PMO studies for re-examination under the Japanese regulation. Although it was suggested that expected and common adverse reactions were more likely to be subject to underreporting, further investigation is warranted to explore the reasons for the under-reporting in PMO studies.
authors.affiliation: Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641 Japan ; Department of Research, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641 Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Narukawa
keywords: Package insert; Pharmacovigilance; Postmarketing surveillance; Re-examination; Safety