PMID- 30187590
OWN - NLM
STAT- MEDLINE
DCOM- 20190923
LR  - 20190923
IS  - 1099-1557 (Electronic)
IS  - 1053-8569 (Linking)
VI  - 27
IP  - 11
DP  - 2018 Nov
TI  - Factors distinguishing important identified risks from important potential risks 
      in orphan and nonorphan drugs: An analysis of safety specifications of Japan and 
      European Union risk management plans.
PG  - 1231-1238
LID - 10.1002/pds.4646 [doi]
AB  - PURPOSE: The purposes of the study are to compare safety specifications between 
      Japan and the European Union (EU) and to identify the factors affecting 
      categorization of important identified or potential risks. METHODS: Safety 
      specifications were collected from orphan and nonorphan drugs approved in Japan 
      between 2014 and 2016, and in the EU as of October 2017. Outcome was defined 
      dichotomously as listed as important identified risks or potential risks. A 
      mixed-effects logistic regression was performed to estimate odds ratios of being 
      listed as important identified risks. RESULTS: This study included 20 orphan and 
      33 nonorphan drugs. The number of safety specifications per drug and the 
      distribution of risk categories were significantly different between Japan and 
      the EU regardless of orphan status. In orphan drugs, the occurrence of serious 
      adverse events (AEs) during clinical trials for new drug applications was 
      associated with a higher probability of being listed as important identified 
      risks in Japan, while AE rate (%) was positively associated with being listed as 
      important identified risks in the EU. For nonorphan drugs in Japan, AE occurring 
      at a high rate, adverse drug reactions (ADRs) listed as important identified 
      risks in EU risk management plans, and clinically significant ADRs known in 
      similar drugs were likely to be listed as important identified risks, whereas a 
      >/=1.4 risk ratio was associated with a higher probability of being listed as 
      important identified risks in the EU. CONCLUSIONS: Factors affecting risk 
      categories were different between Japan and the EU, which might contribute to the 
      difference in safety specifications between these 2 regions.
CI  - (c) 2018 John Wiley & Sons, Ltd.
FAU - Hirota, Saeko
AU  - Hirota S
AUID- ORCID: 0000-0003-0266-118X
AD  - Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Yamaguchi, Takuhiro
AU  - Yamaguchi T
AD  - Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180905
PL  - England
TA  - Pharmacoepidemiol Drug Saf
JT  - Pharmacoepidemiology and drug safety
JID - 9208369
SB  - IM
MH  - Adverse Drug Reaction Reporting Systems/statistics & numerical data
MH  - Drug Labeling/legislation & jurisprudence/*standards
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/etiology/*prevention 
      & control
MH  - European Union/*organization & administration
MH  - Humans
MH  - Japan
MH  - Orphan Drug Production/*legislation & jurisprudence
MH  - Risk Assessment/methods
MH  - Risk Management/legislation & jurisprudence/*methods
OTO - NOTNLM
OT  - pharmacoepidemiology
OT  - pharmacovigilance
OT  - rare diseases
OT  - risk management plan
OT  - safety specification
EDAT- 2018/09/07 06:00
MHDA- 2019/09/24 06:00
CRDT- 2018/09/07 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/07/26 00:00 [revised]
PHST- 2018/08/07 00:00 [accepted]
PHST- 2018/09/07 06:00 [pubmed]
PHST- 2019/09/24 06:00 [medline]
PHST- 2018/09/07 06:00 [entrez]
AID - 10.1002/pds.4646 [doi]
PST - ppublish
SO  - Pharmacoepidemiol Drug Saf. 2018 Nov;27(11):1231-1238. doi: 10.1002/pds.4646. 
      Epub 2018 Sep 5.