title: Analysis of labeling decisions regarding therapeutic indications during new drug application reviews in Japan.
abstract: We analyzed regulatory reviews in Japan to study the modifications made in drug labeling with respect to proposed therapeutic indications, and investigated factors associated with these changes so as to gain insight into the reasons behind the decisions. Of 220 new molecular entities (NMEs) approved in Japan from 2000 to 2009, 70 received more restricted indications and 14 received more expanded indications than those proposed by the applicants. Multinomial regression analysis suggested that the presence of competitive drugs in the market, higher estimated peak sales, and higher complexity of the proposed indication were factors that significantly increased the likelihood of the indications being restricted on review, in addition to factors related to adequacy of efficacy data. Our results give us a clue to how the approved therapeutic indications reflect the characteristics of the applicants, drugs, review areas (RAs), and clinical evidence in the submitted data package, as well as to the principle behind the decisions.
authors.affiliation: Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Kusama
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: S
authors.initials: S
authors.lastname: Ono
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D015195:Drug Design; D004345:Drug Industry; D004348:Drug Labeling; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007564:Japan; D018570:Risk Assessment
chemical_list: D015507:Drugs, Investigational