title: Utilisation of human pharmacology studies with biomarkers for new drug applications in Japan.
abstract: OBJECTIVE
  This study evaluated the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation conducted for new drug applications (NDAs) submitted to the Japanese regulatory authority, the Ministry of Health, Labour and Welfare (MHLW).
  
  
  METHODS
  A total of 50 new chemical entities (NCEs) posted on the Websites, which were approved from June 2000 to November 2001, were evaluated by investigating their approval information. The utilisation of human pharmacology studies with biomarkers was evaluated by focusing on the classification referred to biomarkers for either efficacy or safety estimation and timing of studies.
  
  
  RESULTS
  The human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted in 20 compounds classified by utilising measures of either efficacy (17 compounds) or safety (seven compounds). In 4 of 17 NCEs, some of the biomarkers in human pharmacology studies were similar to the clinical endpoints for efficacy assessment in therapeutic exploratory and/or therapeutic confirmatory studies. For safety assessment in therapeutic exploratory and/or therapeutic confirmatory studies, clinical endpoints rather than biomarkers in human pharmacology studies were used in all seven NCEs. The timing of each type of clinical study could only be obtained for 15 NCEs. Of these 15 NCEs, human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted on six compounds. There were only two compounds for which human pharmacology studies with biomarkers for efficacy estimation were conducted before pivotal studies such as a therapeutic exploratory study or a bridging study.
  
  
  CONCLUSIONS
  Our survey suggests that with Japanese NDAs, human pharmacology studies with biomarkers for either efficacy or safety estimation do not play a key role in accelerating drug development and maximising the knowledge gained from confirmatory trials. The relationship between a biomarker and a clinical endpoint should be investigated appropriately for accelerating drug development. We think that the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation in the regulatory review process for NDAs should be encouraged with the advancements of drug evaluation research using an appropriate biomarker based on clinical pharmacology.
authors.affiliation: Laboratory of Bio-Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan. ykodama@jiu.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kodama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Saito
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ono
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kodama
authors.forename: Masae
authors.initials: M
authors.lastname: Kuranari
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Yaplee
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takano-Ohmuro
authors.forename: Mizue
authors.initials: M
authors.lastname: Mutoh
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007564:Japan
chemical_list: D015415:Biomarkers