title: Approval gap of pharmacogenomic biomarkers and in vitro companion diagnostics between the United States and Japan.
abstract: OBJECTIVE
  In vitro companion diagnostic devices (CDx) provide information on pharmacogenomic biomarkers (PGBMs) to enable the safe and effective use of targeted agents for personalized therapy. These devices require specific regulations that strike a balance between scientific evidence and financial burden. The aims were to compare approval of PGBMs and CDx in the USA and Japan and to help inform current discussions on personalized medicine.
  
  
  METHODS
  We analysed published documentation from the USA and Japan for CDx and PGBMs, listed by the US Food and Drug Administration (FDA). Aspects evaluated were aim, approval state and therapeutic area. Coverage by the National Health Insurance in Japan was also investigated.
  
  
  CONCLUSIONS
  Thirty-eight PGBMs were listed in the FDA table as of March 2013. In the USA, the aim was efficacy in 55% (21/38). The largest therapeutic area was oncology (39%, 15/38). Fifty-three per cent (20/38) of the PGBMs had a corresponding CDx approved. Of the 38 PGBMs in the FDA table, six had no approved drug in Japan; in 16 of the remaining 32 PGBMs, the aim was efficacy. The largest therapeutic area was oncology (34%, 11/32). Of the 32 PGBMs, 15 were associated with an approved and/or covered CDx, with only 11 having an approved CDx. Four PGBMs had a covered CDx without prior approval in Japan.
  
  
  CONCLUSIONS
  Our study confirms that there is still a substantial gap in the approval of PGBMs and CDx between Japan and the USA. Complementary coverage of unapproved CDx by the National Health Insurance, however, is raising access to a similar level in both countries. Because the number of expensive personalized medicines and CDx is increasing, patient access will continue to be an important challenge to healthcare systems in all countries.
authors.affiliation: Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Shimazawa
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003430:Cross-Sectional Studies; D057069:Diagnostic Test Approval / Q000331:legislation & jurisprudence*; D003955:Diagnostic Tests, Routine; D006297:Health Services Accessibility; D006801:Humans; D007564:Japan; D010597:Pharmacogenetics; D057285:Precision Medicine / Q000379:methods; D014481:United States
chemical_list: D015415:Biomarkers
keywords: USFDA; biomarkers; drug approval; in vitro diagnostic devices; personalized medicine; pharmacogenomics