title: Adherence to risk evaluation and mitigation strategies (REMS) requirements for monthly testing of liver function.
abstract: BACKGROUND
  Risk evaluation and mitigation strategies (REMS), as mandated by the US Food and Drug Administration (FDA) for medications with the potential for harm, are increasingly incorporating rigid protocols for patient evaluation, but little is known about compliance with these programs. Despite the inherent limitations, data on administrative claims may provide an opportunity to investigate adherence to these programs.
  
  
  METHODS
  We assessed adherence to liver function test (LFT) requirements included in the REMS program for bosentan through use of administrative claims. Patients observed in the Optum Research Database who were initiators of bosentan from November 20, 2001 to March 31, 2013 were included. Adherence to LFTs was calculated using pharmacy claims for bosentan dispensation and medical claims for laboratory services, and was assessed at the time of drug initiation and within specified time intervals throughout follow-up.
  
  
  RESULTS
  Of 742 patients, 523 (70.5%) had ≥1 qualifying LFT. Among patients with ≥12 dispensations, claims for LFTs at individual dispensations were 53.2-64.0%. Median proportion of dispensations with ≥1 LFT was 0.8 among patients with ≥6 (interquartile range, 0.7-1.0) or ≥12 (0.7-0.9) dispensations. Adherence was 90-100% for 33.3% of all initiators, whereas 29.3% of initiators were non-adherent (defined as <50% of on-therapy LFTs).
  
  
  CONCLUSIONS
  Analyses of administrative claims suggest that the REMS program for bosentan may not have adequately guaranteed adherence to the program's monthly monitoring of LFTs. Such investigations of existing REMS programs may provide insight on how to accomplish more successful evaluation of REMS.
authors.affiliation: University of North Carolina, Charlotte, NC, USA;
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Blanchette
authors.affiliation: Optum Epidemiology, Waltham, MA, USA;
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Nunes
authors.affiliation: Optum Epidemiology, Waltham, MA, USA;
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Lin
authors.affiliation: Optum Epidemiology, Waltham, MA, USA;
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mortimer
authors.affiliation: University of North Carolina, Charlotte, NC, USA;
authors.forename: Joshua
authors.initials: J
authors.lastname: Noone
authors.affiliation: Otsuka America Pharmaceutical, Inc., Princeton, NJ, USA;
authors.forename: Krishna
authors.initials: K
authors.lastname: Tangirala
authors.affiliation: Truven Health Analytics, Washington, DC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
authors.affiliation: Otsuka America Pharmaceutical, Inc., Princeton, NJ, USA;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gutierrez
keywords: FDA; REMS; adherence; administrative claims; compliance; liver function test; patient assessment; risk evaluation