title: Effect of Regulatory Requirement for Patient-Specific Prescriptions for Off-Label Medications on the Use of Intravitreal Bevacizumab.
abstract: OBJECTIVE
  Requirements regulating pharmaceutical prescriptions can affect physicians' choice of therapy in a clinical setting.
  
  
  OBJECTIVE
  To evaluate the change in bevacizumab use after the regulatory requirement for patient-specific prescriptions (PSPs) for off-label medications in Ohio.
  
  
  METHODS
  This study retrospectively reviewed the aggregate data from the billing records of patients receiving 1.25-mg injections of bevacizumab, 0.3- or 0.5-mg injections of ranibizumab, or 2.0-mg injections of aflibercept for age-related macular degeneration or diabetic macular edema in a 9-member retinal specialty private practice. The review assessed 4488 intravitreal injections in the 3-month period before (May 1 to July 30, 2012) and 5253 injections in the 3-month period after (May 1 to July 30, 2013) the Ohio Board of Pharmacy's requirement of PSPs for bevacizumab. Relative proportions of the drugs used for intravitreal injections were calculated and frequencies were compared. A Likert scale survey was conducted among the 9 physicians to identify reasons for their change in prescription of bevacizumab. The survey inquired about (1) the burden of PSPs, (2) concern about differences in efficacy, and (3) concern about differences in safety.
  
  
  METHODS
  Difference in drug use before and after the PSP requirement for bevacizumab and the physicians' reasons for change in their drug use.
  
  
  RESULTS
  Bevacizumab use decreased from 2752 of 4488 pre-PSP injections (61.3%) to 1503 of 5253 post-PSP injections (28.6%), a change of -32.7% (95% CI, -34.6% to -30.8%; P < .001). Use of 0.5-mg ranibizumab injections increased from 1122 of 4488 pre-PSP injections (25.0%) to 1838 of 5253 post-PSP injections (35.0%), a change of 10.0% (95% CI, 8.2% to 11.8%; P < .001). Use of 0.3-mg ranibizumab injections increased from 0 of 4488 (before US Food and Drug Administration approval) to 429 of 5253 post-PSP injections (8.2%), a change of 8.2% (95% CI, 7.4% to 8.9%; P < .001). Use of aflibercept injections increased from 614 of 4488 pre-PSP injections (13.7%) to 1483 of 5253 post-PSP injections (28.2%), a change of 14.6% (95% CI, 13.0%-16.1%; P < .001). In the survey of the 9 physicians concerning their reasons for decreased use of bevacizumab, 7 (78%) strongly agreed and 1 (11%) agreed that the burden of PSPs changed their choice of drug used for injection.
  
  
  CONCLUSIONS
  Use of bevacizumab was reduced by 32.7% 1 year after the regulatory requirement for PSPs for compounded (repackaged) medications. This change seemed to have more association with the requirement for PSPs than with a known change in efficacy or safety concerns. Although this study was based on a single US practice, regulation of repackaged medication for safety concerns should also consider the evaluation of treatment burden, cost, and adherence.
authors.affiliation: Riverside Methodist Hospital, Columbus, Ohio.
authors.forename: Steven
authors.initials: S
authors.lastname: Holfinger
authors.affiliation: Retina Associates of Cleveland, Cleveland, Ohio.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Miller
authors.affiliation: Retina Associates of Cleveland, Cleveland, Ohio.
authors.forename: Llewelyn J
authors.initials: LJ
authors.lastname: Rao
authors.affiliation: DY Rowland Associates, Cleveland Heights, Ohio4Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Douglas Y
authors.initials: DY
authors.lastname: Rowland
authors.affiliation: Retina Associates of Cleveland, Cleveland, Ohio.
authors.forename: Joan H
authors.initials: JH
authors.lastname: Hornik
authors.affiliation: Retina Associates of Cleveland, Cleveland, Ohio.
authors.forename: David G
authors.initials: DG
authors.lastname: Miller
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D004339:Drug Compounding; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D004363:Drug Utilization / Q000706:statistics & numerical data*; D006801:Humans; D058449:Intravitreal Injections; D007880:Legislation, Drug; D056687:Off-Label Use / Q000331:legislation & jurisprudence*; D009820:Ohio; D018802:Patient-Centered Care; D010818:Practice Patterns, Physicians'; D012164:Retinal Diseases / Q000188:drug therapy; D012189:Retrospective Studies; D014481:United States; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab