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Original Investigation |

Effect of Regulatory Requirement for Patient-Specific Prescriptions for Off-Label Medications on the Use of Intravitreal Bevacizumab

Steven Holfinger, MD1; Alexander G. Miller2; Llewelyn J. Rao, MD2; Douglas Y. Rowland, PhD3,4; Joan H. Hornik, AB2; David G. Miller, MD2
[+] Author Affiliations
1Riverside Methodist Hospital, Columbus, Ohio
2Retina Associates of Cleveland, Cleveland, Ohio
3DY Rowland Associates, Cleveland Heights, Ohio
4Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio
JAMA Ophthalmol. 2016;134(1):45-48. doi:10.1001/jamaophthalmol.2015.4331.
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Importance  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.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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 and Relevance  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.

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Relative Percentages of Drug Use

Relative percentages of intravitreal drug use, May 1 to July 30, 2012 (year 1), vs May 1 to July 30, 2013 (year 2), demonstrated a decrease in bevacizumab use and an increase in the use of other drugs. Ranibizumab in 0.3-mg injections was not approved in year 1; therefore, no use is shown in that year. Error bars indicate 95% CIs.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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