Main Article Content
Off-label drug use, drug reimbursement, drug coverage, Ontario
Background: A Canadian Agency for Drugs and Technologies in Health (CADTH) therapeutic review concluded that bevacizumab and ranibizumab have similar efficacy and safety in treating retinal conditions and recommended bevacizumab be used as preferred initial therapy based on a cost-saving perspective. Such use would be off-label because bevacizumab is not approved for these conditions and has a serious safety warning (SSW) in its Product Monograph (PM) about intravitreal use.
Objective: To evaluate whether the Ontario Public Drug Programs (OPDP) reimbursement is provided only for off-label use for serious, life-threatening or severely debilitating conditions and not when the drug’s PM contains a SSW against such use.
Methods: OPDP reimbursement criteria for non-palliative drugs from its frequently-requested Exceptional Access Program (EAP) and Limited Use (LU) lists were compared with approved indications and SSWs in the drugs’ PMs.
Results: Of 125 unique frequently-requested non-palliative EAP drugs, 12 included off-label use for serious conditions for which no alternative treatment exists. Eight of the 12 had SSWs, but only one warning for orally-administered sirolimus related directly to the OPDP-reimbursed off-label use. Of 29 injectable non-palliative LU drugs, one had off-label LU criteria allowing reimbursement for an unapproved indication and a SSW unrelated to the reimbursable indication.
Conclusion: Presently, OPDP only reimburse drugs for off-label use for the treatment of serious, life-threatening or severely debilitating conditions for which no alternative treatment exists. OPDP should not diverge from this approach by allowing cost-savings to trump appropriate drug use, which would set a unique and unprecedented example.
2. Anti-vascular endothelial growth factor (VEGF) drugs for the treatment of retinal conditions: recommendations report. [Internet] CADTH; 2016. Available at: https://www.cadth.ca/sites/default/files/pdf/TR0009_Anti-VEGFs_Recs_Report.pdf
3. Hoffman La Roche Ltd. Avastin Product Monograph [Internet] 2018. https://pdf.hres.ca/dpd_pm/00045825.PDF.
4. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol 2010;128:1273–9.
5. Gower EW, Cassard C, Chu L, Varma R, Klein R. Adverse events following intravitreal injection of Avastin or Lucentis for treating age-related macular degeneration (abstract 6644). Association for Research in Vision and Ophthalmology Annual Meeting; May 2011.
6. CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364:1897–908.
7. Novartis Pharmaceuticals. Lucentis Product Monograph. 2017. [Internet]. Available at: https://pdf.hres.ca/dpd_pm/00042080.PDF.
8. Bayer Inc. Eylea Product Monograph. 2018. [Internet] https://pdf.hres.ca/dpd_pm/00046211.PDF
9. Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc 2012;87:982–90.
10. Carton L, Cottencin O, Lapeyre-Mestre M, et al. Off-label prescribing of antipsychotics in adults, children and elderly individuals: a systematic review of recent prescription trends. Curr Pharm Des 2015;21:3280–97.
11. Saiyed MM, Ong PS, Chew L. Off-label drug use in oncology: a systematic review of literature. J Clin Pharm Ther 2017;42:251–8.
12. Culshaw J, Kendall D, Wilcock A. Off-label prescribing in palliative acre: a survey of independent prescribers. Palliat Care 2013;27:314–9.
13. Choonara I, Conroy S. Unlicensed and off-label drug use in children: implications for safety. Drug Saf 2002;25:1–5.
14. Eguale T, Buckeridge DL, Verma A, et al. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med 2016;176:55–63.
15. Government of Ontario. Get coverage for prescription drugs [Internet]. 2018. Available at: https://www.ontario.ca/page/get-coverage-prescription-drugs
16. Government of Ontario. Formulary search [Internet] 2016. Available at: https://www.formulary.health.gov.on.ca/formulary.
17. Government of Ontario. Exceptional Access Program (EAP) reimbursement criteria [Internet] 2018. Available at: http://www.health.gov.on.ca/en/pro/programs/drugs/eap_criteria.aspx
18. Rawson NSB. What does the new Ontario pharmacare plan offer children and young adults with rare disorders? J Popul Ther Clin Pharmacol 2017;24:90–8.
19. Government of Ontario. EAP reimbursement criteria for frequently requested drugs [Internet] 2017. Available at: http://www.health.gov.on.ca/en/pro/programs/drugs/pdf/frequently_requested_drugs.pdf.
20. Government of Ontario. Telephone request service reimbursement criteria Exceptional Access Program [Internet] 2015. Available at: http://www.health.gov.on.ca/en/public/programs/drugs/publications/trs/trs_guide.pdf.
21. Health Canada. Drug product database online query [Internet] 2018. Available at: https://health-products.canada.ca/dpd-bdpp/index-eng.jsp.