J Korean Med Assoc.  2018 Mar;61(3):140-146. 10.5124/jkma.2018.61.3.140.

Appropriate off-label drug use

  • 1Health Insurance Review and Assessment Service, Seoul, Korea. lsmlight@hira.or.kr


After new drugs are introduced into an area of medical practice through the regulatory approval process, clinicians gain further experience using the drugs and amass real-world evidence regarding their efficacy. For these reasons, drugs can be prescribed in contexts extending beyond their labeled indication, dosage, or route because of unmet needs or additional benefits, such as cost-effectiveness. Off-label drug use (OLDU) is widespread in various clinical fields, especially in pediatrics, obstetrics, psychiatry, and oncology; however, the small amount of supporting evidence associated with increased adverse drug events has emerged as an important issue regarding OLDU. Nonetheless, OLDU has officially been allowed in South Korea by an announcement of the Ministry of Health and Welfare, a public announcement of the Health Insurance Review and Assessment Service for cancer drugs, and through submissions to the Health Insurance Review and Assessment Service by hospitals after receiving institutional review board approval. Despite these systems, the proper scope of OLDU has been a topic of debate. In order to improve the appropriateness of OLDU, a transparent system for evidence-based recommendations, conditional decision-making, and monitoring of adverse drug events should be established and organized in collaboration with existing systems to promote consistent decision-making.


Off-label use; Drug-related side effects and adverse reactions; Evidence-based medicine; Patient safety

MeSH Terms

Cooperative Behavior
Drug-Related Side Effects and Adverse Reactions
Ethics Committees, Research
Evidence-Based Medicine
Insurance, Health
Off-Label Use
Patient Safety


1. Park BJ. Policy for drug safety and its impact on the patient safety. J Korean Med Assoc. 2012; 55:816–818.
2. Kohn LT, Corrigan J, Donaldson MS. To err is human: building a safer health system. Washington, DC: National Academy Press;2000.
3. Sutherland A, Waldek S. It is time to review how unlicensed medicines are used. Eur J Clin Pharmacol. 2015; 71:1029–1035.
4. Wittich CM, Burkle CM, Lanier WL. Ten common questions (and their answers) about off-label drug use. Mayo Clin Proc. 2012; 87:982–990.
5. Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C Jr, Hyman D, Jenkins K, White ML, Levy FH, Levin JE, Bertoch D, Slonim AD. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007; 161:282–290.
6. Lenk C, Duttge G. Ethical and legal framework and regulation for off-label use: European perspective. Ther Clin Risk Manag. 2014; 10:537–546.
7. Herring C, McManus A, Weeks A. Off-label prescribing during pregnancy in the UK: an analysis of 18,000 prescriptions in Liverpool Women's Hospital. Int J Pharm Pract. 2010; 18:226–229.
8. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006; 166:1021–1026.
9. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2005; 36:331–335.
10. American Academy of Ophthalmology Retina/Vitreous PPP Panel. Age-related macular degeneration PPP: updated 2015 [Internet]. 2015. cited 2017 Dec 15. Available from: https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015.
11. Leung LS, Zarbin MA, Rosenfeld PJ, Toy B, Martin DF, Blumenkranz MS. Pharmacotherapy of age-related macular degeneration. In : Schachat AP, Sadda SR, Hinton DR, Wilkinson CP, Weidemann P, editors. Ryan's retina. 6th ed. Edinburgh: Elsevier;2018. p. 1373–1422.
12. Saiyed MM, Ong PS, Chew L. Off-label drug use in oncology: a systematic review of literature. J Clin Pharm Ther. 2017; 42:251–258.
13. Mellor JD, Van Koeverden P, Yip SW, Thakerar A, Kirsa SW, Michael M. Access to anticancer drugs: many evidence-based treatments are off-label and unfunded by the Pharmaceutical Benefits Scheme. Intern Med J. 2012; 42:1224–1229.
14. Chen DT, Wynia MK, Moloney RM, Alexander GC. US physician knowledge of the FDA-approved indications and evidence base for commonly prescribed drugs: results of a national survey. Pharmacoepidemiol Drug Saf. 2009; 18:1094–1100.
15. Eguale T, Buckeridge DL, Verma A, Winslade NE, Benedetti A, Hanley JA, Tamblyn R. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med. 2016; 176:55–63.
16. Recent developments in medicare coverage of off-label cancer therapies. J Oncol Pract. 2009; 5:18–20.
17. Emmerich J, Dumarcet N, Lorence A. France's new framework for regulating off-label drug use. N Engl J Med. 2012; 367:1279–1281.
18. Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell TJ. Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust. 2006; 185:544–548.
19. Friedman LS, Richter ED. Relationship between conflicts of interest and research results. J Gen Intern Med. 2004; 19:51–56.
20. Riaz H, Raza S, Khan MS, Riaz IB, Krasuski RA. Impact of funding source on clinical trial results including cardiovascular outcome trials. Am J Cardiol. 2015; 116:1944–1947.
21. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso-Coello P, Atkins D, Kunz R, Montori V, Jaeschke R, Rind D, Dahm P, Akl EA, Meerpohl J, Vist G, Berliner E, Norris S, Falck-Ytter Y, Schünemann HJ. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. J Clin Epidemiol. 2013; 66:151–157.
22. Park S, Lee SM. Evidence-based healthcare and the need of conditional decision. J Korean Med Assoc. 2011; 54:1319–1329.
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