On- and off-label prescribing means different things to eye care professionals in different countries. In the context of myopia management, these designations apply to medications like topical atropine, as well as medical devices such as spectacles or contact lenses. What does this mean in terms of clinical practice? Does this restrict prescribing and influence informed consent processes?
The terms 'unlicensed' and 'off-label' are sometimes interchanged, as both describe using a licensed medicinal product outside of its approved particulars.1 In myopia management, the term 'off-label' is also used for prescribing commercially manufactured and regulatory approved medical products for non-approved treatments, such as low concentrations of atropine and some contact lenses.2
On-label and off-label prescribing of medications
In terms of topical atropine, off-label prescribing applies because the medication is commonly compounded, as there are very few commercially manufactured options for the low concentrations prescribed for myopia control. Compounding medications is necessary when a commercially manufactured drug is not available which meets the unique needs of an individual patient.1 This could be changing the delivery of the medication type (eg from a tablet to a liquid) or changing its concentration - in the case of atropine, from the commercially manufactured 1% down to the low 0.01% to 0.05% concentrations typically prescribed for myopia control.
Compounding can result in safe and effective medications, and their prescribing is widespread. By virtue of being individually formulated, though, these medications are not regulatory approved and cannot be verified for their consistent stability and efficacy as for manufactured drugs.1 Compounding of atropine could influence its efficacy: read more in Compounded Atropine For Myopia Control: Safe And Effective Prescribing.
On-label and off-label prescribing of medical devices
Most eye care professionals have heard of 'FDA approval' of medications or medical devices, which applies within the USA: indicating an approval given by the US Food and Drug Administration (FDA) that a drug or device has been verified as safe and effective for particular conditions in particular patient demographics. Prescribing this same approved drug for unapproved uses - for patients who don't fit these particular conditions or demographics - is considered off-label.
Outside of the USA, CE Approval is widely recognized. A medical product which is designated a 'CE' marking has been approved by the the notified body to meet a standard of safety, efficacy and quality under specified conditions (eg. target population / indication). Some countries outside of Europe also recognize CE marking within their own regulatory processes (i.e. Australia, Singapore, Turkey, etc.)
An example of off-label prescribing of a medical device is where an orthokeratology lens, which is FDA approved or CE marked for myopia correction in adults, is prescribed for myopia control in children.3 Off-label use cannot be marketed by companies, and while not illegal for practitioners to prescribe, requires additional informed consent processes.
When it comes to myopia management, an on-label treatment has been tested and regulatory approved specifically for slowing myopia progression. Off-label treatments may very well be evidence-based, but these products have not passed the regulatory hurdle to confirm that they have met standards of safety, efficacy and quality in the target population, being children with myopia.
The International Myopia Institute Industry Guidelines and Ethical Considerations for Myopia Control Report4 states that "eye care professionals (ECPs) are encouraged to rigorously apply informed consent processes whenever prescribing or recommending off-label treatments for myopia control." Employing shared decision making and "disclosing the nature, risks, benefits, and alternatives for each myopia control treatment is vitally important."4
Is off-label prescribing safe and legal?
Off-label prescribing is not necessarily unsafe, nor is it illegal. In medicine, off-label prescribing to children is common due to a lack of pediatric-specific data regarding the dosing, efficacy and safety of medications regularly prescribed to children.5
In myopia management, off-label prescribing refers to treatment options not approved for that particular treatment by a regulatory body in a country or region. This may be relevant in your country of practice, or it may not. The International Myopia Institute Clinical Management Guidelines2 state that the "practitioner should be aware of regulatory and professional requirements regarding use of off-label treatments in their country of practice. The definition and legality of use of off-label treatment varies significantly across the world, and the practitioner should ensure [that] they understand the legislative, regulatory, and professional aspects of off-label prescribing in their country. For example, in the United States, off-label treatment is defined as “FDA-approved drugs/medical devices used for non-approved indications,” which is considered legal as long as there is sufficient evidence supporting the efficacy and safety in such application."
It is crucial to ensure that you have met any requirements for off-label treatment disclosure and informed consent in your country.
Informed consent can take written and verbal forms, and involve a variety of resources including hard copy and digital forms. It involves a patient (and/or guardian, in the case of children) with decision-making capacity, who freely authorizes a treatment plan aimed at a mutually acknowledged treatment goal. Consent is 'informed' when the eye care professional has disclosed and the patient / guardian understands the diagnosis, relevant treatment options (including no treatment) and any respective risks and benefits. This process should be thoroughly documented.6
To help you with this process, Myopia Profile has provided a free-to-download template Informed Consent Form for Myopia Management which can be edited to suit your practice requirements. Read our article Keys To Communication In Myopia Management, and you can learn a lot more about communication and informed consent in our online course Communicating the Myopia Message. In addition, industry may provide their own informed consent templates along with their products.
This educational content is brought to you thanks to unrestricted educational grant from
- Donovan G, Parkin L, Brierley-Jones L, Wilkes S. Unlicensed medicines use: a UK guideline analysis using AGREE II. Int J Pharm Pract. 2018 Dec;26(6):515-525. doi: 10.1111/ijpp.12436. Epub 2018 Jan 30. (link)
- Gifford KL, Richdale K, Kang P, Aller TA, Lam CS, Liu YM, Michaud L, Mulder J, Orr JB, Rose KA, Saunders KJ, Seidel D, Tideman JWL, Sankaridurg P. IMI - Clinical Management Guidelines Report. Invest Ophthalmol Vis Sci. 2019 Feb 28;60(3):M184-M203. (link)
- Menicon Bloom White Paper, ‘Why CE Approval Matters’, May 2019 (link)
- Jones L, Drobe B, Gonzalez-Meijome JM, Gray L, Kratzer T, Newman S, et al. IMI - Industry guidelines and ethical considerations for myopia control report. Invest Ophthalmol Vis Sci. 2019;60(3):M161-M83. (link)
- Allen HC, Garbe MC, Lees J, Aziz N, Chaaban H, Miller JL, Johnson P, DeLeon S. Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature. J Okla State Med Assoc. 2018 Oct;111(8):776-783. (link)
- Hall DE, Prochazka AV, Fink AS. Informed consent for clinical treatment. CMAJ. 2012;184(5):533-540. (link)