What is Off-Label Medication Use
Off-label use is when a medication is used for a condition (indication) when it is not listed by regulators as a treatment for that condition.
Drug Indications
A drug (medicine) indication is when a medicine is appropriate for a particular condition. In an ideal world this will be on the basis of good quality, strong medical evidence. Unfortunately, the best-quality evidence is not always available so a judgement on the basis of experience or expert consensus may be made.
An approved indication is when a regulator officially approves the use of the medication.
Regulators realise that medicines have more than one use and they can’t keep up with all medical developments. This is why regulators do not prevent doctors from prescribing medications for unapproved indications. On the contrary, the standard treatment for many conditions involve the off-label use of medications.
How do Off Use Medicines arise?
Simply put, regulators are not able to keep up with the latest research developments in medicine.
There are literally thousands of medical research studies underway at any given moment. It would be an impossible task for regulators to keep up with every single new medical development.
How Common is Off-Label Use?
The off-label use of medications is very common. This is especially so for generic drugs. Patents for medications last for around 20 years, however, half of this time is often used up during development. Once a patent expires the medication becomes ‘generic’. Without patent protection, generic drugs can be manufactured by any company which substantially reduces their cost (and profitability).
Therefore, there is limited incentive to undertake expensive trials to provide the high-quality evidence required to obtain approval for new indications, even when these indications become more common.1Stafford RS. Regulating off-label drug use–rethinking the role of the FDA. N Engl J Med. 2008;358(14):1427-1429. doi:10.1056/NEJMp0802107
As a result, the off-label use of medications is very common. Studies have estimated that 25-31% of all medicines are prescribed off-label.2Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166(9):1021-1026. doi:10.1001/archinte.166.9.1021 Another study in 2009, found that 62% of paediatric visits involved off-label prescribing. Specialists are more likely to prescribe off-label than general practitioners.3Bazzano AT, Mangione-Smith R, Schonlau M, Suttorp MJ, Brook RH. Off-label prescribing to children in the United States outpatient setting. Acad Pediatr. 2009;9(2):81-88. doi:10.1016/j.acap.2008.11.010
Does it mean treatment is unsafe?
No.
Off-label use of medication is common and normally appropriate. There are even consensus management guidelines that include include the use of off-label medication.
Off-label use does not mean it is unsafe, untested or bad. An approved indication simply represents increased certainty that a medication is safe or effective.
Why do Drug Companies not Update their Indications?
There are usually several reasons for this. When medicines are developed, there are usually a handful of key indications that a drug researches. This indications chosen for several reasons, which includes how easy it will be to prove efficacy and the size of the population that could benefit from the medication. This means that difficult conditions or rare conditions are more likely to be neglected.
Once a medication is approved for one indication in a jurisdiction, doctors are allowed to prescribe the medication for other indications if they believe it is safe and effective.
Obtaining regulatory approval for an indication can be very expensive and time consuming. Some have estimated a standard three-phase clinical trial can cost millions of dollars.4Herper M. The Truly Staggering Cost of Inventing New Drugs. Forbes. A 2010 review calculated that it can cost USD$1.8 billion and over 10 years to develop a new medication.5Paul SM, Mytelka DS, Dunwiddie CT, et al. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat Rev Drug Discov. 2010;9(3):203-214. doi:10.1038/nrd3078
If a medication is approved overseas, why is it not approved in NZ?
There could be several reasons for this, however, it likely comes down to cost.
New Zealand is a small country and the number people that could benefit from a particular indication will be small. It still costs tens-of-thousands of dollars to have a drug indication approved by Medsafe New Zealand.
Even if there is good quality evidence about a medication and no further studies are required, the drug company may decide it costs more to get regulatory approval than likely sales from the medication in New Zealand.
Unapproved Medicines and Section 29
Due to New Zealand’s small size, there are several situations where a medication has been approved overseas and has not been approved for any indication in New Zealand. This would be an Unapproved Medicine
In New Zealand, the use of medications are governed by The Medicines Act 1981. Section 29 of the Act allows the supply of unapproved medicines to doctors (not pharmacies). The supply of unapproved medicines needs to be notified to the Director-General of Health (delegated to Medsafe) with patient details.6Medsafe New Zealand website: medsafe.govt.nz
Advertising of Off Use Medicines
In most jurisdictions (including New Zealand), advertising of the off-label use of medicines is not permitted.
For this purpose, the definition of advertising includes a clinic website. This is why some website pages may seem vague or missing information about common, but unapproved indications for medicines.
Who are the Regulators in New Zealand?
The regulator for medicines in New Zealand is Medsafe. Their full name is the New Zealand Medicines and Medical Devices Safety Authority.
The ASA (Advertising Standards Authority) plays a role in regulating the advertising of medicines and medical devices.
