Mainstream medicine has long advocated for the need to move away from a patriarchal approach to care, which is top-down and prescriptive, and towards a personalised patient-centred approach that is collaborative. This is because there is no ‘one size fits all’ solution to health, or life.
What Is Off-Label and Unlicensed Use?
Unapproved-use of an approved drug is often called ‘off-label’ use – it means taking it in a way other than the instructions advise on the packet. While all legal grey areas are inherently fraught with greater complexity, supervised off-label use aims to give people more autonomy around what works for them as individuals.
One example would be when chemotherapy is used to treat one type of cancer, but healthcare providers use it to treat another type of cancer. This may be because there is some anecdotal benefit, but a lag or a lack of data from trials. However it may also be unconventional or under-practiced due to fears around litigation. This is the case for many emerging industries such as that of clinical cannabis use – which in itself advocates for greater variability in dosing guidelines.
Off-label use is legal, and more common amongst independent prescribers. However ‘off-label’ use is different from ‘unlicensed’ use. Unlicensed means that the medicine has a license in other countries, but is not yet licensed in the prescribing country (e.g. the UK). It can also mean that the medicine does have a license in the UK, but needs to be made into a different / unlicensed format – for example a licensed pill that needs to be made into an unlicensed oil for a patient with difficulty swallowing.
Some pills with no license at all can be created for rare diseases – which are often not economically viable when it comes to running the large scale clinical trials. By taking the unlicensed medicines, the patients are themselves part of a live trial investigating on-going outcomes. One of the main aims of the off-label approach is to magnify the benefits of a medicine, while minimising the side-effects of both the medicine and the underlying condition.
However, aside from the difficulties of data handling that a more diverse lens with wider variables proposes – care providers face greater legal uncertainties, and patients do not have access to some of the information required for truly informed decisions. For example, individual outcomes are highly dependent on genetic makeup – meaningful insights into which, are still lacking and not widely accessible.
The ethical justification for off-label prescribing is that it can provide the best available therapy for a particular person. Concurrently, the ethical justification for conducting clinical trials, is to develop new therapies and to clarify the best use of existing treatments for future patients.
Off-Label Isotretinoin (Roaccutane)
As an example, the gold-standard solution for treatment resistant acne is oral isotretinoin (13-cis retinoic acid, or brand name Roaccutane). Acne Vulgaris is a chronic inflammatory skin condition affecting the face, back and chest. It is characterised by blockage and inflammation of the pilosebaceous unit (the hair follicle, hair shaft and sebaceous gland).
While this is considered an aesthetic problem – it can permanently scar the skin and have a detrimental impact on social wellbeing, confidence and mental health. The root causes of the condition are not well understood, and there are many stubborn myths about links to lifestyle factors such as poor hygiene or dietary modifications. Such myths place an unjustified amount of pressure on the individual to adopt restrictive practices, with limited results. On top of this, they are frequently leveraged to market ineffective cosmetic treatments to the desperate.
Over the counter solutions are futile in the face of clinical acne because they have no effect on the root causes, but obtaining prescription treatment is a lengthy, multi-stage process. The first line of care is usually topical solutions such as prescription benzyl peroxide, before moving onto oral antibiotics and finally reaching a specialist dermatologist appointment for Roaccutane or similar medication.
Roaccutane is such a closely guarded secret due to its notorious side effects – including photosensitivity, suicidal ideation, sore, dry and bleeding mucosal surfaces, and teratogenicity (foetal deformities if taken when pregnant). However, under the standard dosing guidelines, the medication is taken at moderate doses, every single day, and over a relatively short timeline (for around 16-24 weeks).
In some individuals, the symptoms of acne are not found to return after such a nuclear approach, as the sebaceous gland activity is permanently damaged – or fixed, given that it was initially overactive… However many people have been finding greater benefits, and a more tolerable process, with a slower and steadier, off-label approach.
No biochemical links to the side effects of suicidal ideation have been found – it is speculated that there might be some link to changes in metabolism in the frontal lobe of the brain. However the extremely painful, bleeding skin and dry mucosal surfaces (eyes and mouth), caused by taking such a medication so intensively in and of itself, would also be enough to propagate such feelings. Because these effects are a subjective, intangible and qualitative element of treatment (not biochemical), the link is not formally established in trials.
It is therefore unsurprising that the popularity of off-label use is rising and demonstrating long-term benefits. Aside from acne, some of the other most promising off-label indications include seborrhea, seborrheic dermatitis, severe rosacea, non-melanoma skin cancer chemoprevention for at-risk patients, and advanced photoaging with multiple actinic keratoses.
Roaccutane possesses many properties and may influence skin cellular processes by modifying gene expression (it gets to the root cause by working on an epigenetic level). The exact mechanism of action is unknown, but several studies have also shown that it induces apoptosis (programmatic cell death). It should still be taken under the guidance of a professional because it should not be taken if there are contraindications (liver disease, pregnancy etc) and requires blood monitoring.
Getting access to off-label use of a medication ultimately rests in the hands of the prescriber. However if patients cannot get hold of a medicine in their prescribing country, they will often turn to an unregulated black market in which scams and counterfeits are rife, or exploit variations in international guidelines. Although Roaccutane is a derivative of vitamin A, it is ineffective to substitute with vitamin A supplements because they are not processed, studied or regulated well enough for such conditions.
Many journals acknowledge that the use of Roaccutane in dermatological conditions other than acne has continued to increase. Its successful implementation in these conditions suggests that it has a broader spectrum of uses than initially considered, and they maintain that randomised clinical trials would help clarify when and how systemic Roaccutane should be employed, in order to judiciously maximise the capacity of such treatment.
Alternative healthcare treatments such as herbal remedies suffer from the opposite problem – they are criticised for a lack of scientific rigour and standardisation, but the aspect of personalisation is baked into their founding philosophy. The clinical trial format is also mostly designed for isolated extracts, whereas many traditional approaches rely on a preparation that is inherently holistic. Most of these compounds are required to work in synergy (for example cannabis and its ‘entourage effect’).
A happy medium needs to be sought that brings greater clarity to the chaos of the grey area – where context is king and nuance is no longer negative. This starts with asking better questions over seeking absolute answers, and accepting that a non-binary existence is not reduced to either/or format, but finds greater stability in the ever shapeshifting variabilities of the scope, scale and focus in question.