20 Nov 2018
Last week we published our latest bioethics briefing note on medical treatments which are considered to be experimental (or unproven, or innovative, or novel, or unauthorised, or unvalidated). As you can see, one challenging question has been what exactly to call them.
Unproven covers the sense that there is less evidence to back their use than we would normally expect from medical treatments, but glosses over questions around what counts as ‘proven’ and whether all conventional medicine really is evidence-based. Take the investigation on medical devices in the news today, which found that some implanted devices which had marketing approval, such as spinal rods and vaginal mesh implants, have been used in patients with very little evidence to show they are safe and effective.
Innovative is often taken simply to mean ‘new’ or ‘exciting’ – as is novel – which might ring true in some of these cases but not in others. Unvalidated? Well maybe, but is that a word? Unauthorised? Some treatments offered to patients are not subject to licensing or authorisation. Surgical procedures, for example, can be introduced on the basis of little or no previous evidence or experience with much less systematic oversight than you might expect. And expensive fertility treatment ‘add-ons’ are offered by private clinics to women and couples trying to conceive despite the fact that the fertility regulator recognises that many of them are not proven to work. Non-standard, a final contender, captures the exceptional circumstances in which these treatments might be offered, but not necessarily the lack of evidence.
Language matters - this was emphasised to us at a roundtable meeting we held to explore these issues earlier this year. Whether a treatment is marketed as ‘innovative’ or ‘unproven’ might have an impact on how it is perceived, for example when questions of access comes to public attention and interest. Whether something is framed as an entirely new intervention or ‘just’ a modification of a routine treatment might tip the balance towards more or less regulation and oversight. How a doctor discusses a possible treatment option with their patient clearly matters – though we were also reminded that there are situations where patients might feel it does not matter whether a treatment is ‘unproven’ or ‘experimental’ if it represents a possibility, even if very small, of improvement or survival. Patients who have limited options might wish to access experimental treatments despite uncertainties about safety and efficacy and the often substantial financial costs involved.
Whatever you call this group of treatments, uncertainty is a key theme. Across the range of treatments we considered, uncertainty about benefits and risks leads to practical challenges, for patients deciding whether or not to seek or accept a treatment; for doctors seeking the best option for their patient; for regulators deciding whether to approve a drug or device for use; and for commissioners deciding whether to fund a treatment in the NHS. In the end we arrived at the title experimental treatments, with an emphasis on treatment – which is to say ‘not in a research trial’ where uncertainty is a defining feature and informs specific ethical and regulatory frameworks.
Though General Medical Council guidance is explicit that patients should be told when a proposed treatment differs from standard methods, there is usually no ethics committee review to decide whether or not an experimental treatment can be offered in the first place; nor necessarily any consent forms to record that the possible risks and benefits have been understood. This places particular responsibilities on healthcare professionals and others involved in offering or promoting treatments. These include avoiding hype and false promise, exercising humility in acknowledging the limits of current knowledge, and being trustworthy, for example by being aware of possible conflicts of interests that might affect the decision to offer an experimental drug or device. My colleague Katharine Wright discusses this in a previous blog post in relating to those having to make unbearable decisions about the care and treatment of a seriously ill child, something we are exploring in more depth in a parallel project at the moment.
Another important difference from research is that, with the use of experimental treatments, there is usually no requirement that the outcomes of the treatment are recorded for others to examine or learn from. In previous work we have highlighted the importance of capturing information about experimental interventions in the brain and treatments offered to children, for example through a registry or publication. A database of unlicensed and off-label prescriptions is proposed in the recently passed Access to Medical Treatments (Innovation) Act, but it is not currently clear whether such a database will be set up and if so how it would operate.
Looming just off the pages of this briefing note are wider, related issues. For example, licensing and access to treatments is not, as one might assume, the automatic outcome of the research and development process. Marketing authorisation is sought by manufacturers at the point then they are ready, willing and able to put a drug or a device on the market. This decision will be influenced by a range of factors and there is no guarantee that, just because a drug is proven to work for a particular condition or patient group, it will necessarily be licensed for that purpose. This has become clear in the recent court case about Avastin, a cancer drug widely prescribed off-label for a common eye condition. In addition, the high cost of some experimental treatments raises issues both about how pricing is determined and about the fair use of healthcare resources and funding constraints, an issue explored in another of our background papers.
Our briefing note concludes with a challenge: how can we balance the interests of patients in accessing experimental treatments and the need to support innovation, with ensuring there are sufficient safeguards to protect patients from potential harm? This challenge is particularly acute when treatments are accessed outside the UK regulatory framework, and when children are involved. With the huge political changes looming ahead for the UK in the coming years, policy makers must ensure these issues are part of the conversation.