I’m not a big fan of rules (as my high school record will tell you), but I am a fan of effective regulation. That same contradiction is reflected in debates around the world, prompted simultaneously by tragedy where rules seem insufficient, and frustration where common sense seems overbearing. We collectively seesaw between these views because regulation is a balance between societal safeguards and promoting individual endeavour, and judgments around this balance change over time and context.
In that spirit, the Science & Technology Committee has launched an inquiry on the EU regulation of the life sciences to consider "how EU legislation and regulation can best facilitate, and avoid impeding, collaboration and innovation in the life sciences with particular reference to the UK life sciences sector".
Regulation in medicines has been there almost since the first treatment1 but tragic events in the 20th Century, including the Thalidomide disaster, galvanised a response in the UK. The British regulatory system was reshaped and a Committee on the Safety of Drugs (CSD) was launched in 1963 together with the first voluntary adverse drug reaction reporting system (the Yellow Card Scheme) in 1964.1 Unlike other consumer goods, medicines need regulators to act in the interests of both patients and their healthcare professionals, because the evaluation of the benefits and risks requires specialised knowledge, detailed evidence and the time and resources to undertake this evaluation. Proposals to adapt these regulatory review processes are underway in Europe (including the UK), the US and elsewhere. In many cases, this is following the scientific opportunity and the evolution in regulatory science2, but not all stakeholders are assured that the robustness of regulatory review will be sustained3.
The debate revolves around the differing levels of certainty about the risks and benefits of medicines and the concerns about whether early access and adaptive pathways act to undermine regulatory evaluation. This debate contrasts with the expectations for the Access to Medical Treatments Bill, which the House of Commons has recently debated and passed last Friday. In the end, the Bill was revised to focus on the establishment of a database of "innovative medical treatments" which would allow prescribers the opportunity to review information submitted by others on treatments that have been used outside of their license, or even ahead of any potential license. Certainly, prescribers are already able to use medicines outside of their license (or ahead of any potential license), with the guidance given by the General Medical Council as well as the MHRA. The database would support that decision making in future, and we can see how more information can be useful to the prescriber in making a tough decision to treat a specific patient. What's not to like?
As with most technologies, the challenges arise not from the technology itself, but how it is used. Ultimately, the proposed database will be a collection of anecdotal data - interesting, but difficult to generalise from. In our enthusiasm for data and databases, we shouldn't forget that it is the evaluation of data - and not the data itself - that brings understanding and drives decision making. We need to anticipate how the data will be evaluated, noting again that reporting will be anecdotal, voluntary and subject to interpretation. In other words, it will be a lot more like TripAdvisor, than like the British National Formulary.
The database will provide helpful information for prescribers, as long as we all keep in mind its benefits and its risks. Some of the reporting around the debate in Parliament noted that opponents are worried by the potential to dilute safeguards, whereas supporters of the Bill "…argue it would only promote the use of drugs with good evidence behind them including in humans;…".4 Surely, that is the crux: what evidence is really presented and confirmed in the database? Would the database confer a maturity of evidence about a medicine in use that isn't warranted? Would the database encourage much broader use of a medicine in an off-label/unlicensed setting beyond the choice for a given individual where no other treatment options are available? Certainly, given the references in the Parliamentary debate and the press to NICE using the evidence from the database to evaluate cost-effectiveness, it seems likely that guidance for patients (plural) is the aim.
Which brings me to my question: are we now "over" regulation? When we decide to miss out the regulatory review step in establishing evidence about a medicine, we accept greater risks for patients and less certainty of the benefits. In specific circumstances, prescribers have to take this risk on for patients, where no other treatment options are available, but it shouldn't have to be the norm. The innovative medicines database holds great potential to help prescribers with those difficult choices, but we need to ensure that it doesn't undermine the regulatory foundation for medicines in the process. We need to be sure that the database captures both the benefits and the risks, with safety information shared quickly with the manufacturers and regulators to avoid avoidable risks to patients. Both confirming and disconfirming evidence in use will need to be captured and curated, and that will need engagement from prescribers, patients and indeed all stakeholders to agree guidelines on the scope and operating principles. Maybe we should ask TripAdvisor how they did it?
1 Rägo, L. & Santoso, B. in Drug Benefits and Risks: International Textbook of Clinical Pharmacology (eds C.J. van Boxtel, B Santoso, & I. R. Edwards) Ch. 6, (IOS Press and Uppsala Monitoring Centre, 2008).
2 Eichler, H. G. et al. From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients. Clin Pharmacol Ther 97, 234-246, doi:10.1002/cpt.59 (2015).
3 Hamel, M. B., Darrow, J. J., Avorn, J. & Kesselheim, A. S. New FDA breakthrough-drug category—implications for patients. New England Journal of Medicine 370, 1252-1258 (2014).
4 Boseley, S. in The Guardian (Guardian News and Media limited, London, 2016).