Early Access – an expanding menu of options

Getting a product to patients is not always easy but with new options for companies to consider in the UK and Europe, access may be earlier.

The importance of being early

For patients, the importance of getting timely access cannot be overstated. For some, there is only a small window of opportunity where a drug can have an impact (and give precious months of life), and even for those with long term chronic conditions, getting treatment early can help avoid or slow down disease progression. And for companies too; after spending what can be millions on research and development (R&D) and relying on revenue (in part) to fund more R&D in the future, access means a welcome revenue stream. There are a host of reasons why access might not be as timely as patients or companies want; the time to conduct research and the need to adapt the research plan, assessment of safety, efficacy, quality and overall risk/benefit by the regulator, assessment of cost effectiveness by a Health Technology Assessment (HTA) Agency, and sometimes further assessment by local agencies within the health care system. All of those are 'system' issues, before prescribers are convinced of the merits of prescribing for a given patient in a specific circumstance.

"The mantra of 'low and slow' uptake in the UK seems to have been heard"

In the UK, the mantra of 'low and slow' uptake seems to have been heard (if not loud and clear, then at least above a whisper) and companies now have a new option of the Early Access to Medicines Scheme (EAMS). And in Europe, companies can take part in the new European Medicines Agency (EMA) Adaptive Licensing (AL) pilot.

MHRA's New Early Access to Medicines Scheme in the UK

Launched only in April of 2014, this is a brand new option for companies. It's a three-stage process:

 • Stage 1: Promising Innovative Medicine (PIM) designation

Companies can apply for the PIM using early trial data. The result of a PIM designation application won't be published – whether positive or negative. But a positive PIM designation is needed to progress to an application for an EAMS scientific opinion.

• Stage 2: The Early Access to Medicines (EAMS) Scientific Opinion

MHRA review available trial data and decide whether to provide a positive EAMS scientific opinion. If it's positive, then the MHRA publishes a Public Assessment Report (PAR) and the EAMS treatment protocol. If the opinion is negative, that's not published.

• Stage 3: Commissioning in the NHS in England and the links to National Institute for Health and Care Excellence (NICE) assessment.

This stage seems particularly unclear according to the UK BioIndustry Association (BIA) and it's silent on what happens outside of the NHS in England. Mostly it seems that NHS England, as the specialist commissioner in England, will consider how to roll out use and what evidence they will want to gather.

The underlying drive is to offer earlier access – especially where a product is particularly promising – even if the clinical benefit remains uncertain, but crucially where it is seen as offering an acceptable level of safety, outside of trials. Jeremy Hunt, Secretary of State for Health in the UK, talks of "bringing hope to patients".

Estimates vary, but perhaps two, or even as many as 12 products a year, could go through EAMS. That depends on companies since it is a voluntary scheme. It depends on whether companies will want to give their product away free to the NHS, which must be a bitter pill to swallow for companies, especially after the industry just committed to paying back to the National Health Service (NHS) if the NHS branded medicines bill goes over a pre-agreed target growth rate in the 2014 Pharmaceutical Price Regulation Scheme (PPRS). And it depends if they will want to pay the fees (although they are low – consideration of PIM status is just £4,027 and the later EAMS fee is £29,000 – but still that may be tougher on smaller companies). There may also be costs of complying with EAMS requirements, since companies will need to have a risk management plan in place and may need a registry, although they would need much of that in any case. Estimates of the costs of compliance with EAMS vary enormously; from £13,000 to a whopping £3million over the lifecycle of a drug. What companies will get, is a signal that may be useful in other countries – a dossier with a positive EAMS scientific opinion could be persuasive – as well as evidence on real world use. And of course patients could benefit, if the promised clinical benefits materialise – and perhaps a year earlier than would have been the case.

But it's somewhat sad that the EAMS scheme has taken an astonishing eight years from concept to delivery. The germ of the idea for the scheme was in Sir David Cooksey's 2006 Review of UK health research funding. Not so, well, timely itself then.

New Adaptive Licensing Pilot from the EMA

Launched just before the EAMS in March 2014, the AL pilot is offering companies the chance to explore a new approach to licensing. The idea is to start with a small patient group and expand the patient group over time, by gathering evidence and adapting the licence. EMA say they want companies to come forward to test AL out, and not only companies, but all with an interest in patient access such as HTA agencies, patient organisations and those groups producing clinical guidelines.

Just as for EAMS, the focus is on timely access. Which for many, equates to earlier.

"Estimates vary, but as many as 12 products a year could go through the Early Access to Medicines Scheme"

A focus on unmet need and 'serious' conditions

Both EAMS and the AL pilot focus on those products that address an unmet need and where the condition is serious. MHRA use the terms "life threatening or seriously debilitating". EMA say that AL is for "treatments that promise to address serious conditions where there is an unmet clinical need, especially when there are no satisfactory alternative therapies".

These new options are therefore likely to be of interest to those researching orphan medicines, which are often for just such conditions. That responds to pressure by groups like Joining Jack, run by parents who have children with the rare and currently incurable disease, Duchene muscular dystrophy (DMD). They've urged government in the UK to make changes and speed up access. And one of the first products to go through EAMS could be one that looks promising for Duchene's. Joining Jack are not alone in focusing efforts, other groups like Empower Access to Medicines, have been playing a role too.

...but questions about what happens next

Both the EAMS and AL approach may facilitate earlier access but are focused on the regulatory side. What remains to be seen is how products that have been through EAMS or AL, or possibly both, will fare once they go through a cost effectiveness assessment. In England, part of the difficulty is knowing whether they will go through NICE or not, and if so will it be through the new Value Based Assessment (VBA) under construction now and to be implemented later in 2014, or if it will be through the Highly Specialised Technologies (HST) assessment. In either case, it's difficult to predict what NICE might say as VBA isn't yet rolled out and HST has only one example – Soliris (ecluzimab). In the case of Soliris, the jury is still out as NICE wants to know more about how the price has come about – and how it fits into NHS England's specialised commissioning budget. Which runs the risk of earlier access for patients as products go through licensing, but later, limited access for new patients if a cost effectiveness assessment doesn't recommend use. Does this run the risk of raising hopes, only to dash them later?

About the author:

Leela Barham is an independent health economist and policy expert who has worked with all stakeholders across the health care system both in the UK and internationally. Leela works on a variety of issues: from the health and wellbeing of NHS staff to pricing and reimbursement of medicines and policies such as the Cancer Drugs Fund and Patient Access Schemes. Find out more here and you can contact Leela on leels@btinternet.com

Have your say: Will the European and UK schemes really promote faster uptake?