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Refining the system: Improving patients’ access to medicine

Published on 25/09/17 at 10:39am

The MHRA and NICE have been slowly improving the ways that the UK’s patients access medicines, but now Brexit threatens to pull the rug from under the changes. Ben Hargreaves focuses on the improvements EAMS has brought and other subtle changes that are helping patients in need.

In the UK, a smooth journey of medicine to the patient has always been of the utmost importance, but never more so than in the wake of the Brexit decision. The country could potentially face the dual difficulties of not only trying to keep costs low, but also to ensure that its patients are at the front of the queue to receive the treatments in the first place. After Brexit, the desire to bring novel medicine to the UK’s shores could wane in favour of larger population groups or through more efficient regulatory systems. For instance, Japan has a larger population than the UK but gains access to medicines later through the pharmaceutical companies’ desire to pursue access to the EU market first.

Up until recently, exactly how the UK planned to go about navigating this tricky two-step was an unknown – there were many options mooted but no firm stances had been adopted. However, Health Secretary Jeremy Hunt and Greg Clark, Business Secretary, recently broke cover in a letter to the Financial Times to reveal their desire to maintain cooperation with the EU over drug regulation. At this stage, with May’s government weakened and her own position shaky, it makes sense for the government to settle some industry nerves with news in line with industry desires, to continue business as usual in spite of Brexit.

Whether May had actually given her endorsement to the letter remains open to question, as the government had, up until that point, kept its cards notoriously close to its chest. This tactic has frustrated all industries that have been understandably keen to know how they should plan for their futures, but has been particularly harmful to those within the business of delivering medicines to patients. In one of the most heavily regulated industries, not knowing how the framework of drug approvals and access is going to work is more than a passing issue.

The letter itself read: “The UK is fully committed to continuing the close working relationship with our European partners. Our aim is to ensure that patients in the UK and across the EU continue to be able to access the best and most innovative medicines and be assured that their safety is protected through the strongest regulatory framework and sharing of data.”

Hunt and Clark’s attempt to signpost their preferred direction for negotiations was warmly welcomed by industry. For the pharma industry’s part, the ABPI’s Chief Executive, Mike Thompson, commented on the release: “This letter is a welcome recognition that the future of medicines regulation is a key priority for the Government as we negotiate a new relationship with the EU. It also signals a readiness to take a pragmatic approach to Brexit negotiations that put people’s health first. This is a great first step and we look forward to seeing more detail in the coming weeks and months.”

The key suggestions within Thompson’s response are the suggestion of drug regulation being a ‘priority’ and the need for a ‘pragmatic approach’ to be taken. The message from the industry is clear: give us a definite direction in which we are heading, and do it quickly.

There are some serious worries within the industry that drug regulation, and patient access to medicines as a result, is an afterthought in ministers’ plans for Brexit. It is widely accepted that the EMA is a leader in terms of its regulatory framework across a number of borders. Within the industry, it is understood that the UK’s position within the EMA is one that should be protected, and there is a certain shock regarding what a hard Brexit could mean for patients’ access to medicine.

One of the troubles with Brexit is its uncertainty – nobody knows how negotiations and planning will pan out. The UK’s regulatory authorities have been steadily implementing changes and improvements to ease patients’ access to medicines, many of which are only just beginning to reveal their potential. The current system that is working within the UK has been refined rather than revolutionised, as could potentially be seen post-Brexit. Though it is not a perfectly working system, there have been a number of changes that have been welcomed by the industry and patient groups.

Promoting EAMS of access

It is with the challenge that Brexit poses in mind that it seems fitting to outline the ways in which the MHRA and NICE have and continue to implement changes to speed up patients’ access to medicine. Though not all changes have been welcomed with open arms, the resilient manner with which the organisations have handled current pricing pressures could see them react just as strongly to the hurdles presented by Brexit.

The Early Access to Medicines Scheme (EAMS) was launched as a means of providing access to medicine that had not yet been approved but that could potentially provide an unmet medical need. Pharmafocus approached the MHRA to gain insight into how setting up the EAMS had gone and what it has planned for the future. A spokesperson from the MHRA explained the reasons that the EAMS was set up:

“The EAMS was launched in the UK in April 2014, following a recommendation from the Ministerial Industry Strategy Group (MISG) for an early access scheme, with additional input into the scheme’s design via a Public Consultation and an expert group on the innovation in the regulation of healthcare under the Prime Minister’s Strategy for UK Life Sciences.

“MISG concluded that whilst access to such medicines will – at least in most cases – be towards the end of the formal development stage, the scheme could still provide potentially life-saving treatments up to a year earlier than at present. Thus the aim of the scheme is to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need.”

The last drug, at present, to have made its way through the EAMS process is Santhera’s drug, Raxone. The EAMS approval means that eligible patients suffering with Duchenne muscular dystrophy (DMD) will have access to Raxone to treat their condition, with clinical studies proving that the drug has the ability to slow respiratory decline, one of the lead causes of death in DMD. To gain more information on the approval and their own experience of interaction with the MHRA, Pharmafocus spoke to Santhera’s CEO, Thomas Meier:

“The EAMS programme is meant to provide an early access prior to the regulatory approval and before pricing and reimbursement is settled in the UK. This allows Santhera to provide Raxone to patients with DMD to treat loss of respiratory function – a highly unmet medical need in DMD. Under the EAMS, Raxone will be made available to patients and need under real world conditions allowing treating physician to become familiar with the drug.”

This point is particularly interesting because there may be some that question what the positives are of entering their drugs into the scheme are; there is no financial reimbursement for the medicine provided to patients and, with the drug being taken in the real world setting, there is the possibility for unexpected adverse events to occur outside of the strict clinical trial environment. However, it does allow for both patients and, as Meier’s notes, physicians to begin use of the drug early to gain an understanding of its benefits.

Meier shared one of the observations he had made about the EAMS scheme and pointed towards a future direction the MHRA may take:

“I would like to add that as of today there were 16 drugs approved under the EAMS, three of which are currently active, the remaining 13 have expired. Currently the majority of indications for which drugs were approved under the EMAS were cancer drugs, or drugs treating infections or heart disease. Raxone is the first neuromuscular drug approved under the EAMS. We were very much encouraged by DMD patient organisations in the UK to consider application for the EAMS, and the positive opinion was very much welcome by these organizations.”

The number of drugs that has passed through the EAMS in the three years since it has been running appears to be of a relatively low number given the scheme has been running since April 2014. However, the scheme is predominantly used in areas of rare disease, where there is unmet medical need. It has also, as mentioned, been used primarily for treatments within oncology and, as is clear from Meier’s comments, it seems the MHRA are keen to broaden this to other treatment areas.

When pushed on Santhera’s experience dealing with the MHRA, Meier was very positive about the regulatory process:

“The MHRA did a full review of our dossier, which is the same as currently being reviewed by the CHMP. Following their careful assessment, the review team had a number of questions that we had to answer. Both sides had limited timelines for review and for providing the answers, but the MHRA were very cooperative in the interactions with us.  On two occasions, they asked whether we could potentially send our answers a few days ahead of the anticipated timeline because they could then bring the dossier to their next meeting, which streamlined the process. In the final stage of the procedure, we were almost in daily contact which was very helpful. I have only very positive feedback from our interactions with the MHRA.”

One of the major difficulties that the MHRA faces is to ensure that patients in need receive the medicine that can improve their condition against maintaining thorough safety reviews – a dilemma that has become increasingly important as figures such as President Trump place pressure on the FDA to speed up the process by potentially compromising safety regulations. Pharmafocus asked how the MHRA manages to maintain an objective judgement:

“There's always a balance to be struck when making decisions involving approving medicines. MHRA has a long history of experience of making benefit risk decisions, having been the leading Member State in Rapporteurships for the EMA centralised procedure for a number of years.

“The agency also benefits from external independent input from practising clinicians and other professionals through the Commission for Human Medicines and our therapeutic Expert Advisory Groups. For EAMS medicines we use all of these resources alongside a robust ‎pharmacovigilance and risk management plan strategy.”

The pricing cap question

Raxone is an example of a treatment that has benefited from EAMS scheme to provide greater access to patients but a change that was implemented at the start of the year could see approvals for rare diseases face a potential barrier. NICE announced in March that rare disease treatments must show an efficacy relative to their price tag; in particular, NICE announced on its website that: “Drugs for very rare diseases will be evaluated against a sliding scale, so that the more the medicine costs the greater the health benefit it must provide in order to be approved for routine NHS use by NICE.”

The update to its previous policy saw the maximum limit of cost for quality-adjusted life year (QALY) increase from £100,000 to £300,000. Ostensibly a positive piece of news for those bargaining to have their more expensive treatments pass through NICE’s cost-effectiveness evaluation. However, it arrives with a caveat – the total cost of all treatments cannot surpass £20 million over a three-year period.

Should a treatment hit this figure, there will be a further stage to price negotiations with NHS England. By NICE’s own estimates, this was likely to result in one in five of drugs going through further negotiations with the NHS. Essentially, the aim is that the NHS will be able to use these added discussions to barter the price of the medicine.

Obviously, the carrot is the market that the drugs gain access to, but what is the stick to compel pharmaceutical companies to the table? The answer is a potential delay of three years to market. Previously, NHS England had to ensure medicine reached the patient 90 days after NICE had approved the drug as being cost-effective. Now, it has been given the ability to potentially stall the release of a drug for three years whilst it drives a harder bargain to lower the cost of an offending medicine.

The ABPI has reacted strongly by applying for Judicial Review of the change, with Thompson releasing a statement after its actions came to light explaining the decision. He said, “These new arrangements will delay access to cost-effective medicines and deny treatments to patients suffering from rare diseases. After many months of raising concerns with NICE, NHS England and the Department of Health and offering to work constructively on alternative proposals, we have applied to formally challenge these proposals in court.”

He continued, “We believe this to be the right course of action due to the potential damage these changes will cause to NHS care and on our ability to research, develop and use new medicines here in the UK. We hope that the Government will reverse the changes and work with us to find a solution that works for everyone.”

As Thompson mentions, the area of rare disease is delicately balanced, with R&D costs being weighed against needing to charge an increased cost to make such efforts worthwhile. It means that rare disease treatments are invariably more expensive, but this might simply indicate that the population level treated is lower. In such a case, the £20 million cap across three years may be met rapidly and, as mentioned by Thompson, potentially dissuade companies from persisting in low-population treatment areas.

It has also lead to 200 rare diseases charities uniting to campaign against the changes to NICE’s method of reviewing cost-effectiveness of treatments, with a particular issue being the QALY method of adjusting benefit, a system based upon years added to a person’s life when many rare diseases are chronic rather than life-threatening conditions.

The Genetic Alliance, which headed the coalition of charities, released a statement regarding the revisions: “The restrictive proposals, alongside an already restrictive regime at NHS England for innovative rare disease treatments, will mean that more patients and families in the UK will not receive the life changing treatments that they need. Alongside proposals for potential delays to implementation of NICE guidance for treatments which fail the £20 million budget impact test, this sends a negative message regarding the UK’s attitude to innovation in healthcare.”

The key driver behind the decision to implement this £20 million review cap is funding. It is well-known that the NHS and the government are trying to cut the service’s cloth whilst not leaving patients out in the cold. Finding the solution that manages both is no easy task. One potential piece of the jigsaw, which could be both cost-effective and medically effective, is to harness the developing potential of technology.

Digital Solutions

With price at the centre of debates regarding innovation, it should come as no surprise that some of the new methods of finding value for the health service should involve technology.

New digital technologies for health are being developed at a rate commensurate with advances seen in other consumer areas, such as wearable tech. Progress has been made to such an extent that digital technologies are now being considered as valid therapeutic options in their own right that are just as effective as medicinal treatments, but far more easily available.

As a result, this method of treatment would be far more cost-effective. NICE, alongside NHS England, have begun to encourage the application of digital therapies with a goal of widespread introduction. Pharmafocus reached out to NICE for comment on how they are encouraging those that are able to develop such innovation to apply for support:

“NHS England is working with NICE to support a new digitally enabled therapy assessment programme, where up to 14 digital therapy products will be assessed for use in NHS Improving Access to Psychological Therapies (IAPT) services by 2020. This will help expand provision of psychological therapies, as well as improving access to digital services – both goals set out in the Five Year Forward View for Mental Health.

“Digitally enabled therapy is psychological therapy that is provided online or through mobile applications, with the support of a therapist. There is evidence to show that these therapies can achieve comparable outcomes to face-to-face therapy, when the same therapy content is delivered in an online format which allows much of the learning to be achieved through patient self-study, reinforced and supported by a suitably trained therapist, and also that many people prefer to access therapy in this way.”

There are inevitable questions regarding why the digital path would be taken in mental health issues, but, as mentioned by NICE, technology has become such an everyday part of people’s lives that it can be preferred. It is a forward-thinking plan that may be able to alleviate the issues faced by the UK, with PwC finding as many as one in three employees were found to suffer from mental illness in a report published in July. On top of this, levels of funding are also a cause for concern, with NHS Providers’ report claiming that 80% of mental health providers are concerned over funding levels, and 62% of those reporting that they were facing increasing demand for their services. Any additional support that can be provided patients can then only be viewed as a positive step.

NICE further explained the programme and how it will be thorough in its analysis of which technologies provide genuine medical benefits:

“The aim of this programme is to find good quality, evidence-based digital therapy packages for use in IAPT services. This will be achieved through a three-stage process:

-          Products will be selected in accordance with NICE’s selection and prioritisation criteria, following advertisement and an open application process via NICE’s portal.

-          Next, NICE will lead an objective, transparent assessment process and produce an ‘IAPT assessment briefing’ (IAB). The IAB is not NICE guidance; it is advice that will contain an objective description of each technology, an evidence summary and some comments by clinical experts. A panel of impartial experts, including experts by experience, will review the IAB.

-          Products which are deemed by the panel to meet the required levels of effectiveness, content, digital standards and resource impact will then progress to the third phase, during which they will be evaluated in practice by IAPT services for up to two years. The evaluation will consider performance and activity data as well as feedback from therapists and service users. A report on each of the products will be published following this evaluation phase.

“In terms of assessing the benefits of the technologies, there are, of course, similarities and differences when compared with how NICE assesses other medical technologies or pharmaceuticals. The critical appraisal of the published evidence of clinical benefits will be similar to other programmes in NICE: we’ll be looking at the level of evidence available for each technology; the design, quality and size of the studies; what the outcomes are, and how these would relate to the NHS care pathway. The digital technical assessment will look at the specific elements of the technologies, including data privacy, safety, usability and accessibility, and technical stability. We’ve been working with colleagues at NHS Digital to identify the best ways to assess these.”

This willingness to recognise new discoveries, though they may challenge older regulatory models, can provide real benefit to patients and to healthcare organisations, particularly in terms of increasing access to treatments, whatever their form.

MHRA has also reacted to medical innovations by setting up an office specifically designed to help and facilitate the patient access to products and devices that do not fit comfortably through its current process:   

 “Parallel to the EAMS scheme, we have also set up the MHRA Innovation Office which provides free regulatory advice and guidance to innovators developing a broad range of medicinal products and medical devices – particularly those that challenge the current regulatory framework,” the MHRA told us. “Depending on the scope and complexity of the enquiry, the advice may include input from other agencies (in the context of regenerative medicines) or may involve a face to face meeting. A broad range of researchers from academia, the NHS, SMEs and large pharmaceutical companies now make regular use of this service.”

The flexibility that both NICE and the MHRA, alongside the NHS, are displaying in such adaptations will be useful precursors to the grey territory they may enter post-Brexit. Both will know that patient expectations will still be high; cost of treatments do not enter people’s minds when those they are close to, or they themselves, are ill, and so they will have their work cut out to adapt to the changes quickly.

The MHRA provided a clue towards how they will manage patient expectation and how to provide better lines of communication:

 “The challenges involving balancing the risks and benefits are increasingly being discussed by patient groups, and involving the patient more in regulatory decision-making is a key agency objective. To this end we have started to involve patients in our reclassification of medicines, and we are looking at ways to increase patient involvement further in our work.”

The pharmaceutical industry has had undeniable shift towards involving patients more in its decisions, with patient centricity having transitioned from buzzword to an everyday part of the lexicon. This will be more important than ever as the regulatory bodies and the industry as a whole prepares to weather the storm that is hurricane Brexit. There will be teething issues that will not be exclusive to the UK, as the EMA will have to shift its headquarters without disrupting its services. Having an open and honest dialogue with patients will help to smooth the process, as well as showing the initiative to develop innovative ways to bring new therapies to patients.

Ben Hargreaves

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