One of the earliest and most pronounced impacts of the UK’s vote to leave the European Union was the loss of the European Medicines Agency (EMA). Long headquartered in London, the EU drug regulator is now severed from the country both physically and systematically, with its base now in Amsterdam and the UK now assessing drugs through its own regulatory agency, MHRA.
This leaves the UK’s drug pricing watchdog, the National Institute for Health and Care Excellence (NICE), in an uncertain position. Once a leading voice in health technology assessment (HTA) in both Europe and the wider world, the body now finds itself unable to work as closely with the EMA – and by extension countries in the EU – as it did in the past.
Emmanuel Lacharme, previously a technical analyst at NICE and now senior consultant, global health economics and outcomes research at ICON, is confident that NICE’s existing reputation will help it maintain its global standing in the immediate future – but notes that there is still a risk the body will become “isolated” as a result of Brexit, particularly as companies are no longer able to rely on the EU’s centralised approval system for the UK.
“There will be uncertain times, but also new opportunities,” he says.
“I believe that NICE will try to do as much as possible to support our industry, by offering early engagements and a streamlined MHRA and NICE parallel approval process. Practically though, there are risks of additional processes and requirements (and expense) for pharmaceutical companies. This additional effort could lead to poorer patient access.
Caroline Delaitre-Bonnin, senior principal, global health economics and outcomes research at ICON, notes that this could lead to companies no longer seeing the UK as an early launch market.
“The UK has traditionally been an early launch market for pharmaceuticals partly because UK prices are often used as a reference price for other countries, and also because NICE assessments are held in high esteem. Brexit could change this.
“It’s difficult to say whether NICE will maintain the same leadership position in Europe that it has in past years.”
Lacharme points out that NICE does, at the very least, have a very strong foundation to build upon.
“NICE has always been a great reference in HTA for cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) of new medicines,” he says. “For example, its 2013 guide to the methods of technology appraisal is still a valid reference to understand the key principles of cost effectiveness within an HTA context, and NICE decision support unit documents are a useful resource for any health economist needing technical or educational support.
He adds that NICE’s strong reputation is also due to its openness to industry involvement and collaboration.
“The current public consultation period for the NICE methods review is one example of this.”
With NICE having had a significant influence on the development of other HTA authorities’ methodologies over the last 20 years, Manpreet Sidhu – ICON’s executive principal, global health economics and outcomes research – says the agency’s influence has a good chance of remaining robust over the coming years.
“NICE is still considered to offer a transparent and clear methodological framework for regulators and companies, and so whilst the intricacies of working in a post-Brexit world are ironed out it would seem unlikely that pharma companies/regulators would move away from continuing to engage with NICE.”
And while the largest impact is likely to be companies launching in the UK no longer being able to use centralised EMA submissions process, Sidhu notes that the evidence requirements of NICE and EU countries have not changed.
“There is some work to do with respect to aligning methodologies and streamlining these requirements across all of the EU to facilitate the process of evidence generation for pharma companies, but that need exists without Brexit.”
Because of this, Sidhu says it will be important for NICE to continue to lead discussions on methodological perspectives within HTA bodies if it wants to maintain its reputation.
“Being a flagship HTA, where other HTA bodies look to NICE methodologies as a signpost, has been great for the agency,” she says.
“To continue on that trajectory NICE needs to continue engaging with other HTA bodies on joint commissioning of advice and guidance, and utilising cohesive methodologies.”
In fact, NICE has not stopped working with global agencies on collaborative methodologies – one example being the Orbis Project, a joint programme involving the US, Canada, Switzerland, Singapore and Brazil that aims to review and approve promising cancer treatments months ahead of the EU.
“NICE is conscious of its key role in HTA,” says Lacharme, “and it wants to be sure that the UK remains a destination of choice for the life sciences sector. It is still working collaboratively with global health system partners, and more particularly with the MHRA, to design a streamlined process for licensing and evaluating new medicines.”
NICE has long had significant clout in these early dialogues. The agency was one of the first HTA bodies to offer regular activity on early scientific advice, which strengthened its influence across Europe.
When the European Network for Health Technology Assessment (EUnetHTA) was founded in 2006 to help provide parallel early dialogues from multiple HTAs across the region, NICE was one of the most frequently selected bodies for companies to consult with, further strengthening this influence. In fact, getting advice from NICE as part of a parallel dialogue was more popular than talking to the agency alone.
Currently there are two main options for parallel early dialogues via EUnetHTA – EMA-EUnetHTA consultations, where companies consult with both HTA bodies and the EMA itself, and EUnetHTA multi-HTA dialogues, which take into account the opinions of HTA bodies only.
Pre-Brexit, NICE was particularly invested in early dialogues involving the EMA, but now, although it remains a part of Europe’s Early Dialogues Working Party (EDWP), it can only take part in parallel dialogues that don’t involve the regulator.
Delaitre-Bonnin says that NICE’s continued relationship with the EDWP will be key to mitigating the potential negative impacts of its isolation from the centralised EMA system.
She notes that the agency has already announced new approaches aiming to deliver scientific advice in similar timelines to the EMA process to help with this.
“This new way replaces the parallel advice service that NICE delivered with the EMA and is performed via the EUnetHTA.
Over the last five years the European Commission has repeatedly proposed to strengthen cooperation across HTAs in the EU, suggesting new regulations for common European HTA methods, sharing data and expertise, and common procedures across the EU.
“As the UK will not be an EU Member State, NICE and the other HTA agencies in the UK – the Scottish Medicines Consortium (SMC) and the All Wales Medicines Strategy Group (AWMSG) – will have a limited role to play in this new strategy,” Delaitre-Bonnin says.
“That is why NICE needs to organise its services in closer collaboration with EUnetHTA for multi-HTA early dialogues and introduce concurrent advice in similar timelines to the EMA.”
NICE is also looking to apply similar parallel-advice principles to other global regulators – one example being through its relationship with the Canadian Agency for Drugs and Technology in Health (CADTH).
“Moreover, NICE continues to offer advice in collaboration with the MHRA,” says Delaitre-Bonnin.
Delaitre-Bonnin believes that NICE’s continued expertise in areas such as providing detailed feedback on companies’ evidence generation plans, helping companies understand the perspective of decision makers, and providing access to patient, NHS and academic experts, means that early dialogues delivered by the agency will still be both “relevant and expected” by pharmaceutical companies.
But she adds that it’s important to keep in mind that some other HTA bodies like Zorginstituut Nederland (ZiN) in the Netherlands, which is also a member of the EDWP, have been more innovative in reviewing and changing their guidelines, and could soon emerge as strong competitors in this space.
“Meanwhile, we need to remember that multi-criteria decision analysis and value frameworks highlight that there is more to HTA than an ICER.”
She says that now the country’s market is separated from the rest of the EU, the UK could be further highlighted to the industry by strengthening early engagement and offering a fast-track MHRA/NICE parallel approval process.
“We could also imagine that this early approval in the UK might lead to opportunities to generate early-stage real world evidence that could be supportive for any other HTA submissions and pricing negotiations in Europe.”
“They are preparing for NICE and EU HTA submissions as they have done previously, knowing that things may change but also that this change is likely to be incremental.”
Nevertheless, Sidhu says it’s important that companies read up on insights from people knowledgeable about working with NICE, like those on ICON’s blog, to “future proof” development plans for assets.
Meanwhile, Delaitre-Bonnin says that ICON is advising clients in the current climate to seek parallel engagement with NICE and other regulators and HTA agencies on early scientific advice.
“The quality and the relevance of early dialogues with NICE have already been recognised,” she says, “and their value for some other European countries is likely to remain for several years to come.”
Caroline Delaitre-Bonnin – senior principal, global health economics and outcomes research, ICON
Caroline has over 15 years of healthcare experience spanning industry and consulting. Her primary focus is on HTA and value communications projects with extensive experience in oncology, haematology, gastroenterology and orphan drugs. She worked on projects in HTA submissions, developing HTA evidence development strategies to support launch products, strategic integrated scientific advice, strategic advice and developing value communication tools.
Emmanuel Lacharme – senior consultant, global health economics and outcomes research, ICON
Prior to joining ICON in 2020, Emmanuel’s experience included positions in various Paris Public hospitals (AP-HP) in clinical trials, early access (ATU), quality insurance, medical device, purchase, and clinical pharmacy (psychiatry, neurology) departments. At Novartis he worked as a project manager on market access, pricing and reimbursement in the oncology department. At the French National Authority for Health (HAS) he was a HTA analyst in economic and clinical drug assessment. At NICE he was a technical analyst in the scientific advice department.
Manpreet Sidhu – executive principal, global health economics and outcomes research, ICON
Manpreet has over 20 years of experience in health economics, including strategic evidence generation planning, project management, systematic reviews, economic modelling, strategic market access, and dossier development. At ICON, Manpreet is business lead for global health economics and outcomes research, incorporating patient centred outcomes, health economics and HTA, and value communications, and is responsible for overall project delivery and strategic direction of the practice.
ICON is a global provider of consulting, and outsourced development and commercialisation services to pharmaceutical, biotechnology, medical device and government and public health organisations. ICON focuses on the factors that are critical to clients – reducing time to market, reducing cost and increasing quality – and its global team of experts has extensive experience in a broad range of therapeutic areas. ICON has been recognised as one of the world’s leading contract research organisations through a number of high-profile industry awards. With headquarters in Dublin, Ireland, ICON employs approximately 16,000 employees in 93 locations in 41 countries. Further information is available at www.iconplc.com.
George Underwood is the editor for pharmaphorum’s Deep Dive digital magazine. He has been reporting on the pharma industry since 2014 and has worked at a number of leading publications in the UK.