A new EU project called GETREAL is investigating ways to integrate data from real-life settings into the drug development and approval process. But how can real-world data be tapped before a drug is launched? Project co-ordinator Chris Chinn explains what GETREAL is hoping to achieve.
Drug developers have long been faced with a kind of catch 22. In order to get a true sense of how a drug works – the benefits, and the most appropriate patient group – it is necessary to examine its efficacy in a ‘real life’ hospital setting. Ideally speaking, a drug would already have been trialled in this way at the time of launch.
However, for patients to access the drug in the first place, it already needs to be on the market. Clearly there is no way of obtaining this kind of data in advance.
“Typically, real world evidence can only be generated on new medicine after it’s made available in healthcare systems, and people can observe how well it performs under natural conditions,” says Chris Chinn, vice president and head of Health Investment Evidence, European Access to Medicines, at GlaxoSmithKline.
“At the time of market authorisation, HTA bodies have to predict how well the new medicine is going to deliver benefit and value once it’s in clinical practice. But there’s a lot of uncertainty at that decision point, before you’ve built up a picture of what the drug can really do.”
Clearing a route
Prediction, of course, is far from an exact science. In the absence of data from natural settings, health technology assessment (HTA) bodies are forced to rely upon data from clinical trials. This may lead to a significant degree of uncertainty, which in turn can cause delays in reimbursement and restrictions on the patient group that is allowed to access the drug.
Sometimes there is an extra obstacle to surmount. Particularly in countries like France, Sweden and Italy, development teams may be required to conduct follow-up studies after launch. Because these demands are not always co-ordinated between markets, they may be faced with a barrage of duplicated or even contradictory requests. This can introduce a further delay into the proceedings, not to mention an additional expense.
As Chinn explains: “People have been managing the best they can, but both HTA and industry recognise we’ve reached a crisis. The sustainability of the R&D business model is threatened if you don’t have a clear and predictable route to having drugs on the market reaching the patients that need them most.”
It is for this reason that the EU’s Innovative Medicines Initiative (IMI) launched its latest project, GETREAL, which will investigate new ways of integrating real-world data into the earlier stages of the drug development process. If achieved, this will strengthen the evidence base and ensure that trials are better targeted.
As the project co-ordinator, Chinn will be looking into two key questions. Firstly, how can development teams generate evidence from real-life clinical settings before the drug has hit the market? Secondly, when presenting to the regulator, how can they ensure these new and creative approaches receive the green light?
GETREAL will be a collaborative endeavour. The €16.3m project has been designed to bring all interested parties together – industry bodies, academics, regulatory and reimbursement agencies, budget holders and patient groups – with a view to accomplishing more than industry could achieve by itself.
“R&D companies have to make decisions years in advance about which research we’re going to fund, and HTA bodies are trying to make decisions with the best information possible, so it’s really important to have HTA bodies and research talking together,” says Chinn. “We need to have the regulatory partners join us was because we’re looking at development programmes prior to market authorisation. And we’re tapping into the brain power of academics as well as having key stakeholders work together in a single partnership.”
While industry bodies may themselves have competing interests, the IMI provides a safe space to pool ideas.
“Obviously at the time you launch a drug, you’re making the case that your medicine is better than the standard of care for certain patients, so it’s a competitive situation,” Chinn continues. “But the IMI was set up as precompetitive. We’re working very hard with our work packages to make sure we’re focusing on methodology, guidance and standards, rather than individual drugs”
The IMI aims to help R&D understand where they can bring certain real-world evidence techniques earlier into development, while addressing any practical or ethical issues that may arise. It seeks inform a fast-evolving area of policy, as well as forming strong links with other EU initiatives and wading into several key debates.
For instance, while we have recently seen a surge of interest in adaptive pathways for clinical trials, there is no real consensus about how you can amass the requisite evidence without taking unnecessary risks. The IMI hopes to show how some available methodologies might fit into an adaptive process, so long as the regulators and HTA bodies are on board.
It will also look into rapid relative effectiveness assessments, currently in contention as various EUnetHTA initiatives get underway. Finally, it will aim to clarify the debate about what evidence is required and when. This should allow industry to anticipate what kind of follow-up research it will need to do post-launch.
Creating a toolkit
While GETREAL launched just before Christmas, the project is still in its early stages. Up till now, it has largely been a question of getting things up and running – starting the desk work, holding preliminary workshops and compiling literature reviews.
The ultimate goal, however, is to create a toolkit: a set of practical steps that will help R&D execute inventive research in a pre-launch environment. This will come in tandem with a strong training and education programme, allowing all parties to understand the role of real-world evidence at an early stage.
“We want to determine what we can be creative about, what studies can be done while a drug is still in development, and how that will go down with the regulatory decision makers?” explains Chinn. “So what can be done, and how can it be done, and how will it be received?”
This article appears in the August 2014 edition of Pharma Technology Focus