Pragmatic Trials: RWE’s Hidden Gem
Pragmatic trials continue to be overlooked in the RWE space – particularly in the US. Can we expect to see wider stateside adoption?
According to the US National Institutes of Health’s clinicaltrials.gov database, around half of the world’s 1,800 clinical studies that have incorporated real-world data since 2006 have been set up in the last three years alone.
A record 300 real-world evidence (RWE) studies were coordinated in 2007, indicative of a growing interest in the collection of patient data beyond the traditional realm of randomised clinical trials.
The reasons for this are reasonably axiomatic. The costs around conducting randomised clinical trials (RCTs) have steadily ballooned in recent years, prompting pharma to turn to routinely-collected data as a means of creating more efficiency in their research.
But while pharma companies continue to pump vast resources in the direction of RWE implementation, the field of pragmatic trials remains comparatively disregarded. Given that such trials are faster, simpler in design and employ data that already exists in real-world practice, are players missing a trick?
Pragmatic clinical trials (PCTs) represent an attractive alternative to RCTs. Built upon reams of electronic data – such as electronic medical and health records – PCTs are essentially rooted in “healthcare settings”, as Mats Sundgren, principal scientist and health informatics director within global medicines development at AstraZeneca R&D, explains.
“PCTs are research investigations embedded in healthcare settings designed to increase the efficiency of research and its relevance to clinical practice,” he says. “It’s an approach that is increasingly supported by health authorities, as costs can be reduced by building RCTs upon existing registries and other types of electronic data.”
Yet, while PCTs can create the strong alignment of protocol with medical practice – boosting trial recruitment and participation – they are not necessarily a replacement for RCTs, argues Sundgren; rather, a modern counterweight to traditional studies.
“They don’t take away from basic science or diminish the importance of traditional RCTs – we just need a balance,” he says. “For example, in all PCT, randomised patient/treatment groups are a pre-requisite. No clinical trial is completely explanatory or pragmatic. RCTs and PCTs exist on a continuum.”
The general consensus is that Europe, home to a uniform patient database, better lends itself to the wider implementation of pragmatic trials than the US, where holistic data-gathering is perceived to be much more difficult due to its fragmented healthcare system.
But, as a nation with some of the most diverse treatment practices on earth – not to mention its vast, heterogenous population – pragmatic trials might soon take off in the US.
“The US has a number large hospital networks,” says Sundgren. “Take the likes of the Cleveland Clinic, Mayo, Veterans Association/MAVERIC – they are all connected to the same EHR systems and sharing coordinated research bases for internal claims data. These networks can serve as good platforms for conducting PCTs.
“The FDA has been very supportive in promoting PCTs; so have a number of EHR networks actors and academic research organisations. Taken together, these aspects provide opportunities for US actors to conduct PCTs.”
If PCTs are to get off the ground in the US, Sundgren believes they will need to demonstrate that they can be used for new labels and indications. “This will drive the pace forward significantly”.
But with scant evidence of such trials currently taking place, one can still only speculate over which stateside pharma companies will take the next step. What other hurdles might hinder the wider adoption of PCTs?
“Registries, EMRs and EHRs are primarily designed to support clinical care and reimbursement, and are not necessarily perfectly suited to research,” says Sundgren. “Although electronic databases are becoming ubiquitous in many developed countries, such as the US, they may not be available in all settings.”
“Furthermore, several databases may be needed to collect the data required for an individual patient. This requires central adjudication. Data must be able to support regulatory decision-making, while providing adequate information and evidence for basic decision-making. A database must provide patient protection.”
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