Knowledge is power. It’s an axiom that defines all research but it is now freighted with extra meaning as industry looks to reshape the future. With waves of uncertainty from shifting demographics and fracturing financial structures, the phrase – applied as real-world evidence (RWE) – can provide landfall in a sea of turmoil.
Companies are now recruiting high-level executives to lead well-resourced RWE teams; it has gone from a sub-specialty wedged into spare office space down unfashionable corridors to an integral part of the business and seats at the top table.
Using RWE – derived from multiple sources across clinical, commercial and social settings – is seen as a way of improving therapeutic outcomes and opening up vistas of new pricing and reimbursement structures.
Data washes around healthcare systems but often evaporates because its power has been difficult to identify and harness.
We live in data-rich times. It streams from electronic health records (EHR), claims databases, registries and lifestyle software so it makes sense to use it. But its collection and context is varied with anything from idiosyncratic hospital coding to machine and human input error introducing bias into the formula.
A need for caution was highlighted by the US Food and Drug Administration (FDA) in a debate primer published in the New England Journal of Medicine in December that stated: ‘If we are to realise the full promise of such evidence, we must be clear about what it is and how it can be used most effectively, and we must have appropriate expectations about what it can tell us.’
The hope is that balanced data will tell us an awful lot. Understanding why some therapies don’t work for some patients, despite indications from randomised clinical trials (RCT), could lead to more precise treatment, a drastic reduction in medical waste and improved outcomes.
Knowing why patients fall off prescribed treatment pathways will allow industry to work with healthcare systems to ensure the real benefits of drugs reach the public, says Hanno Ronte, a life science partner and RWE specialist at analysts Deloitte.
“The big benefit for industry is that RWE allows you to look at potentially very different commercial engagement models which could range from indication and outcomes-based pricing to population and pathway-based pricing,” he adds. “They all need a good dose of RWE. It is a case of supply and demand. The supply is that healthcare systems are recognising that their electronic data records are very valuable and can be used not only to improve service delivery but also as a valuable asset in partnerships with pharma. And the demand is that healthcare systems and industry are trying to find better ways of working together and solving the affordability challenge.”
Professor Martin Cowie, honorary consultant cardiologist at the Royal Brompton and Harefield NHS Foundation Trust, wants to see RWE factored into treatment equations and believes the sole reliance on RCTs betrays the wealth of clinical experience that can be used to finesse and target therapy delivery.
He stiffens his advocacy with a quote from the pioneer of modern RCT, the epidemiologist Arthur Bradford Hill who stated: “At its best a trial shows what can be accomplished with a medicine under careful observation and certain restricted conditions. The same results will not invariably or necessarily be observed when the medicine passes into general use.”
Cowie adds that RWE should be discussed with patients when coming to a shared decision about their treatment.
The ROADMAP project is interrogating RWE across Europe
Michael Seewald, global head of real world evidence at Novartis, which has established a Centre of Excellence, believes it has multiple uses.
“First and foremost RWE has a key role to play in post-approval settings,” he says. “Regulators are looking for ways to understand benefit-risk. Payers are increasingly challenging the value of new health technologies. RWE can help to demonstrate value vs standard of care. In addition, RWE is uniquely helpful to highlight how care is provided in real life, ie how ill patients are, which medi-cations are provided to them, what the burden of disease is today.”
“It is increasingly powerful to characterise patient populations and their outcomes,” he adds.
“Clinicians recognise the value of disease registries and databases, as they supplement their strong clinical knowledge with data from routine clinical practice across various geographies. We do see significant value in RWD informing the design of clinical trials, portfolio management of R&D projects and also helping to improve the operational aspects of clinical development.”
Novartis has used RWE extensively across its oncology portfolio and Seewald feels that improved data collection should help industry become stronger and improve outcomes for patients.
Dr Linda Landells, associate director at NICE, although welcoming the use of ‘other types of evidence’ applies the brake slightly by underscoring RCT as the prime essence of its decision-making.
“There should be no concerns that NICE’s rigour will be dampened. Randomised clinical trials typically underpin the decisions we make at NICE about drug treatments. That will never change,” she states.
“No matter the type of evidence, we apply the same scrutiny to make sure the information is robust, of good quality and fit for purpose. Continued debate on generating high-quality evidence is of course welcome but it’s clear that real-world data will play an increasingly important role in how drugs are assessed in the future.
“Industry, academia and the public sector will all have to work together to make this a real priority.”
Barely a month goes by without industry being exhorted to shape-shift through contorting and constricting healthcare systems as the financial indicators ram home the point that the blockbuster era is over. It is hard to characterise RWE simplistically as the cavalry charging over the hill to rescue an industry in distress, but it has a big role in the future.
And the Association of the British Pharmaceutical Industry is convinced that the NHS, which has perhaps the greatest treasure trove of data, can be a global leader.
“RWE evidence is important as it can help to evaluate the safety and effectiveness of medicines outside a controlled setting, allowing treatments to be monitored across larger populations of patients and providers,” says Dr Shahid Hanif, head of health data and outcomes at the ABPI. “The use of such data has the potential to not only improve but to also accelerate the development and delivery of safe and cost-effective medicines to patients, and has been particularly beneficial for providing the evidence for accelerated access to medicines and the Cancer Drugs Fund.
“The NHS, with the right infrastructure and support, could become a global leader in how to use real-world evidence and clinical data. By involving patients, industry, regulators and government, we need to develop clear requirements to ensure the correct evidence is collated for evaluation. With these effective measures and guidelines in place, the UK could be the best place in the world for the research and development of new, innovative medicines, benefiting the UK economy, the NHS and, most importantly, patients.”
With the Brexit wounds still fresh, the NHS will have to find a way to collaborate across Europe to make the best of its data mine.
Catherine Reed, of global patient outcomes and real world evidence at the Lilly Research Centre UK, views Europe as a key player in developing RWE. Lilly, which has spent around $3bn on researching Alzheimer’s treatment, believes its public-private partnership in an Innovative Medicines Initiative project, led by the University of Oxford, could unlock key factors in combatting the condition. The ROADMAP project is interrogating RWE across Europe with the aim of creating a better ethical, legal and social framework.
One of its aims is to ‘identify RWE in Alzheimer’s to better inform the future regulatory environment – for regulators on matters of efficacy and safety and medicines; for medicines manufacturers on building a sustainable payer environment; and for providers on cost-effectiveness’.
Reed sums up the potential: “With the help of real-world evidence, the entire population becomes the decision-making laboratory.”
There is a great deal of hard graft and cooperation needed before RWE can life up to its game-changer tag. Seewald views it as a ‘unique opportunity’ but recognises that greater collaboration, ‘clean’ data collection and enhanced governance need to be established, while privacy issues are also dealt with, across a broad and complex landscape.
“It is worth it,” adds Ronte. “I believe using this sort of data is the only way we are going to solve the affordability and patient-need problem. It is worth trying to find a way of working with data more constructively and consistently. We will only continue to collect more and more data.”