Real-World Revolution Part 2

Changing mindsets in clinical research

According to Takeda's Thy Do, the secret lies in changing our mindset towards clinical trials. “Rather than asking ‘Will this treatment work in the real world?’ we ask ‘Does this treatment work in a well-defined population?’. Pragmatic trials involve a complete change in mindset; the traditional clinical trialist thinking about stringent enrollment criteria is trying to homogenize the patient population and shift the population into a higher risk area so it’s easier to see a treatment effect. When you’re thinking about a pragmatic clinical trial, you erase all that; you say, ‘I’m going to treat patients at this hospital with treatment A and at this hospital in a neighboring city with treatment B’ and you let the physicians do what they want. At the end of the day, you see what effect A and B have had.”

Yet, such trials come with a lot of variables, he says. “How do patients differ between hospitals A and B? How did the physicians differ? Are there differences in formulary access? It adds many layers of complexity when you’re thinking about the design and you make a lot of assumptions. It’s a completely opposite way of thinking about trials – moving from homogenous to ‘anything goes’.”

Specific features of the pragmatic trial concept can be used to reduce the cost of a RCT, says Mats Sundgren, Director and Principal Scientist at AstraZeneca. These features can include registries and EHR-driven data collection. “Pragmatic trials offer faster recruitment times and the opportunity to reduce costs related to source data verification, which are a heavy burden in RCT currently. They also offer engagement and enhanced collaboration with academic institutes and hospitals.”

Academic and clinical research organizations are using such trials with great success, he says, pointing to the TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction) study in Scandinavia. “They enrolled 5,000 patients and the incremental cost for trial execution was approximately US$ 300,000 or $50 per patient,” he says. “This points the way to an entirely new way of performing randomized clinical trials rapidly and inexpensively.”

By using RWE to inform clinical trial design and recruitment we’re seeing a 30% efficiency gain. It’s very substantial.

The concept of a ‘pragmatic trial’ is not yet clearly defined, he says, with companies employing both full-blown real-world-data powered clinical trials as well as using some pragmatic elements by incorporating EHR and disease registries to inform clinical trial design. The latter is the way forward because “this offers the opportunity to conduct research faster and cheaper than before; the status quo isn’t sustainable. If the prospect of using RWE wasn’t on people’s radar before, then it should be. Given the success of pragmatic trials to date, within five years, we’ll see a substantial portion of trials will be pragmatic.”



Opportunities across the lifecycle

Looking across the industry, companies have typically focused RWE efforts on demonstrating value in market access but there are many other opportunities, says Ben Hughes, Vice President and head of technology and innovation, Real World Insights, at QuintilesIMS. “It’s not just about evidence, it’s about finding ways to continuously develop data and insight around the use of a product over its lifecycle. It’s not just about making formal claims around the efficacy and comparative effectiveness of the product or how it’s being used, but informing a series of decisions with the organization on how to use resources better.”

By systematically connecting different datasets, companies can deepen their understanding of patient journeys and market dynamics, he says. “Marketing and sales efforts can be transformed by focusing on very specific points along the patient journey or in the physician decision-making process, or by gaining a deeper understanding of latent sales potential. There are opportunities to improve RCT design with RWE, accelerating recruitment to enabling initial dossier submission and reducing the number of iterations to final decision. Products get to market faster, so it goes all the way along the lifecycle from development to late-stage commercial,” says Hughes.

With the most successful companies realizing substantial value across the product lifecycle, RWE leaders are poised to capture sustained value. “By way of example, by using RWE to inform clinical trial design and recruitment we’re seeing a 30% efficiency gain. It’s very substantial.”

Data sharing

In our modern world, data is the new capital; RWD and RWE will play a crucial role in providing additional insights for healthcare organizations from providers to payers to pharma companies. However, to make best use of these data they must be available for research and analysis.

Privacy issues are a major hurdle. Speaking generally, the more broadly that data is made available, the more insights and innovation can be derived. For example, once National Oceanic and Atmospheric Administration made US weather data available, others started to leverage it, developing

weather apps, insurance and other tools. “The case is more difficult in healthcare,” says Peter Speyer, Global Head of Real World Solutions at Novartis. “Health data need to be made accessible while protecting privacy and confidentiality, but once you start removing dates and geographical identifiers to anonymize the data, usability and the ability to derive insights quickly goes down. The better we can share information while protecting the interests of patients and companies, for example, via statistical de-identification or distributed analysis, the faster we will advance.”


Takeda’s Do is a strong advocate of data sharing. “In many European countries, they’re starting to clamp down on privacy laws. What would be great is if companies operating across similar therapeutic areas could pool resources and build open-access data repositories. How companies use these shared data could still be confidential, but the data collection would be more transparent and efficient.”

There are many challenges to address before the potential of RWE can be realized. “In terms of data access, we need to be open about the need for real-world data – there’s an education requirement and it goes all the way up to government as well,” says Janssen’s Nigel Hughes. “If we speed things up, it would make an enormous impact. With privacy, we need to review what regulatory changes are happening in Europe and data protection legislation. We again need a healthy, honest and transparent debate. We have a lot of challenges in terms of agendas and drivers, and whether we are aligned with industry and research requirements, as well as with governments and payers. We need to develop a common language and I think that’s happening. With technology, we need better standards. We need more case studies, such as the Salford Study, to highlight the benefits and challenges of RWE.”

How do we gather data in a cost-effective way? “Pharma will progress faster if it accesses patients who already collect data about themselves and come with a rich natural history,” says Munos. “It makes a lot of sense for pharma to reach out to patient organizations; many of them are busy forming cohorts and gathering all kinds of data, genomic, physiological, behavioral and environmental, as well as outcomes. This is very helpful to identify patients most suited to specific trials. It’s also getting better as patients increasingly realize that assembling cohorts has never been easier. That’s why cohorts are getting larger.”

Some of the largest cohorts in the US include:

• 23andMe: 1.2 million people (as of Feb 2016)

• The Precision Medicine Initiative’s million-patient cohort

• Leroy Hood’s P4 Medicine cohort (100K patients)

• The Million Veteran Program

• PCORNet, which can tap into its 110 million patient network – e.g., to support the cancer moonshot

• PatientsLikeMe: over 250K patients

There is little doubt that patients are signing up but questions remain. “Where will that data be stored? How will it be secured? Who will have access to it? Who will own the IP derived from it?” asks Munos. “These are serious questions that must be addressed but none is a showstopper. Answers will be found, but it will take time. Medicine will be the winner but there will also be losers. All the expected savings are currently someone’s income. There will be delays and pushbacks. The sums of money involved are enormous. Fierce resistance can be expected, but it won’t change the outcome. This is about smarter science, breakthrough therapies, affordable drugs and healthcare, and transforming a system that most patients and policymakers see as badly broken. The will of the people will prevail. It always does. There are very interesting times ahead.”

Part 2 of a series. Read part 1 here.

Extracted from Trends in Real-World Evidence Magazine. To download, click here.

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