For years, clinical trial data was king. But as healthcare costs continue to be squeezed, there is pressure on pharmaceutical companies to actually deliver on clinical trial efficacy in the real world. It’s no small feat in the tightly controlled and “biased” environment of randomised controlled trials. This is where a growing plethora of real-world effectiveness data comes in.
From electronic health records to medical claims information, real-world data (RWD) is increasingly being used to supplement the data generated by clinical trials. Just in September, the US Food and Drug Administration released guidance as part of a framework for evaluating real-world evidence to support the approval of a new indication for an already-approved drug. This comes as more pharma companies include RWD in their regulatory applications.
But it’s not just regulatory applications where RWD can have an impact. As companies are increasingly forced to persuade budget-holders of a drug’s cost-effectiveness to ensure post-approval market access, RWD can play a central role.
Lee Stern, VP and head of global operations of the Evidence and Access Division of Certara, says the industry is noticing the shortcomings of traditional sources of clinical trial data.
It’s a similar position with rare diseases, she says, where there are often not enough patients to even recruit into clinical trials.
On top of that, different countries have different data sets. For instance, German sickness funds, the National Cancer Registration and Analysis Service (NCRAS) run by Public Health England in the UK, and the French administrative healthcare database SNDS, which covers around 99% of the population, can be specifically analyzed to understand practice patterns, resource utilisation and outcomes.
The benefits of RWD are vast, including establishing unmet need, particularly for rare diseases, how drugs are used, how a disease develops and what the costs associated with the patient journey are. RWD can also provide a comparative analysis of outcomes and costs between different drugs for the same indication.
Ultimately, explains Stern, RWD can provide a better understanding of a disease and its progression, and the healthcare and costs around it, particularly over the long-term. That’s something payers are becoming more interested in, which makes it all the more relevant for pharma to include in reimbursement packages, she says.
Oncology is a case in point. “I think payers think that the standards of care or generic treatments or basic chemotherapies are what’s being used, but in reality, when you look at the RWD, there’s a lot of very expensive off-label drugs being used because there’s just no other option,” Stern says. “Actually, when you start to compare what a new drug could be in terms of cost to the treatment pattern that exists, which can be very expensive, I think that’s a bit of an eye opener for some payers.”
Or take, for instance, Novartis’ CAR-T therapy Kymriah, used to treat a type of lymphoma and leukaemia. In post-marketing studies, the drugmaker found that in the real world the drug not only had comparable efficacy but a better safety profile than in clinical trials. According to the data, this resulted in reduced use of medications to treat the side effects reported in clinical trials, meaning better outcomes for patients and reduced costs for the associated healthcare. Given the high costs and high competition in this drug class, any associated cost-savings is a market access plus.
It’s for these outcomes and cost-savings reasons that now puts RWD on payers’ radars, says Stern. “They’re becoming more up to speed on the types of data out there and how they can be applied to their benefit in terms of reducing uncertainty around a disease and a drug and the risk when approving products.”
Shawn Bates, Certara’s VP of US sales and business development, agrees, adding that payers increasingly want outcomes data and comparative analysis based on what is happening in the real world to help them make reimbursement decisions. “Industry really is starting to have to go in that direction, because payers have substantial influence in the market space.”
Pharma would ideally prefer a one-stop-shop data source incorporating claims, outcomes, laboratory data – the works, says Stern, “[but] what I have to tell our clients time and time again is there is no holy grail data set. If there was, you’d know of it already”. She says a generic large database can sometimes be the equivalent of looking for a needle in a haystack – trying to find the right patients. The better option is to identify the exact research question and market access issue and then design a study using the right source or even sources of data.
But that, of course, presents its own challenges. Sometimes the data just isn’t detailed enough to answer the questions pharma is asking. “I feel our pharma clients get disappointed that when they look under the hood, that data is missing,” Stern says. “I think it takes a lot of very specific understanding of what is in the data and what’s not in the data in order to be sure you’re going to answer your research question.”
Furthermore, companies should keep in mind the difference between efficacy and effectiveness when interpreting the outcomes seen in RWD – they might be quite different from those results found in the trials given the totality of the patient populations that are actually being given the product. Stern says this can be especially common in the first year of a drug’s release when it’s often being prescribed to, for example, the sickest patients. “This isn’t a function of the drug not working. It’s just a factor of the different patient populations being treated.”
She suggests one way to hedge this is to use a simulation model, combining some RWD and some clinical trial data, to estimate a range of possible outcomes on how the drug might react in the real world.
Perhaps one of the most frustrating challenges is making the RWD relevant for the particular payer pharma is targeting. In many cases, says Bates, this is at the local level. For instance, what’s the local patient population? What are the local payer needs? “If you don’t have localized real-world data specific to that payer, and you try to utilise national or global level data, then your value message will not resonate as powerfully as you might need it to with the payer.”
Sometimes, says Bates, that local data isn’t even there but using RWD that’s similar to the target patient population ensures the message is as tailored as it can be for the payer and will resonate more.
Stern gives the example of diabetes, saying that often the message highlighting unmet need will be: ‘There are 64 million people with type 2 diabetes’. But a new drug won’t solve that direct problem, she notes. “A more appropriate thing to say is: ‘There are X number of people with diabetes who have tried two therapies who remain uncontrolled and are costing the healthcare system X amount of dollars’. With that level of specificity, I can then design a RWD study to answer that unmet need… and that’s going to help my value story… I want to make it very crystal clear and not just throw all the data at the payer and see what sticks.”
This is where technology can help communicate the value. In the past, value messages were presented as simple Word or PowerPoint documents, but Stern says app-based formats are now changing how pharma can communicate with payers and other stakeholders.
With app-based formats, you can choose the audience you’re talking to and the question you want to ask, with the added ability to dig deeper into the RWD, she says. “I think these digital platforms are helping us to combine all the evidence into not just a blob of information that’s unruly but something that’s very navigational and very easy to support what you’re trying to say.”
‘’These digital engagement platforms and apps can also provide clarity and an opportunity for remote engagement, which is particularly important when reaching out to local payers who won’t necessarily have a field force representative walking them through the complex information and data.’’
In addition, there is the ability to customise and localise the data instantly with each interaction, while two-way engagement and analytics highlight what those payers find impactful. “That engagement with payers probably only occurs once or maybe twice a year and the outcomes of those limited interactions are worth millions if not hundreds of millions of dollars. Being able to clearly deliver that message but tailor it specifically to their needs and their specific patient population is what will make the engagement resonate and ultimately impact a therapy’s access.”
Communicating value in this way can be done now but, moving forward, Stern says the industry needs to consider leveraging RWD from the get-go. She believes integrated drug development – where pharma integrates RWD, market access and the payer point of view into the clinical trials process – strengthens both the drug and the value story. “If that information can be brought to the clinical team in the very early stages, then at the end of the day, we’ll have information the payers want to see; we’ll have end points that might include resource use, rehospitalisations, disease progression.” It makes communicating value for market access that much easier.
Yet, as Bates notes, many pharma companies are still missing an opportunity when it comes to targeting and impacting payers. “Less than 9% of digital and traditional marketing budgets go towards payers. It’s very small … most marketing is still targeted primarily at healthcare professionals.”
While some companies are starting to up their game, particularly those in the US and Japan, Bates says there needs to be a paradigm shift. He suggests companies triple or even increase fivefold the proportion of marketing budgets directed at payers.
RWD is the magic ingredient. The opportunity is to communicate the information in the right way.
If not, the consequences are stark, as Bates notes: “If companies can not do that effectively, a lack of access will significantly stunt a product’s utilization and as a result a manufacturer’s revenues.”
In the shifting pharma landscape, RWD is not only king – it’s becoming a game-changer.
Lee Stern is vice president and the Global Head of Consulting Operations at Certara. She is involved in all global operations out of the Certara Evidence and Access Division. In her 20+ years of experience, she has been involved in hundreds of health economic models, dossier submissions, evidence generation projects and strategic product launches. Prior to joining Certara, Lee earned a B.A. degree in Neuroscience from The University of Pennsylvania and an MS in Clinical Nutrition from New York University. After obtaining her graduate degree, Lee served as the primary nutritionist in a 28-physician practice, closely affiliated with the NYU Langone Medical Center.
Shawn Bates joined Certara in summer 2020 as vice president of US Sales & Business Development for our BaseCase stakeholder engagement platform after gaining over 20 years’ experience working across the pharmaceutical and medical device industries. Having held a variety of senior leadership positions, his expertise lies in stakeholder engagement and management in the market access and medical affairs spaces.