By Shawn M. Schmitt
Communications Specialist, Enzyme
Call it “proving by doing”: A former Food and Drug Administration (FDA) official who led the effort to draft the US agency’s very first guidance document on real-world data says it’s imperative that pharmaceutical and medical device manufacturers shake off concerns about using RWD to support new product submissions so they can minimize the number of costly, time-consuming clinical trials conducted in their respective industries.
“For any drug or device development project, you need to manage your risk,” says Ben Eloff, Senior Advisor for Maryland-based consulting firm Healthcare Innovation Catalysts. “These types of projects are very expensive propositions, very risky propositions, and when you have real-world evidence [RWE], a new trial design, a new way of generating data, then that adds risk. And if a company sees that maybe it’s a little bit more expensive to go down the tried-and-true path but it’s less risky, they’re going to take that that path almost every time. So there needs to be more demonstrations that using RWD systems for clinical trials can be done, as well as better education and knowledge on how to do the mechanics of these studies.”
After all, he says, “I have no doubt in my mind whatsoever, and I will take this to the grave, that appropriately controlled, appropriately qualified, fit-for-purpose, real-world data is every bit as good – and sometimes even better – than the clinical trial data that you would get through a standalone system.”
To pooh-pooh the use of real-world data is to assume that real-world medical professionals are not accurately or wholly collecting data on the patients they treat.
“I have a friend who has said, ‘I’m a doctor, I use electronic health records every single day to make life-and-death decisions on these patients in front of me. So then why, when I go to a clinical trial, are those data not good enough?’” Eloff said. “I reflect on that every time I think about the topic of RWD. It’s not like doctors are entering the wrong data. I think we need to learn how to bring the quality – and the right checks and the right nomenclature – into the health records we’re using so we don’t have to have these two separate systems.”
Eloff suggests that the pharma and MedTech industries “harmonize by doing” to bring those systems together.
“You don’t work out all of these things on a blank sheet of paper and try to find all the problems that way because you’re not going to,” he said. “You do these trials, you walk down this road together, and in that process, you find the issues – the things that need to be corrected and tweaked moving forward – and you do it in such a way that that you’re open and collaborative between the academic circles, the regulated industry, and the regulators, because that that back-and-forth is critical to achieving public health goals.”
And making sure that manufacturers, regulators, and other stakeholders are singing from the same song sheet when it comes to definitions around the use of RWD is of the utmost importance if such data is to supplant the use of standalone studies for drugs, devices, and in vitro diagnostics (IVDs) in the long term. (Related: “Embrace Real-World Evidence To Avoid Costly Prospective Randomized Trials That can ‘Strangle Innovation,’ RWE Expert Says” – Enzyme, Nov. 15, 2024.)
“One of the big issues that real-world evidence has is a nomenclature issue,” Eloff said, noting that many industry and scholarly articles on the topic present a false dichotomy between randomized trials and real-world data. “Real-world data collection is different than an observational study design. Yet I would say the vast majority of people I’ve talked to equate those two inherently. Even people I’ve had longstanding conversations and relationships with over many years still equate real-world data collection and real-world evidence with an observational trial – observational being, ‘Oh, you came in for care, and I’m just going to collect data on you and reuse it,’ rather than an interventional trial, which is, ‘Here is a trial protocol. I’m going to treat you this way. I’m going to collect these data on you and follow up with you,’ and use real-world systems for collecting those data.”
“Observational,” “interventional,” and “randomized” are all terms that describe the experimental design of a study. Each of these designs can be accomplished using a complex, expensive, cumbersome standalone data collection system or RWD, which is already being collected anyway. An example of this is the SAFE-PCI for Women trial that used an existing registry to complete a prospective randomized study of roughly 1,800 women. The total cost of the trial was half the projected estimate and went from start to finish in less than a year. The site personnel were the same clinical staff who regularly care for patients, and they entered data into the same forms that they use every day.
Resources to Learn More About RWD, RWE
Eloff held a few different titles during his more than 13 years at the FDA, including Deputy Director for the Division of Epidemiology within the agency’s Center for Devices and Radiological Health (CDRH). While in that position he also served as team leader for “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,” a guidance that was finalized in 2017.
“For those looking to adhere to US regulations, the FDA has done a good job of putting out a whole host of guidances and draft guidances. Those are clearly required reading,” he said when asked if there were documents other than the 2017 agency guidance that manufacturers should keep a sharp eye on when it comes to RWD and RWE.
“The challenge is that real-world evidence has become a bit of a buzzword in circles, and so there’s a lot of noise in the world, and so many organizations are looking to capitalize on the excitement or perceived excitement,” Eloff said. “But the International Society for Pharmacoepidemiology, ISPE, is always a trusted source of information and practice. The epidemiologists have really taken on real-world evidence. Epidemiology has been rooted in in the science of the real world for decades, if not centuries.
“And so continuing along those lines, epidemiologists have really been helping push the science forward. So paying attention to that is important,” he added. “In terms of one treatise that really lays it all out for you, I think anyone would have difficulty citing one paper or one resource. I do think that the 2018 FDA framework for its Real-World Evidence Program is very good, although it only applies to drugs.”
Advice for a Smoother RWE Experience
Because collecting and using RWD can be tricky for even the most experienced drug or device company, Eloff offered some advice to help ensure a smoother process.
“Remember that there has already been a lot of work done on whatever variable it is that you’re trying to ascertain, and don’t approach it as being real world. Rather, approach it as, ‘I’m going to have a doctor in medical practice collect this data. How do I make that happen?’” he said.
“Because when you say ‘real world,’ you’re making it scary, something different,” Eloff said. “So, what does ‘real world’ actually mean? It means that rather than having a specialized clinical trial person, and all the site monitors and all the expense that goes along with that, you’re going to have the person at a point of care enter data. So, how do you make that happen in a reliable way? And the answer to that is to use data systems that already collect those data.”
Eloff also urges manufacturers to try new things when it comes to using real-world data.
“It’s the scientists at the FDA who are making these decisions regarding product submissions, and the scientists at the FDA are going to pay attention to good science. And really, everybody wants the same thing, which is the best, safest, most effective therapies available,” he said. “The worst thing that can happen is to never get those therapies to the people who need them because the cost of collecting data is too high or the barriers to collecting data are too high.”
