Real-World Data Playing a Bigger Role in Drug Development

Changes in the way data are being collected are on track to revolutionize the use of real-world data in drug approvals, Janet Woodcock MD, the longtime director of the FDA’s Center for Drug Evaluation and Research, said here.
“Traditional drug development programs … don’t usually get much insight into who to use a drug in and who not to use a drug in,” Woodcock said Thursday at an event on the future of health data sponsored by Datavant, a company that helps healthcare systems with patient identification. “Are there ways we can capture and utilize the data collected … to make the clinical trial enterprise more effective and efficient?”
The widespread use of electronic health records has drastically improved the availability of health data, she said. With paper charts, individual physicians “had to do archaeological expeditions — literally — to find out what was going on. The same is true of FDA — we used to get tractor-trailers’ worth of paper, literally [to approve drugs] … Now we get data sets that are standardized.” The other big factor “is the digital revolution in general — people have wearables, a lot of people have iPhones, we have telehealth that’s developing. All these things are coming together to provide rich data sources that we can turn into evidence. Our task is to take all the data out there and turn it into something that’s actionable.”
Real-World Data in Use
FDA already has approved numerous supplements and many drugs based on real-world evidence, Woodcock noted. “These are usually for rare conditions, such as male breast cancer, which doesn’t happen very often but is just as devastating as any other cancer. We were able to use evidence generated from use to add that indication to the label.” Using this type of evidence plays into “the long-term vision, articulated quite some time ago by the [National Academies of Sciences, Engineering, and Medicine] as the ‘learning healthcare system’ — that we’re able to make all the information we collect actionable, to assimilate that learning from treating patients and rapidly transform it back into best practices … We’re very, very far from that, but that’s the long-term vision.”
“In the shorter term, what we’re going to see is in terms of drug development and the intervention space and the best practices of delivering healthcare,” she continued. “We’re already generating lots of insights about what’s the best way to do this or that … That will continue to grow.” In addition, data gleaned from wearables and other new technologies will become part of healthcare delivery.

Janet Woodcock, MD, FDA Center for Drug Evaluation and Research (Photo by Joyce Frieden)

However, as both the industry and regulators know, “the data out there are not necessarily fit for this purpose right now,” said Woodcock. Take for example, the medical chart of a cancer patient. “What does it say in the chart about cancer? Do you have the right cancer written down? Sometimes, the answer is no. Are the biomarkers in there? Are they entered correctly? That’s important information for the patients … It ought to be right the first time.”
Resisting Standardization
One problem with trying to make data more actionable is that “everyone resists standardization,” she said. “Doctors, especially, want to do things their own way.” She related a story from Peter Bach, MD, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, in New York City, who wanted to have lymphoma care and treatment standardized, so researchers could compare outcomes from different treatments. But some physicians documented their cases differently than the others, so he asked them why and one of them replied, “I don’t agree with the consensus definition of stages of lymphoma. I have my own stages.”
“We need to sell people on the return of that evidence — that if you put something down in a standard way, you’ll get something back,” Woodcock said. However, “it’s an uphill battle. There is much discussion in healthcare circles about what the electronic record is doing to clinicians and to the doctor-patient relationship. It doesn’t have to be that way. That can be fixed, but we’re really going to have to focus on that.”
One problem that crops up with real-world data is that it’s hard to screen out the confounders. “But something we’re exploring is, can you randomize people in your practice and collect real-world outcomes data … without a very elaborate clinical trial apparatus, and can you still get a valid result that’s actionable?” she said.
“We’re collaborating with a lot of groups trying to sort this out — different groups are trying to raise the reliability of that [observational] evidence … Where randomized clinical trials [RCTs] are ongoing, we’re doing a companion observational study, and we’ll see what the results are. We hope to have 20 retrospective ones done by next year, and seven prospective ones. Of course, the real-world study will get done a lot quicker than the RCT … but it will be very interesting to see how they compare and what kind of answers they give.”
Privacy Tradeoffs
The privacy tradeoffs involved in collecting data also are important to think about, said former FDA Commissioner Robert Califf, MD. “In what circumstances do we trade off privacy for the benefit of getting better healthcare? Where are we when health systems advertise the nice doctor in the white coat to cure your disease, when for the most part the doctor is guessing? The guesses are not uneducated guesses, but the fact is whenever we do prospective studies, we find out we’re wrong about half the time, but don’t know which half we’re wrong [or right] about.” For example, take the recent red meat controversy. “Is it OK to eat red meat or not? The data are contradictory because good studies haven’t been done.”

Robert Califf, MD, Duke University (Photo by Joyce Frieden)

The use of aspirin to prevent heart attacks is another example, added Califf, who will soon be leaving his position as professor of cardiology at Duke University to work for the Alphabet health subsidiary Verily Life Sciences. Although aspirin has been shown to be effective for secondary prevention, “it’s always bothered me that we don’t know the right dose of aspirin,” he said. “Now we have enrolled over 17,000 people in a randomized trial of baby aspirin versus full-strength aspirin, and we’ll soon know the answer. But this is 140 years after aspirin first went on the market … It’s possible to know a lot more than we know if we just have the discipline to admit uncertainty.”
https://www.medpagetoday.com/publichealthpolicy/fdageneral/82711