Getting Ready for the Use of Real-World Evidence

Can the data sitting in electronic health records (EHRs), claims databases, or even your Fitbit be harnessed to bring down the price of drugs?

A line that straightforward would be a lot to ask. However, thanks to a law Congress passed in 2016, FDA has launched a process that will give real-world data (RWD) generated outside clinical trials more importance than it’s had in the past—with implications for payers, drug companies, and most of all, patients.

Last week, the National Pharmaceutical Council (NPC) hosted a webinar, “Let’s Get Real: How Will the FDA Framework for Real-World Evidence Affect You?” which answered questions about the December 2018 document that outlined the regulatory philosophy, process, and timetable for bringing new data sources into use under the 21st Century Cures Act. The law’s intent is clear: using real-world evidence (RWE) has the potential to make drug development faster and more efficient, and potentially less expensive than it would be otherwise. And FDA responded with a framework that calls for not a single guidance but several:

• FDA will look at the possible role of observational studies “in contributing to evidence of product effectiveness,” and create guidance on how these studies might support regulatory decisions.
• FDA plans to issue guidance on how to properly “assess the reliability and relevance of RWD from medical claims and EHRs used to generate RWE regarding drug product effectiveness.”
• FDA plans a guidance on “potential gaps in RWD sources” and how to address them.
• FDA will create guidance on how to design pragmatic trials that can lead to regulatory decisions.
• FDA will finalize a guidance on use of electronic signatures.

The NPC panel was moderated by Jennifer Graff, PharmD, vice president for Comparative Effectiveness Research at NPC, and featured Eleanor Perfetto, PhD, MS, executive vice president for Strategic Initiatives at the National Health Council, which represents a coalition of advocacy groups for different disease states; Tricia Lee Wilkins, PharmD, MS, PhD, director of Pharmacy Affairs for the Academy of Managed Care Pharmacy; and Brande Yaist, MHS, senior director, Center of Expertise in Global Patient Outcomes and Real-World Evidence for Eli Lilly and Company.

Graff explained that RWE is already used to monitor safety through FDA’s Sentinel Initiative; it has been issued in a limited way to evaluate rare diseases or to meet post-marketing requirements. Payers already use RWE alongside clinical trial data for decision-making.

“When 21st Century Cures first came out, there was much excitement about being able to use real-world evidence,” Graff said, but she pointed out that not everyone thinks that the speed that RWE could offer is a good idea. “How should it be used? How could it be used? And what are the safeguards that we need to ensure that it is being used appropriately? FDA has taken that work very seriously.”

FDA has created a defined framework for incorporating RWE: are the RWD fit for use? Does the trial generating RWE answer a regulatory question? And does the study meet regulatory requirements?

A key change, Graff explained, appear that FDA will consider both healthcare system data and patient-generated data sources, such as those created by mobile health sources. But in answering critics, “Context and quality will be of primary interest,” she said.

Another key is that the randomized clinical trial will still be the standard for initial approval, with RWE used to add new populations, doses, or indications, and comparative effectiveness information. Of note, Perfetto said when National Health Council did research of public perspectives on use of RWE, most people needed an explanation of what it was. But once they heard a description, most agreed that use of RWE was appropriate only after a drug had been approved, and it was fine to use for additional indications.

Clinicians, she said, must be “champions” of RWE, and must make it clear to patients what the limits of its use are. Patients are concerned about privacy and consider themselves the “authentic” sources of real data.

Yaist said that the pharmaceutical industry shares many of the concerns raised in FDA’s framework: greater use and acceptance of RWE will depend on development of standards for data, including reliability standards for EHR data, transparency of study designs, and the creation of “causal inference of treatment effectiveness in observational studies.”

Wilkins said that FDA’s framework could lead to additional information for AMCP to evaluate the reliability of real-world evidence. Right now, recent research show that while RWE informs decisions by pharmacy and therapeutics committees, only a small fraction of these studies leads to decisions by these panels.

Are there factors that make RWE worthy of greater consideration? Graff, in an interview with The American Journal of Managed Care^®, noted that nearly a decade has passed since the Health Information Technology for Economic and Clinical Health Act, was enacted in February 2009, which spurred more than $25 billion in investment into health information technology. “The data are finally starting to mature,” she said.

RWE will also allow the scientific community to find data sources from populations historically left out of clinical trials, Graff said.

What are the roadblocks to using RWE? Have recent reports about hacking of healthcare systems and Facebook privacy incidents deterred patients from sharing data? Graff said patients do have plenty of questions, sand she cited the need to answer questions about the trustworthiness of data sources and the use decentralized networks. The lessons learned through the use of the FDA Sentinel system will be instructive, she said.

And patient-collected data will offer lessons, too. The group Patients Like Me is generating data in certain rare conditions that is trimming time and cost from the process of finding patients with conditions like ALS.

Patients, Graff said, have a common sense view of privacy issues. “Overwhelming, 80% to 90% of patients are willing to share their data with the hope that it might inform the care of their family members. They want to know who and where it is going to. That’s where the privacy nuances are going,” she said.