A conversation with Shawn Li, Bristol-Myers Squibb; Danny Wiederkehr, Pfizer; and Soeren Mattke, University of Southern California
This is part 2 of a two-part roundtable Q&A on real-world evidence (RWE) in the 21st century. (Read part 1.) In this installment, our experts discuss how RWE is utilized, why real-world data (RWD) analyses are getting more attention, and what the recent attention means for the future of medical practice and drug development. RWD analyses are utilized to generate insights about a medicine’s effectiveness, safety, and associated costs. This data may help explore additional research questions, complement clinical trial findings, and fill knowledge gaps related to how a medication is used in real-world medical settings.
Our expert participants are:
Why and how are pharmaceutical companies focusing on real-world data (RWD) analyses?
Danny Wiederkehr, Pfizer: There is a plethora of anonymized patient information available to researchers in the form of electronic health records (EHRs), claims databases, and more. Thanks to the accessibility of data sources, RWD analyses can be especially time- and resource-efficient. When you consider medications and a patient’s full care experience, the information healthcare professionals are relying on, such as treatment guidelines or pivotal trials, may be years or even decades old.
RWD analyses allow us to make use of data that is available now and analyze it to form insights on how patients are responding to a drug in the real world. RWD findings can be obtained and shared with providers, payers, and others in the healthcare system to inform patient care.
It’s very important to note that, in some cases, conducting a randomized clinical trial (RCT) is not feasible due to ethical concerns. This is particularly true in highly comorbid patient populations or when studying patients in severe stages of disease progression, where researchers and physicians may be uncomfortable using placebo. RWD allows us to analyze historical data from patients who are similar and to make informed inferences in lieu of data from a population that can’t be studied.
Shawn Li, BMS: Another important investigative opportunity that RWE has provided to pharmaceutical companies like the BMS-Pfizer Alliance is the ability to learn more broadly about the patient experience and gaps in care.
Healthcare claims data is well suited for real-world analyses in the cardiovascular space, where outcomes of interest, such as heart attack or stroke, typically lead to hospitalization. For other therapeutic areas, a researcher may select a different data source, such as EHRs, based on the research question they are looking to address.
Why is RWE getting so much attention now?
Li: Interestingly, though RWD analyses are not without limitations, this type of data is not new, and has been used by many healthcare decision makers for decades. In particular, RWE has been used by payers to decide formulary preferences and associated coverage.
Since this kind of data is from clinical information reported and collected in medical settings, such as hospitals, primary care facilities, clinics, or emergency rooms, it provides useful information that complements clinical trial findings and may fill knowledge gaps related to how a medication is used in real-world medical settings. This is key to better understanding a treatment and improving overall patient care.
Wiederkehr: Another point I would like to add is that regulatory organizations, like the FDA, have long used RWE in addition to the robust data gathered in clinical trials to “maximize [a medicine’s] benefits and minimize any potential risks” by monitoring drugs post-approval as a method to flag or remove any that appear to be unsafe, thereby identifying unforeseen risks. Additionally, the European Medicines Agency (EMA) has recognized there are important questions not addressed through RCTs that can be investigated via RWD analyses.
In fact, the FDA is now working to identify additional areas where RWE could support statements of efficacy based on RCTs. As part of the 21st Century Cures Act, the FDA is developing a program to assess the use of RWD in support of approvals for new indications for previously approved drugs.
Soeren Mattke, USC: There are more data sources available now than before. Researchers used to be very protective of their data, collecting it but never sharing with the larger scientific community. Now there is more communication between the pharmaceutical industry, hospitals, and insurance companies, especially regarding sharing anonymized patient claims and other data. There is a growing realization that, with the appropriate safeguards, much can be learned from data sharing. To me, RWD is important in helping us continue to explore outcomes of treatments and identifying unmet patient needs.
What do you see in terms of the future of RWE and its role in drug development?
Wiederkehr: To me, the future of RWD is bright. In recent years, we’ve seen advancements in technology and policy that contribute to greater information sharing, such as the HITECH Act of 2009, which promotes the collection and exchange of electronic-protected health information between doctors, hospitals, and other entities. This has certainly made the data sources available to us more robust and the institutions populating them more collaborative.
In fact, in a statement to the National Academy of Sciences last year, FDA Commissioner Dr. Scott Gottlieb announced the agency’s commitment to use RWE to close the evidence gap between the information used by the agency to make decisions and the information used by other healthcare stakeholders. The FDA is now in the early stages of understanding how RWE can be used in the context of regulatory submissions and is currently supporting the first randomized clinical study conducted in a real-world setting.
Li: Outside of how regulatory authorities may refer to RWE in their decision process, there is also a space for drug developers to use RWE across the lifecycle to supplement evidence generation and inform decision-making. For example, RWD studies can be conducted to strategically align with corresponding stages of product development. These stages might include target selection, lead generation, lead optimization, proof of mechanism and principle, development for launch, and full launch.
Mattke: I think there is a growing realization that RWE could be used for positive regulatory decisions. Clinical trials may have limited generalizability to an all-comers population, because of the selection criteria. Researchers can use RWD to study the effectiveness and safety of a drug in populations and indications that were not covered in clinical trials by looking at off-label use. While pharmaceutical companies cannot use or communicate such findings, it is possible that regulatory bodies may use RWE for label enhancements and similar decisions in the future.
I am a big fan of using RWE for analysis in population-level diseases because even the slightest change in care for highly prevalent conditions will have a big effect on outcomes.