Real-world evidence (RWE) has emerged as a useful tool for industry and regulators in oncology—to date, the FDA has accepted submissions using real-world data (RWD) and evidence to support drug efficacy and effectiveness claims, especially in rare tumor types. It’s also been used to create comparator arms in single arm oncology trials.
But how can clinicians leverage RWE to inform their decision-making on how to best treat patients with cancer? We discussed that with Deb Schrag, M.D., M.P.H., Chief of the Division of Population Sciences and attending physician in the Gastrointestinal Oncology Center at Dana-Farber Cancer Institute, and professor of medicine at Harvard Medical School.
As both an observational researcher, whose research focuses on evaluating and improving the quality and effectiveness of cancer care delivery, and an oncologist, Dr. Schrag is uniquely positioned to address the impact of RWE in oncology clinical care. Among her top recommendations for advancing RWE is the development of standards: According to Dr. Schrag, RWE will remain a “companion contributor” to evidence packages until all RWE stakeholders embrace a common standards language.
Responses have been edited for clarity and length.
Q: Where do you see the greatest potential for RWE in cancer care?
A: I think of RWE’s potential areas of impact in three buckets: patterns of care, toxicity, and comparative effectiveness of treatment interventions.
Q: Where does RWD affect clinician decision-making today?
A: We use RWD to identify gaps in care delivery, and will continue to do so. The faster we can obtain RWD, the more readily we can create high quality data visualizations and place that data into decision makers’ hands. The better we communicate this data, the easier it will be for stakeholders to take action.
RWD also impacts how we evaluate toxicity. Immunotherapy, for example, was approved for lung cancer patients, but there was concern about using it to treat patients with autoimmune disorders. After FDA approval, RWD from patients treated with immunotherapy was cautiously reassuring, as it suggested that off-label use and scope creep did not result in any evidence of danger. However, “cautiously reassuring” is not the same as “positive compelling evidence” and “definitive benefit.” It’s evidence of a lack of irreparable acute harm.
Real-world evidence has been better at demonstrating no irreparable acute harm in off-label contexts than in showing that drugs work as well for 80-year-olds as they do for 60-year-olds. For that, you need more detailed data.
I think we’ll get there, both as statistical methodologies improve and as the ability to manipulate clinical data for these purposes expands. I’m optimistic, but also sensitive to the need for rigorous randomized controlled trials.
Q: You’ve mentioned that the field of oncology would greatly benefit from standards around data collection and quality. Which would you consider top priority?
A: We need more tools and guidelines to enable structured reporting for all oncology scans—not just for the presence of cancer, but also for the cancer’s progression. We also lack data standards to understand a drug’s clinical benefit and the patient’s progress. It’s amazing how much ambiguity exists around those fundamental questions.
The field has made some progress. Oncology researchers from Kaiser Permanente have developed a model for data standards called the Prognostic Information System, or PRISM. PRISM retrospectively evaluates endpoints from EHRs and allows us to calculate priority metrics like real-world progression-free survival, real-world response, real-world recurrence, disease-free survival, and progression-free survival.
When a radiologist interprets a mammogram, they give it a Breast Imaging Reporting and Data System (BI-RADS®) score from zero to six to indicate the likelihood of breast cancer detected. Though it’s not a perfect system, it’s a helpful standard: a mammogram with a BI-RADS of 1 indicates no evidence of cancer (a zero often means there was an error with the test), and a BI-RADS of six means the patient has a confirmed breast cancer diagnosis. We now have Prostate Imaging Reporting and Data System (PI-RADS®) for prostate cancer scans, as well, which operates on a similar one-to-five evaluation system.
Q: How do you envision the future of RWD use in clinical care?
A: We’re in early days here, but we work with the data we have. We may tell an 85-year-old patient that a clinical trial has shown a drug works well in 60-year-old patients. Or, we explain we have a lot of data for patients treated with a drug, but it’s unclear how this treatment will work when combined with their bad rheumatoid arthritis.
Patient care remains a combination of common sense and good principles of clinical medicine.
The real-world data sources available to physicians have certainly evolved over the years. Now, we can look at the data to identify patients with a specific set of conditions and see whether particular drugs work for them or not. However, we cannot yet go to a database and quickly identify a treatment’s benefit for a large group of people with a particular problem, and the complementary data sources clinicians use in decision-making—data in case series, anecdotal reports, and RWE—are imperfect and fraught with selection issues.
As the power of computing improves, so will the ability to quickly aggregate data sources and perform specific queries, like the effect of chemotherapy drugs in niche populations. We’ve seen just how powerful data can be in the Covid-19 pandemic—the faster we get good data, the faster we can solve problems. Having standards facilitates data sharing, which is why we are so focused on developing community consensus around standards.
We don’t yet have RWD at our fingertips to answer some of those questions, but we’re getting closer.