BETHESDA, Md. -- Real-world evidence (RWE) and real-world data (RWD) are already being used in a variety of ways to improve patient care and search for disease cures, participants said at a workshop here sponsored by the FDA and the American Association for Cancer Research.
Policymakers agree that RWE has the potential to meet the burden of evidence for regulatory considerations and may help to speed up drug approval. For instance, in March 2018 the FDA fast-tracked approval in the U.S. of blinatumomab (Blincyto), a second-line treatment for Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia, came on the heels of a simple weighted RWD analysis, explained Michael Kelsh, MD, MPH, director of observational research at Amgen. The analysis found that adult patients with the rare disease who had enrolled in the single-arm phase III clinical trial of blinatumomab and a case study follow-up went into complete remission.
The 21st Century Cures Act, enacted in December 2016, made modernizing clinical trial designs and the use of RWE a legislative priority within the nation's most experienced and sophisticated research networks. It defined "real-world evidence" as "data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials." The workshop, which was held on July 19th, aimed to increase stakeholder understanding of how RWD relates to regulatory decision-making and delivery of healthcare data collected outside of clinical research settings. These include electronic health record data, billing data, patient surveys, clinical trials, and observational cohort studies linked to outcomes in real-world settings.
FDA will collaborate with stakeholders in the adoption of development standards and implementation strategies. The agency also is developing guidance on how patient data captured at the point of care can be used for clinical trial design and prospective research studies. The health care community is using these data to support coverage decisions and develop decision support tools for use in clinical practice. A new regulation will require randomized clinical trials to draw on real world evidence and observational studies to encourage sharing of lessons learned about best practices in differentiating RWE research from conceptualization and design analysis.
RWD can quantify outcomes and establish an unmet medical need to support regulatory and payer submissions, said William Capra, PhD, Global Head of Real World Data-Science Oncology at Genentech. In March 2019, the FDA granted the company's atezolizumab (Tecentriq) accelerated approval for patients with PD-L1-positive, metastatic triple-negative breast cancer after the IMpassion 132 phase III double-blinded, randomized clinical trial produced definitive evidence of its efficacy.
An interim analysis at 18 months reported no statistically significant overall survival benefit, but analysis of patients who tested positive for PDL1 expression confirmed a clinically meaningful OS improvement of 7 months versus placebo and nab-paclitaxel -- a median of 25 months versus 18 months. More than half of the patients in the experimental arm who were PD-L1 positive were alive at 2 year versus 37% of controls, Capra said.
Observational studies are an important part of RWD, and they can help assess enrollment criteria and trial feasibility, and compare outcomes to determine where guidance is needed, noted Jacqueline Corrigan-Curay, MD, JD, director of the Office of Medical Policy at FDA's Center for Drug Evaluation and Research. For example, researchers are now comparing observational data and on-target results for telmisartan (Micardis) and other agents for hypertension and atrial fibrillation, she said.
The National Cancer Institute's (NCI) Genomic Data Commons (GDC) is another organization that uses RWD, said Robert Grossman, PhD, a computer scientist and bioinformatician at the University of Chicago. Launched in 2016, GDC provides the cancer research community with a unified data repository that enables data sharing across cancer genomic studies in support of precision medicine. For instance, GDC uses interactive tools to explore kidney cancer data and collect cohort information from demonstration projects and other pipelines. The 50 projects and 34,000 cases it manages will likely triple by 2020. Medical research centers supply genomic, longitudinal, and associated clinical treatment and response data to the research community.
NCI also has an ongoing data collaboration with Flatiron Health; the two organizations are using clinical and genomic evidence from patient care to gain clinically meaningful insights for advancing oncology research and informing clinical guidelines, said Neal Meropol, Flatiron's vice president and a research oncologist. The continuously updated database includes patient outcomes from Flatiron's oncology clinics, and it links to comprehensive genomic profiling results. The data may not capture date of death, so obituaries enhance the death data.
Another use of RWD, next-generation sequencing, can predict the tumor of origin in patients who present with multiple malignancies, and it is being used to report on 6-month progression-free survival among patients who share the same phenotypes, said Gary Palmer, MD, JD, chief medical officer of Tempus. Tempus uses treatment incidence and response rates to identify beneficial therapeutic pathways for each patient and helps to enroll patients in its time trial network program for trial matching.
In addition, RWE also facilitates the approval of off-label drugs, predicts real-world effectiveness, identifies potential sites and investigators for clinical trials, and makes real world data systems accessible to researchers, said Elad Sharon, MD, MPH, a senior investigator at the National Cancer Institute.
Andrea Coravos, CEO of Elektra Labs and digital rights advocate, said FDA is considering the use of wearable phone apps for collecting data relevant to the clinical care of cancer patients.
Some meeting participants raised ethics concerns about patient data being used by for-profit companies. Oliver Bogler, PhD, chief operating officer of the ECHO Institute, and a cancer survivor, is troubled about commercialization and wants patients to own their personal data, as they do in India. "You're giving data away and if phenotypes are used, they expose the next 20 generations of your family to the loss of privacy," he said.