The Friends of Cancer Research (Friends) held a meeting in Washington, DC, to release new data and discuss the value of real-world evidence (RWE) in oncology drug development. The organization released a pre-meeting white paper on the topic titled "Considerations for Leveraging Real-World Endpoints in Oncology Drug Development."
RWE is clinical evidence on a medical product derived from data sources other than a clinical trial. These sources may include electronic health records, medical claims, registries, connected devices such as sensors, and patient-reported outcomes. RWE can contribute important insights about a medical product, capture data in a broader population, enhance diversity, and even lead to the expansion of indications on a drug's label. But, as Friends has pointed out, with RWE, traditional clinical endpoints may be difficult to obtain and evaluate, and its conditions of use have not been well-defined.
As previously reported in Oncology Times, Friends launched pilot projects to evaluate, establish, and validate a uniform definition for real-world endpoints that measure the direction and magnitude of treatment effects. Inconsistent definitions of RWE and its heterogeneity present challenges, and strategies are needed to align it across stakeholders so its full potential can be realized for the benefit of patients, the organization noted.
"Back in 2009, we said oncology is the obvious place to do this work," said keynote speaker Amy Abernethy, MD, PhD, President of Product Development and Chief Medical Officer at Verily, and former Principal Deputy Commissioner of Food and Drugs at the FDA. "I think we've come a long way in using what data sources we can leverage," but there is still a long way to go, she added.
Abernethy predicted that, in the future, data relevant to a patient will be integrated from various sources, including RWE, clinical trial data, multi-omics data, and sensor data from digital health technologies. Integration of these data will capture a longitudinal view of a cancer patient's journey, emphasizing the need for transparency about how all these data are being leveraged. She noted that what is needed is updated thinking on what data exist in the health care system, learning how to use datasets and "get it right," and recognizing "the need to continue the drumbeat of public/private partnerships" on the policy side.
At the meeting, Brittany A. McKelvey, PhD, Director of Regulatory Affairs at the Friends organization, presented data on RWE from a Friends pilot project that builds on two previous projects. This plan establishes a framework for evaluating real-world response and assessing the consistency of the measure to generate RWE. The pilot consisted of seven participating data vendors contributing 200 patients each. The patients were diagnosed with metastatic non-small cell lung cancer and were treated with a first-line platinum doublet chemotherapy regimen in the metastatic setting.
The project assessed the availability of core data components for measuring the extent and duration of real-world response, including raw images, image reports, and clinician assessments. The project also evaluated the consistency of a measure of real-world response across data sources in the aligned patient population.
Real-world response using clinician assessments was relatively consistent across all RWE sources and cohorts, with consistent trends in time-to-event endpoints. The demonstrated feasibility of response endpoints based on clinician assessment suggests that real-world response is clinically relevant and further exploration may inform drug effectiveness evaluation, McKelvey said. Getting the images themselves was difficult since they were coming from varied sources, so clinician assessment assumed major importance in this real-world response pilot.
"There's a lot of variability in this," said Lawrence Schwartz, MD, Chair of the Department of Radiology at Memorial Sloan Kettering Cancer Center. He noted the clinician assessments are valuable information since the clinician is interpreting the radiology report. He also said it would be helpful to have the images themselves so they could be more widely available from different sources if they were stored in the cloud.
RWE is still apples and oranges compared to clinical data, but using it to measure response rate is more immediate, noted Pallavi Mishra-Kalyani, PhD, Deputy Director at the FDA.
In a keynote address, Robert Califf, MD, the FDA Commissioner, said RWE could be especially valuable in the post-marketing setting. "I think there's a huge opportunity in that early post-market phase," he said, noting that RWE could help determine a drug's best dosage. "Integration of care is what matters," he continued, and the U.S. health care system is almost impossible to integrate since it is so fragmented. He decried the fact that currently if data are aggregated, it is almost always for the benefit of financial organizations. He asked: "Where is it integrated for the benefit of the patient?
"What we need are standards for things like endpoints," Califf said. FDA has supported the use of RWE for regulatory decision-making and has issued guidance on the topic, stating that the agency hopes to learn more about a product from routine clinical care than it currently does. The Centers for Medicare & Medicare Services has been slower to work toward reliance on RWE for coverage decisions, although it has integrated RWE into some of its value-based payment models. "I think there's a real opportunity for federal agencies to collaborate," Califf stated.
Panelists at the meeting stressed the potential of RWE. "To a patient, treatment optimization is really important," said patient advocate Jane Perlmutter, PhD, MBA. "That's where RWE can help."
She stressed that the use of RWE can help establish efficacy in a larger patient population. In addition, it could help establish efficacy in off-label use. One pathway that could be useful is to establish RWE data collection registries, Perlmutter noted. She believes many patients would love to participate in such registries.
"Ultimately, the key is the quality of the data. Is it something we can trust?" said Donna Rivera, PharmD, MSc, Associate Director of Pharmacoepidemiology at FDA's Oncology Center of Excellence. "We're trying to conform real-world practice to a clinical trial." Does the endpoint represent the outcome? "It's about data integrity, ensuring the drug is safe and effective."
Rivera noted that RWE can have an impact on clinical trial design. She stressed that source standardization and methodological validation are important factors when using RWE to evaluate patients' response rates.
The Friends white paper states that there is growing recognition that real-world data, "when analyzed appropriately, can generate RWE in broader patient populations than clinical trials to inform treatment effectiveness, safety, and patient outcomes." The paper recognizes that strategies and methodologies are needed to align RWE to realize its full potential in oncology drug development. Also, it states that "great caution" should be taken when comparing real-world endpoints to clinical trial endpoints "given the inherent limitations of differing populations and measurements."
Peggy Eastman is a contributing writer.