Mimi Traylor-Knowles co-wrote this blog post with Maria Whitman.
At the 2017 Annual Society of Clinical Oncology Annual Meeting (ASCO), Dr. Sean Khozin, senior medical officer at the FDA, opened his Saturday session with some trivia: When was the first controlled clinical trial? The answer, which surprised many of my fellow attendees, was 1747, when James Lind held a trial to determine if citrus juice would help control the symptoms of scurvy. Dr. Khozin then showed a timeline to demonstrate the history of controlled clinical trials. He concluded his session with a single but poignant visual: a flat line stretching more than 250 years from then until now. As the world has made historic progress in innovation—from steam locomotives to a man on the moon to the internet and all that we have today—controlled clinical trials have remained largely the same.
The importance of randomized clinical trials is unchallenged: They remain the gold standard and the requirement for therapy approvals. But the reality of each patient’s unique situation forces us to consider how to get to a closer and better decision based on a unique individual. Ultimately, real-world evidence presents an opportunity to enhance our understanding and use of interventions to deliver better patient care: right therapy, right patient, right time.
Dr. Yousuf Zafar, an associate professor of medicine at Duke University, spoke with me at ASCO to discuss the differences between real-world evidence and randomized clinical trials, and the balance that he sees between them in the future. He noted that while randomized clinical trials are important and help remove biases that allow us to gauge effectiveness, they also help us understand the options for treating a group of patients with stage IV colorectal cancer who fit the trial protocol, for example. But is there enough information to determine the best treatment for a 50-year-old patient with colorectal cancer who also has severe diabetes and plays the piano?
Dr. Zafar describes real-world evidence as “collecting data from patients and from health systems in a way that’s representative of the environment in which those patients were treated.” While this data brings us closer to comparison to a specific individual patient—in contrast to randomized clinical trials that seek to remove bias—real-world evidence can be laced with real-world, hidden biases.
Both have their strengths and limitations, and one isn’t expected to overrule the other. In fact, the growing consensus is that they need to be used together. At ASCO, the FDA shared its perspective about the utility of both real-world evidence and randomized clinical trials. The FDA is actively working on using real-world evidence from electronic health record systems to help guide regulatory decisions. At the event, ASCO, the FDA and the National Cancer Institute reaffirmed their partnership with CancerLinQ, an initiative to collect, share and tap into real-world evidence from ASCO members’ cancer patients via their EMR systems. The goal of the partnership is to assess recently approved therapies to better inform how they should continue to be used, and also to inform future drug reviews and labeling refinements.
Furthermore, ASCO showed that payers are expressing interest in real-world evidence. At the same session as the FDA presentation, Dr. Alan Rosenberg, vice president of clinical pharmacy and medical policy at Anthem, shared one payer’s perspective on the impact of real-world evidence in coverage decisions. Dr. Rosenberg said that payers do indeed consider real-world evidence when making coverage decisions, and that while FDA approval is required for coverage, it may not be sufficient. In a different session, Lee Newcomer, senior vice president of oncology and genetics at UnitedHealthcare, described a portal that UnitedHealthcare will soon launch in order make de-identified data available to providers in the hopes that it will help with treatment decisions.
These movements toward harnessing the value of real-world evidence show us that while randomized clinical trials will continue to set the standard, real-world evidence will be looked to more and more to make personalized decisions for patients. Dr. Zafar expects that several factors will help reduce the limitations of real-world evidence in the future:
- Sheer volume: The more real-world evidence that’s generated, the less likely that hidden biases will be found.
- Standardization: Once we identify which data points are the most important to look at, we can collect those metrics consistently and rigorously.
Will real-world evidence get to a point where, in certain situations, it can replace versus complement certain decisions? That’s still unclear, but it’s an important time for stakeholders across the cancer care landscape to start thinking about their roles in the advancement of real-world evidence so that we can continue to improve our ability to make the best possible treatment decisions for patients.