RWD: Responding to regulatory and drug development challenges

Rebecca Miksad, MD, MPH, a senior medical director of Flatiron Health, medical oncologist and health outcomes researcher, discusses how real-world data address regulatory and drug development challenges.

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Often, a gap exists between the outcomes of therapeutic interventions in clinical trials and those experienced by patients living in the wider world. Clinical realities such as genomic testing, patient organ dysfunction, and treatment patterns of real-world practice may diverge from those in trial settings and change over time in response to new data. The ever-evolving scientific and regulatory landscapes call for complementary sources of information to be considered alongside clinical trials. Meanwhile, the speed at which promising new therapeutics are proliferating makes head-to-head randomized controlled trials for all drugs in all settings infeasible. Collecting and crunching real-world data (RWD) helps address these issues by dipping into wells of information derived from a broad spectrum of patients. So, how might the rapidly evolving field of real-world evidence (RWE) affect the current paradigm for drug development and approval?

Rebecca Miksad, MD, MPH, a senior medical director at Flatiron Health, is a medical oncologist and health outcomes researcher who focuses on applications of real-world evidence in oncology. Her responses to our questions below are excerpted from the Executive Education at HMS webinar, “Applying Real-World Evidence to Regulatory and Drug Development Challenges.”

Interview has been edited and condensed for clarity.

What is real-world data?

In 2018, the FDA issued a framework for their Real-World Evidence Program. According to FDA definitions, real-world data are information derived from health care that is delivered outside of the traditional clinical trial setting. This includes electronic health records (EHR), claims data, administrative data, registries, and patient-generated health data such as from wearables. And we really believe that this data complements clinical trials, particularly because it may be more generalizable knowledge than may be drawn from clinical trials, which may underrepresent certain populations, such as those with organ dysfunction.

The continuum of evidence starts in clinical practice and extends through retrospective real-world data to prospective real-world data to clinical trial data sets. Retrospective real-world data captures and collates data already available in the EHR that was collected due to standard of care. In a prospective real-world data setting, you could have a pragmatic trial that uses the EHR after getting patient consent.

One question I often hear is: why now? Multiple factors have enabled the logistical, data storage and electronic aspects of the EHR to really become a powerful engine to develop real-world data.

Why is real-world evidence so valuable?

This really goes back to patients. Patients, families and clinicians need good data to make informed health care decisions. Clinical trials only answer a subset of questions. And the patients we see in clinic represent very different types of patients with very different types of medical problems than patients who are able to enroll in a clinical trial.

Let’s take cancer as an example. Someone once asked me why researchers can’t just enroll more patients in trials? We would love to, but less than 10% of cancer patients actually ever get enrolled in a clinical trial. And with the advent of new therapies like immunotherapy, the number of open trials continually increases. Up to 46% of oncology trials take more than two years to meet enrollment goals. This essentially means we don’t have enough patients to answer the questions we want to ask. Concurrently, oncology post-market commitments are accumulating faster than they can be fulfilled: the accumulation of regulatory debt is dramatic. Post-marketing commitments allow the FDA, physicians and patients to really understand how a drug works in patients, while still getting access to the drug early.

What can we learn from real-world evidence use cases?

Oncology is a great use case because there’s a high unmet medical need. Real-world evidence may be particularly valuable in this context. And we know that, due to the 21st Century Cures Act, the FDA, in drug development and approvals, is looking for these additional sources of information. That’s why it’s important for folks in business to understand what real-world evidence is and how it may be useful in a regulatory setting.

Also, rapidly changing standards of care make real-world evidence important. Take the adoption of PD-1/PD-L1 therapies in first-line treatment. If we looked at studies from even five or 10 years ago, the standard of care was completely different. This makes it very hard to put in context any single-arm trials that you currently might be running. Yet a retrospective, multicenter analysis with de-identified EHR data collected during routine clinical care allowed us to fill in knowledge gaps about the real-world performance of PD-1 and PD-L1 inhibitors, including data on the relationship of testing rates on overall survival and real-world progression free survival.

– Francesca Coltrera

Click here to see the full webinar, “Applying Real-World Evidence to Regulatory and Drug Development Challenges,” which delves more deeply into this topic.

Continue the conversation on Twitter by connecting with us @ExecEd or with Dr. Miksad @RMiksad.