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One Day, Clinical Trials Will Represent the Real World


As the FDA’s Advancing Real-World Evidence (RWE) Program has developed in recent years, we’ve seen the agency become more open to innovative uses of RWE in clinical trial design. We’ve even seen a precedent-setting FDA acceptance of a hybrid external control, which combines synthetic control-arm patients with randomized patients in clinical trials.

Things are moving quickly, but it’s still very early in the process of using RWE to transform clinical trial design. Approvals to date based on RWE have focused largely on off-label uses for drugs whose initial approvals stemmed from conventional randomized controlled trial (RCT) designs. And many Life Sciences leaders are only now getting serious about using RWE in regulatory submissions. 

So what needs to happen for RWE to reach its fullest regulatory potential? We posed that question at a roundtable with industry leaders during the One Day Summit. Here are some takeaways.

Defining Rigor
RWE brings qualitative and quantitative data together like never before. Not only can you track toward traditional endpoints; because of advancements in the real-world data (RWD) ecosystem, you can also use RWE to show quality of life, an endpoint of great importance to patients. 

The original purpose of RWD was to glean insights from data collected during patient interactions with the healthcare system. Its role — to gather vast, sophisticated data from consumer devices of every kind — has expanded greatly, augmenting conventional data sources with patient-reported outcomes in the context of consented clinical trials. 

The key opportunity for bringing RWD into the mainstream regulatory process of trial design is in outlining and defining what needs to be controlled for in the RWE arm of a trial. Because of the breadth and depth of RWD, building these guardrails and rigor into the design of the control arm will give the industry and regulators confidence in the insights generated.

Taking Risks
Some leaders believe that every single phase 2 trial must include an RWE external control arm so that we, as an industry, can ensure the validity of the study and its results. This requires a level of risk-taking that many pharmaceutical companies may be uncomfortable with. However, it is the only way the industry can push the bounds of what’s possible. As Mathai Mammen, MD, PhD, and CEO of FogPharma said, “Regulators are working with sponsors ultimately to evolve. Without sponsors, there's no evolution of policy.”

Being Intentional With Representation
RWE can help achieve more representative clinical trials, but our roundtable participants debated about the goals of representation. Are we broadening control arms for greater diversity to ensure that they match the real world or to ensure we can get interventions to patients who wouldn’t normally have access? Representativeness, therefore, must be intentionally built into the trial design. 

Forming an Independent Committee
One participant suggested that forming an independent body to look at axes of value across all datasets and types could help establish what is sufficient and insufficient for extrapolation and where this data should be housed. Right now, across the industry, we lack standards for RWD. We pull guidance from different sources using different methodologies from different places, and each company has to process that data independently. The participant suggested that a collective, independent body that recommends data standards would add tremendous value.  

One Day: A Vision for Real-World Clinical Trials
The roundtable ended with a discussion of how the industry can hold up the successful evolution of biomarkers as an example of what is possible for RWE. Biomarkers used to be impossible to get on the market. After years of research and progress working alongside the FDA — we all know that finding strong biomarkers will certainly take extra work and resources — there is a path forward. So how do we clear a similar path for RWE? What do we need to prove, and how do we prove it? By developing a rigorous step-by-step process, we can prove that RWE can — and should — complement the randomized controlled trial (RCT).

The idea that we are seeing the central underpinning of Clinical Development transformed in this way is incredibly exciting. One day, RWE will be viewed as the standard complement to the RCT. And that day is not very far away.

For more insights about how Komodo is helping to transform clinical trials through RWE, read our blog, "The Impact of Inclusion/Exclusion Criteria on Clinical Trial Diversity".

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