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Using RWE Pilot 2.0 to Confirm Internal Consistency in Clinical Trials

Using RWE Pilot 2.0 to Confirm Internal Consistency in Clinical Trials

This is the fourth installment in our Real-World Evidence (RWE) blog series where we highlight key findings and implications from the RWE pilot projects. You may view previous posts here, here, and here. In this post, we will review the Internal Consistency project, which investigated use of the RWE framework to select a clinical trial aligned population to compare outcomes.

Participants included in clinical trials may not reflect the general patient population in real-world settings. Rather, inclusion and exclusion criteria are used in clinical trials to help maintain the safety of patients enrolled in trials and integrity of the data. While necessary to understand the safety and efficacy of an investigational therapy, this information may not readily reflect real-world use and efficacy of a drug outside the confines of a randomized, controlled trial. With improved understanding of the strengths and limitations of datasets and validated outcomes measures, real-world data (RWD) presents an opportunity to generate evidence that can reflect a drug’s performance in real-world clinical practice and complement evidence generated in a clinical trial.

The Internal Consistency pilot sought to examine various real-world endpoints in a clinical trial-aligned population. KEYNOTE-189 acted as the “control” for the internal consistency project to assess if we could produce the same results using RWE. The KEYNOTE-189 clinical trial was chosen for alignment because it studied an immuno-oncology (IO) therapy (pembrolizumab) in combination with platinum chemotherapy compared to platinum chemotherapy alone in frontline treatment for patients with metastatic non-small cell lung cancer (NSCLC). We started with the original RWE 2.0 patient population and applied the pre-specified clinical trial inclusion and exclusion criteria from the KEYNOTE-189 clinical trial. When we applied the KEYNOTE-189 inclusion and exclusion criteria to the real-world patient population, we were able to align the characteristics of the Internal Consistency project population with the clinical trial population. These results imply the likelihood of a similar direction of treatment effect could potentially be observed in the real-world population.

The observation of improved survival on the investigational treatment over control in the clinical trial-aligned population in this study establishes important evidence supporting the use of RWE and real-world endpoints. The RWE pilot projects have tested the ability of RWD to address questions in drug development and created a framework to assess if real-world endpoints can be utilized in regulatory decisions. These projects would not have been possible without the collaborative effort of numerous stakeholders and research organizations. Our next post, and final installment in the RWE blog series, we will discuss the RWE whitepaper including lessons learned from the pilot projects and recommendations for the future use of RWE in oncology.


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