Reimagining Traditional Oncology Clinical Trials with Real-World Data

As reported by The Financial Times this weekend, the power of data to accelerate drug discovery and research represents fresh hope for patients. I believe we are only at the beginning of utilizing the power of real-world data (RWD) to generate real-world evidence (RWE) that could be used towards clinical study design and execution, trial interpretation, and regulatory submissions. The exponential growth of RWD sources is creating a vibrant policy and regulatory landscape, encouraged by the enactment of the 21st Century Cures Act, which requires the FDA to develop guidance for how RWD may inform regulatory decisions (for example: label expansions and new indications for existing therapies). With its accelerated pace and intensity, the Oncology community should be at the forefront of developing the tools and ‘know-how’ to apply RWE to drug development.

RWD is a term used to refer to healthcare-related data collected outside of the traditional clinical trial setting. This can include data from patient visits with healthcare providers captured in electronic health records (EHRs); patient registries; insurance claims; patient-generated data from wearables; information from social media posts; or home devices such as blood pressure self-monitoring kits. EHRs, registries, and claims databases often contain granular data that are being collected in real-world settings at the point of care. These data, once analyzed and validated, may be used to generate RWE — clinical insights or evidence extracted from real-world sources about the use and potential benefits or risks of a medical product that may be used to inform treatment decisions. A primary feature distinguishing RWE from other kinds of clinical evidence is the context in which the evidence is assembled — for example in-home or community settings as opposed to research-intensive environments. 

RWE can be applied to and support drug discovery and development from target identification to analyzing the use, adherence, efficacy and safety of medicines in the real world. The use of RWE has the potential to allow us to answer questions efficiently regarding a medicine’s efficacy and safety in a non-academic setting, saving time and money while yielding answers relevant to broader populations of patients than would be possible in a restrictive research environment.

At Pfizer Oncology, our vision is to integrate RWE across the development of each new molecular entity and our approved cancer medicines. The overall aim is to accelerate targeted medicine development, improve equitable access, and evolve cancer care delivery models. Ultimately, ensuring we get the right medicine, to the right patient at the right time. 

A common misconception is that prospective RWE studies are mutually exclusive and could eventually replace randomized controlled trials. Randomized trials are the “gold standard” framework for defining the efficacy and safety of therapies; the vigor of their design enables comparisons of relative efficacy by minimizing confounding factors, and most importantly, randomized studies control for the ‘unknowns,’ minimizing bias by matching underlying risk between treatment groups.

Studies utilizing RWD should be used to complement or enhance randomized clinical trials and our aim is not to substitute randomized studies. Also, RWE can be generated through randomized trials (for example: large ‘unfussy’ real-world setting studies and pragmatic clinical trials). 

However, the internal vigor achieved by randomized clinical trials can be at the expense of generalizing to the ‘real-world’ setting, especially since clinical trials often have restrictive inclusion criteria (for example: age, concomitant illnesses and medications, performance status). In addition, patients from lower socioeconomic backgrounds and certain ethnicities are under-represented in clinical trials, and adherence to therapies and management of adverse events are more robustly supported in a controlled setting than what is achievable in routine clinical practice. But large randomized clinical trials reporting results of marginal clinical significance for the highly selected patients recruited to them can also be misleading, compared to substantial clinical benefit noted in a well-designed RWE observational study.

Overall, RWE yields significant insights to complement clinical trials by offering a way to observe the effectiveness and risks of therapies in routine clinical practice, providing additional insights into the broader patient experience. When employed appropriately, RWE can close the evidence gap between clinical research and real-world clinical practice.

In future posts, I will go deeper into how we are utilizing RWE across the full medicine development lifecycle at Pfizer Oncology, with the goal of delivering more medicines to smaller and underserved patient populations, faster.