Real-world Data for Clinical Evidence Generation in Oncology

Abstract

Conventional cancer clinical trials can be slow and costly, often produce results with limited external validity, and are difficult for patients to participate in. Recent technological advances and a dynamic policy landscape in the United States have created a fertile ground for the use of real-world data (RWD) to improve current methods of clinical evidence generation. Sources of RWD include electronic health records, insurance claims, patient registries, and digital health solutions outside of conventional clinical trials. A definition focused on the original intent of data collected at the point of care can distinguish RWD from conventional clinical trial data. When the intent of data collection at the point of care is research, RWD can be generated using experimental designs similar to those employed in conventional clinical trials, but with several advantages that include gains in efficient execution of studies with an appropriate balance between internal and external validity. RWD can support active pharmacovigilance, insights into the natural history of disease, and the development of external control arms. Prospective collection of RWD can enable evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. PCTs may help address the growing demands for access to experimental therapies while increasing patient participation in cancer clinical trials. Conducting valid real-world studies requires data quality assurance through auditable data abstraction methods and new incentives to drive electronic capture of clinically relevant data at the point of care.

Enhancing global access to cancer medicines

“…Pragmatic trials with planned interventions, with or without randomization, can be conducted in real‐world settings (eg, PERSEPHONE) . Real‐world evidence could confirm the clinical benefit of cancer medicines that have undergone accelerated approval . Hybrid trials can be designed to incorporate traditional and pragmatic elements…”

An evaluation of the impact of missing deaths on overall survival analyses of advanced non–small cell lung cancer patients conducted in an electronic health records database

“…RWE sources, including EHR‐derived datasets, are valuable analytic platforms for conducting clinical research . Mortality serves as the primary outcome in many analyses across disease areas and particularly for oncology.…”

“…Real‐world evidence (RWE) generated from real‐world data (RWD), including data derived from electronic health records (EHRs), is increasingly important for pharmacoepidemiological research . These data provide opportunities for deriving clinical insights and serve to complement findings from clinical trials.…”

“…Although these analyses could involve multiple data sources, a strength of RWE is that datasets are often large enough that these questions can be addressed within a single, harmonized database, which leverages consistent data‐generating mechanisms across groups. Another emerging application for RWE is to serve as an external control arm for single‐arm trials, where every patient receives the experimental treatment . Although a control arm is not built into the study, researchers often wish to make comparisons between the experimental treatment and contemporaneous control treatments external to the trial.…”

From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study)

“…One of the aims of this network is to support observational real‐world and pragmatic clinical studies, which have the additional value of assessing safety and effectiveness of anticancer drugs in patients usually excluded from pivotal randomized clinical trials, often treated in smaller centers where resources and services are limited, and also allowing an active role in clinical research for community oncologists .…”