Friends of Cancer Research (Friends) convened a working group to characterize methodological processes and to discuss the implementation and opportunities for formal regulatory use of external controls. This whitepaper describes several approaches to constructing an external control and also considers the use of hybrid designs that supplement or augment the control group in the randomized control trials (RCT) with data from an external population. This whitepaper further discusses statistical methodology to help address potential biases and improve the usefulness of the data as well as other adjustment methods that rely on patient summary data. In addition, we describe several scenarios where the use of external controls may be advantageous and practices that can help guide the implementation within a clinical study. A use case was prepared that characterizes the construction of an external control using clinical trial data in multiple myeloma to compare the treatment effect with a randomized control versus an external control and assesses the potential impact of unmeasured confounders.