One of the most widely recognised limitations of traditional randomised clinical trials (RCTs) is that the observation period and treatment courses reflect only a fraction of the natural history/ progression of the disease being investigated on an often miniscule and idiosyncratic subset of patients. Henry J. Riordan et al. of Worldwide explore how to close the evidence gap between the data evaluated by regulators for approval, which is by definition derived from idiosyncratic RCTs, and the real-world data used by healthcare providers, payers and consumers to inform clinical practice.