An Innovation Spotlight argues that synthetic control arms—generated from external datasets instead of traditional placebo groups—are changing how investigators plan clinical trials. The piece highlights how externally derived control data can reduce recruitment burden and potentially mitigate ethical concerns tied to withholding therapy. The discussion also notes the growing methodological split between statistical or machine-learning methods that produce fully synthetic control data and approaches that generate synthetic/external control arms using real-world and historical hospital or trial information. A use case emphasized in the report is idiopathic pulmonary fibrosis, where flexible control-arm generation and imaging biomarkers may help address power and feasibility constraints common to complex indications.