OBJECTIVES: Increased transparency, protocol registration and more rigorous quality standards have improved confidence in the validity of observational research. However, limiting analyses to a predefined protocol without allowing for flexibility reduces the potential to uncover new insights during study conduct. Rapid Evaluation Processes (REP) supplement standard research with ad-hoc hypothesis generation, evaluation, and delivery of actionable results within short timeframes. METHODS: REP adapts research processes into a streamlined yet flexible format whereby a study-specific analytic platform is developed in advance and then customized based on “breaking news”. A focused team produces results for immediate discussion and action, generating high impact results far more quickly than typical research timelines. Case examples include a global avian influenza outbreak, which produced a critical need to evaluate effectiveness of off-label treatment for rapidly occurring cases; sports injury surveillance, where effectiveness of rule changes require in-season evaluation based on trends in week-to-week injury occurrence; and market uptake of new therapies which impact enrollment and analytic methods. RESULTS: REP adds tangible value in settings where current events such as safety reports, new and highly utilized treatments, rapid development of cases (e.g., diseases or injuries), reimbursement or policy changes, evolving epidemics, or media speculation drive changes in treatment or outcome recognition.  Vaccine and antibiotic surveillance programs and evaluation of risk minimization programs within drug utilization studies, often mandated by regulators, are also key research objectives that can be addressed by REP. CONCLUSIONS: REP enables timely exploratory analyses that generate hypotheses, provides understanding of rapidly changing disease settings or medication use, delivers inputs into needed changes in active study enrollment or operations, and answers time-sensitive questions about patient health.