Randomized clinical trials (RCTs) are considered the main source of data driving evidence-based practice and the primary method for establishing the efficacy of an intervention. However, for a variety of reasons, the universe of research questions that can be definitively addressed by traditional RCTs is limited.¹ At the heart of comparative effectiveness research (CER) is a desire to generate real-world evidence demonstrating the effectiveness (rather than the efficacy) of an intervention using real-world data (obtained outside the often-ideal conditions of a traditional RCT). As value-based reimbursement models are better integrated into the US health care system and patient-centered care is increasingly emphasized, there will be a greater need for high-quality CER studies to inform the most clinically effective and cost-effective treatments and to help identify the right type of treatment for patients being treated in specific clinical contexts.