Evidentiary challenges in comparative effectiveness research

“What healthcare treatment works best, for whom, and under what circumstances?” is the central question of comparative effectiveness research (CER). This paper first defines CER, and then briefly discusses its policy origins, the Patient-Centered Outcomes Research Institute (PCORI), and the relationship of CER to other evidence-based medicine approaches. PCORI methodology standards for the conduct of CER are described. Specific evidentiary challenges including the need to include observational data, and assess heterogeneity of treatment effects, are identified. The last section of this paper focuses on how evidence from a systematic review, a common study design in CER, is interpreted for decision-making. Methods for assessing the strength of evidence across a group of studies are described. These assessments are used for decisions at the individual patient level as well as the public health perspective, for example to determine clinical practice guidelines. The challenges inherent in these methods are presented, along with the results from a reliability study. The implications for CER decisions and decision-makers are important to consider.