Effectiveness versus Efficacy of Calabadion and Sugammadex for Nondepolarizing Neuromuscular Blocking Agent Reversal

Haerter et al.¹  recently published a study on the comparison of calabadion 2 to reverse nondepolarizing neuromuscular blocking agents by binding and inactivation, which they described as comparative effectiveness. The study included in vitro, ex vivo, and in vivo experiments, including assessments of dose–response relationships. Although the article makes some important contributions, our concern focuses on the use of the term and the associated title that includes “comparative effectiveness.” Instead, these studies should be described as efficacy research, not effectiveness research. Although this distinction may seem to represent a minor issue, we feel that incorrectly defining the phase of research can lead to misconceptions about the study’s goals and objectives, and subsequent interpretation, and lead to misreporting on the current state of research (e.g., in a systematic review with searches based on titles and key terms).

Although Haerter et al. do not use the full term of “comparative effectiveness research” (CER), the idea of effectiveness, rather than efficacy, is well described by extensive literature on CER. The Institute of Medicine²  and Federal Coordinating Council for Comparative Effectiveness Research³  describe CER as “…the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care.” The Institute of Medicine report goes on to state that “The key elements of this definition are … the study of patients in typical day-to-day clinical care.” In contrast, efficacy studies evaluate treatments under ideal conditions, with an emphasis on assessing the potential of the intervention to work under ideal or very specific conditions. The study by Haerter et al. demonstrates which drugs work best in a laboratory setting and in controlled circumstances. While these findings are absolutely informative and significant, they do not demonstrate effectiveness in that they do not reveal which drugs work well in a less controlled, “real-world” clinical setting.

The distinction between efficacy and effectiveness is also emphasized by the phases of translational research,⁴  where efficacy studies qualify as T1 or T2 research, but effectiveness studies fall under T3 research. Although the study by Haerter et al. compares treatments, the in vitro, ex vivo, and in vivo nature of experiments would still lead to its categorization as T1 research.

Supported in part by National Institutes of Health (Bethesda, Maryland) grant T32GM075770 (to Dr. Lim).

The authors declare no competing interests.