Effectiveness research in the evolving HCV landscape.

As antiviral therapy for chronic hepatitis C virus (HCV) infection continues to evolve, understanding the effectiveness of antiviral regimens is critical for making informed treatment decisions for HCV management. While the terms ‘‘efficacy’’ and ‘‘effectiveness’’ are often used interchangeably, they hold different meanings: Efficacy is a measure of the capacity of a treatment to produce the desired effect in a controlled environment, such as in a randomized controlled trial whereas effectiveness describes the actual effect of the treatment in practice [1]. In HCV antiviral clinical trials, like other clinical trials, patients are screened using stringent predetermined criteria, closely monitored, and any treatment deviations must follow detailed protocols. As such, information provided in traditional randomized clinical trials is often limited when applied to clinical practice where variation of patient characteristics, setting, care coordination, and management cannot be controlled. These elements are likely to influence the magnitude of the effect in practice depending on who is treated, how they are treated, which conditions are being treated and other nuances. Effectiveness studies, which examine effects (outcomes) in actual practice, provide practical information to address the ‘‘where,’’ ‘‘how,’’ and ‘‘for whom’’ a treatment might be recommended depending on the questions addressed, patient population, groups compared, setting, and measured outcomes. Though the randomized controlled trial is often held up as the ‘‘gold standard’’ for medical decision making, truly informed decision making requires information obtained from clinical practice. In this issue of Digestive Diseases and Sciences, Price et al. [2] examine real-world treatment outcomes in a comparative effectiveness study of boceprevir and telaprevir in an insured US HCV-infected population. In this large integrated care setting, those undergoing treatment initiation were frequently cirrhotic and treatment-experienced groups, groups usually underrepresented in clinical trials of boceprevir and telaprevir. Almost a third of patients in this study discontinued treatment prematurely, most often patient-initiated and commonly related to adverse effects. Sustained virological response (SVR) rates were notably lower than reported in clinical trials: 48–54 % for boceprevir-based regimens and 31–67 % for telaprevir-based regimens depending on prior HCV treatment experience and stage of liver disease. The findings underscore the differences between ‘‘real-world’’ HCV care experiences and clinical trials. The observed SVR rates serve as further documentation of the decrement in effectiveness when moving from the clinical trial to clinical practice. With current advances in HCV treatment and approval of newer, better tolerated, and less complex regimens, the use of boceprevir and telaprevir regimens is expected to be greatly reduced. Yet, results from this study and other comparative effectiveness studies are still useful. The differences observed in this study with regards to patient characteristics, early treatment discontinuations, adverse effects, and lower SVR rates reflect the differences between clinical trials and clinical practice. Perhaps more importantly, it demonstrates that providers, patients, and payers need to appropriately temper expectations about Views expressed here are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs.