Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies.

Background & Aims: Trials of therapies for chronic hepatitis C have used detection of hepatitis C virus (HCV) at week 24 of follow-up (sustained virologic response [SVR] 24) as a primary end point. However, there is increasing evidence that most patients who have an SVR at earlier time points (such as SVR12) maintain it until week 24. Use of earlier time points for key regulatory decisions (SVR12) and dose selection (SVR4) could facilitate HCV drug development.

Response-guided telaprevir therapy in prior relapsers? The role of bridging data from treatment-naïve and experienced subjects.

The purpose of this report is to illustrate the US Food and Drug Administration's rationale for approving response-guided therapy (RGT) for telaprevir (TVR) in combination with pegylated interferon-α and ribavirin (P/R) for the treatment of adults with genotype 1 chronic hepatitis C who were prior relapsers. RGT was prospectively evaluated in two registration trials of treatment-naïve subjects. In these studies, RGT allowed subjects who achieved undetectable hepatitis C virus RNA from weeks 4 and 12, known as extended rapid virologic response (eRVR), to stop all treatments at 24 weeks.

Meeting the demand for more sophisticated study designs. A proposal for a new type of clinical trial: the hybrid design.

Background Treatment effect is traditionally assessed through either superiority or non-inferiority clinical trials. Investigators may find that because of safety concerns and/or wide variability across strata of the superiority margin of active controls over placebo, neither a superiority nor a non-inferiority trial design is ethical or practical in some disease populations. Prior knowledge may allow and drive study designers to consider more sophisticated designs for a clinical trial.