However, in Phase 2 trials subjects with detectable/BLOQ HCV RNA at the current RGT decision points (week 8 for boceprevir, week 4 for telaprevir) generally achieved a higher SVR rate and lower relapse rate with an extended duration of treatment. Based on the totality of data presented here, clinicians prescribing boceprevir or telaprevir are cautioned not to consider detectable/BLOQ HCV RNA equivalent to undetectable HCV RNA for the purpose of shortening treatment duration. Metformin solubility dmso Product inserts for both boceprevir and telaprevir state that for the purpose of assessing RGT eligibility, “a confirmed ‘detectable but below limit of quantification’

HCV-RNA result should not be considered equivalent to an ‘undetectable’ HCV-RNA result.”12, 13 Using a nonvalidated,

making with boceprevir- or telaprevir-based regimens could result in suboptimal SVR rates and elevated relapse rates. In addition, our analyses of the treatment-free follow-up period for SVR-achieving buy CH5424802 subjects demonstrated there can be variability in the rate at which detectable/BLOQ results are reported by different contract laboratories using the same HCV RNA assay. Vendor B reported an unexpectedly high rate of detectable HCV RNA results during follow-up among SVR-achieving subjects for telaprevir Study 108, which we hypothesize represents a higher rate of false-positive HCV RNA detection throughout the conduct of the trial. In fact, reanalysis of a subset of Study 108 samples by Vendor A yielded a reduced frequency of detectable/BLOQ results, particularly for follow-up samples from 上海皓元医药股份有限公司 subjects who achieved SVR. Furthermore, the rate at which such follow-up results

were reported by Vendor A for the P05216 and C216 trials is comparable to the recognized false-positive detection rate of the assay: ≈1.3%, according to the FDA-approved assay package insert.17 A higher rate of reported detectable/BLOQ results during treatment and follow-up by Vendor B could explain the decreased difference in SVR rates between subjects with on-treatment detectable/BLOQ versus undetectable HCV RNA levels relative to that observed for the P05216 and C216 trials. However, despite the unexpectedly high rate of detectable/BLOQ results during and following treatment in Study 108, SVR rates remained consistently higher for subjects with undetectable HCV RNA at any given timepoint during treatment compared with those with detectable/BLOQ at the same timepoint. Currently, it is not clear why the detectable/BLOQ reporting frequency varied by contract laboratory, whether such variability still exists, and whether it extends across other laboratories that typically conduct HCV RNA assessments. We cannot confirm the same technical procedures were used by the different laboratories for the Roche COBAS TaqMan HCV 2.0 assay used in the clinical trials.