[906716]
Idenix pharmaceuticals ( cambridge, ma) ("idenix") contracted with centron diagnostics, ltd. ( austin, tx) ("cenetron") to provide molecular virology central laboratory services for a phase i clinical trial, protocol which begin in early 2008. The sole clinical site for this trial is located in buenos aires, argentina. The final study protocol specified the use the roche cobas ampliprep/cobas taqman assay ("taqman assay") to measure plasma rna concentrations. Early into the clinical trial, a higher than expected number of pts were excluded from the study, largely because of screening viral loads that fell below the minimum inclusion criteria. Additionally, lab testing of the samples by a local lab, using the roche cobas amplicor monitor assay (" amplicor assay") assay produced results which were significantly higher than those from cenetron. A review of the sample collection, handling and shipping procedures revealed no obvious problems that would produce discordant results. Cenetron sent samples with the most questionable results to another lab in the us for confirmatory testing with the taqman assay, and the results were virtually identical to those produced at cenetron. Cenetron then retested a number of samples (52) with the amplicor assay and was able to reproduce the discordant results seen at cibic. At this point, cenetron contacted the test mfr about the discordance between the two assay platforms. In 2008, a roche technical services rep visited cenetron and called in the problem to the mfr's technical service dept, and initiated case. After discussions with the study sponsor, cenetron re-tested all specimens previously received during the trial with the amplicor assay, and also began testing all samples with both assays going forward. By the next month, the first 3 cohorts of pts had completed the trial (pts screened, some enrolled, and samples tested with both assays ). On the next day, a complete slide set for an upcoming meeting, the xvii international drug resistance workshop "resisting meeting" were sent to roche. Preliminary results from this study were presented in a talk by a dr(school of med. ) at the resistance meeting in other country ( june 10-14, 2008) which included slides which addressed the discordance assay results. Analysis of the first total pts shows that 7/30 (22%) pts had partially discordant viral load response patterns, and 6/30 (20%) had markedly discordant viral load patterns. The taqman assay results were lower than the amplicor values in all pts that were either partially discordant or fully discordant. Longitudinal data shows a compelling consistency in the discordance between the 2 assays in serial samples from the same pt(s), which strongly suggests that discordance is not random, but related to the genetic makeup of the viral quasispecies that infect specific patients. Similar finding were reported. (clinical microbiology, 2007), where 25 % of total pts were " underquantitated" by at least 0. 5 logs by the taqman assay. On 17- june-08, we discovered a product advisory notice on the web site, issued by roche on 8-jan-2008, in the other country, in which the " possible influence of mutations on the detection and/or quantitation of genotypes/subtypes of viruses with pcr tests" was reported with the hiv-1 taqman assay as a potential safety issue, at an "action required" level. For the same safety reasons cited in this product advisory report, we are filing this voluntary report.
Patient Sequence No: 1, Text Type: D, B5