Clinical Pharmacology Quality Assurance Program

Abstract

Among National Institutes of Health (NIH) HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals (ARV). Drug assay data are, in turn, entered into study-specific datasets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semi-annual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance (CPQA) program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1)assess the precision and accuracy of concentrations reported by individual CPLs; (2)determine factors associated with round-specific and long-term assay accuracy, precision and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21)drug concentration results reported for clinical trial samples by multiple CPLs).Using the CLIA acceptance of meeting criteria for ≥2/3 consecutive rounds, all ten laboratories that participated in three or more rounds per analyte maintained CLIA proficiency. Significant associations were present between magnitude of error and CPL (Kruskal Wallis [KW]p<0.001), and ARV (KW p<0.001).

Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy

“…The extracted samples are separated by reverse phase chromatography and detected by tandem mass spectrometry using electrospray positive ionization with multiple reaction monitoring (MRM) mode. The assay range is 0.05 – 20.0 ng/mg for LPV and the UCSF HAL assay has been peer reviewed and approved by the Division of AIDS (DAIDS) Clinical Pharmacology and Quality Assurance (CPQA) program [14] .…”

Adding Value to Antiretroviral Proficiency Testing

“…The CPLs reported results using the Laboratory Data Management System (version 5.6 – 6.1, Frontier Science Technology and Research Foundation); the results were compiled by the CPQA data management team. Additional information on the CPQA PT program operations has been reported in recent publications [2,17]. …”

“…To evaluate associations between intra- or inter-assay variability and CPL, ARV or concentration level, the Kruskal-Wallis (KW) test was performed independently for each variable at the 5% level of significance. For each variable exhibiting statistically significant differences among RPD or RSD via KW: [1] outcome measures (RPD or RSD) were ranked, [2] a one-way analysis of variance model (ANOVA) was fit to the ranks, and [3] all pairwise comparisons were conducted using the Tukey test with 5% family-wise error rate. For lipemia and hemolysis effects, each CPL and ARV was considered independently, due to potential assay differences affecting specificity (e.g.…”

“…The Clinical Pharmacology Quality Assurance Program (CPQA) provides PT for antiretrovirals (ARVs) in clinical trial protocols conducted by the National Institute of Allergy and Infectious Diseases (NIAID). The CPQA has recently reported data from the initial four PT events [2]. The ARVs tested included 9 HIV-1 protease inhibitors (PI), 3 HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI), 7 nucleoside reverse transcriptase inhibitors (NRTI), 1 CCR5 antagonist and 1 integrase strand transfer inhibitor (INSTI).…”

Introduction to a Special Issue of the Journal of Immunological Methods: Building Global Resource Programs to Support HIV/AIDS Clinical Trial Studies

“…While not featured here, it should be noted that other HIV EQA programs, including the Virology Quality Assurance (VQA), IQA Cryopreservation Program and Clinical Quality Assurance Program (CQAP), have made contributions to EQA globally (Brambilla et al, 2001; Brambilla et al, 2004; Jennings et al, 2005; Weinberg et al, 2007; Jennings et al, 2012; DiFrancesco et al, 2013). …”