title: The Immunology Quality Assessment Proficiency Testing Program for CD3⁺4⁺ and CD3⁺8⁺ lymphocyte subsets: a ten year review via longitudinal mixed effects modeling.
abstract: Since 1999, the National Institute of Allergy and Infectious Diseases Division of AIDS (NIAID DAIDS) has funded the Immunology Quality Assessment (IQA) Program with the goal of assessing proficiency in basic lymphocyte subset immunophenotyping for each North American laboratory supporting the NIAID DAIDS HIV clinical trial networks. Further, the purpose of this program is to facilitate an increase in the consistency of interlaboratory T-cell subset measurement (CD3(+)4(+)/CD3(+)8(+) percentages and absolute counts) and likewise, a decrease in intralaboratory variability. IQA T-cell subset measurement proficiency testing was performed over a ten-year period (January 2003-July 2012), and the results were analyzed via longitudinal analysis using mixed effects models. The goal of this analysis was to describe how a typical laboratory (a statistical modeling construct) participating in the IQA Program performed over time. Specifically, these models were utilized to examine trends in interlaboratory agreement, as well as successful passing of proficiency testing. Intralaboratory variability (i.e., precision) was determined by the repeated measures variance, while fixed and random effects were taken into account for changes in interlaboratory agreement (i.e., accuracy) over time. A flow cytometer (single-platform technology, SPT) or a flow cytometer/hematology analyzer (dual-platform technology, DPT) was also examined as a factor for accuracy and precision. The principal finding of this analysis was a significant (p<0.001) increase in accuracy of T-cell subset measurements over time, regardless of technology type (SPT or DPT). Greater precision was found in SPT measurements of all T-cell subset measurements (p<0.001), as well as greater accuracy of SPT on CD3(+)4(+)% and CD3(+)8(+)% assessments (p<0.05 and p<0.001, respectively). However, the interlaboratory random effects variance in DPT results indicates that for some cases DPT can have increased accuracy compared to SPT. Overall, these findings demonstrate that proficiency in and among IQA laboratories have, in general, improved over time and that platform type differences in performance do exist.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bainbridge
authors.affiliation: Statistical Analysis and Data Center, Boston, MA, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Wilkening
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Rountree
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA. Electronic address: raul.louzao@duke.edu.
authors.forename: R
authors.initials: R
authors.lastname: Louzao
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: N
authors.initials: N
authors.lastname: Perza
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Denny
mesh_terms: D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000097:blood*; D018791:CD4 Lymphocyte Count / Q000592:standards* / Q000706:statistics & numerical data; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002986:Clinical Trials as Topic / Q000592:standards* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D005434:Flow Cytometry / Q000592:standards; D019983:Guideline Adherence / Q000592:standards; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D006801:Humans; D016130:Immunophenotyping / Q000592:standards* / Q000706:statistics & numerical data; D007753:Laboratories / Q000592:standards* / Q000706:statistics & numerical data; D059021:Laboratory Proficiency Testing / Q000592:standards* / Q000706:statistics & numerical data; D015233:Models, Statistical; D015166:Monitoring, Immunologic / Q000592:standards* / Q000706:statistics & numerical data; D015588:Observer Variation; D017410:Practice Guidelines as Topic / Q000592:standards; D011237:Predictive Value of Tests; D016730:Program Development; D015397:Program Evaluation; D011786:Quality Control; D058996:Quality Improvement; D019984:Quality Indicators, Health Care / Q000592:standards; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000592:standards; D013997:Time Factors; D057188:Workflow
chemical_list: D015415:Biomarkers; D017252:CD3 Complex
keywords: Flow cytometry; IQA; Longitudinal analysis; Lymphocyte subset phenotyping; Mixed effects models; Proficiency testing