Shawnalyn W Sunagawa, Lee C Winchester, Christopher S Wichman, Sean N Avedissian, David W Erikson, Molly Kernan, Mark A Marzinke, Timothy M Mykris, Renu Nandakumar, Thomas D Nolin, Anthony T Podany, Raymond E West, Beatrice A Chen, Catherine A Chappell, Kimberly K Scarsi
{"title":"Comparison of etonogestrel bioanalytical assay results in plasma and serum within and across laboratories.","authors":"Shawnalyn W Sunagawa, Lee C Winchester, Christopher S Wichman, Sean N Avedissian, David W Erikson, Molly Kernan, Mark A Marzinke, Timothy M Mykris, Renu Nandakumar, Thomas D Nolin, Anthony T Podany, Raymond E West, Beatrice A Chen, Catherine A Chappell, Kimberly K Scarsi","doi":"10.1016/j.contraception.2024.110720","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To compare performance characteristics of etonogestrel bioanalytical assays across laboratories.</p><p><strong>Study design: </strong>We conducted a blinded, six laboratory study: five academic laboratories and one contracted commercial laboratory (reference). Etonogestrel was quantitated at each laboratory in both prepared serum and/or plasma samples of six known etonogestrel concentrations, and in 60 clinical samples from participants using etonogestrel-containing contraceptive methods. Per regulatory guidance, laboratory accuracy (percent bias) and precision (coefficient of variation; CV) were defined as ±15% of the nominal prepared concentration. We compared inter- and intra-laboratory agreement using a Kendall's Tau-B and Passing-Bablok regression.</p><p><strong>Results: </strong>For prepared samples, six laboratories analyzed serum and three laboratories analyzed plasma. All etonogestrel results were within ±15% for accuracy across all concentrations at four labs, including the reference laboratory. All labs demonstrated high precision, with only one occurrence of CV >15%. We found a positive association between prepared plasma and serum etonogestrel results (Kendall's Tau-B 0.80-0.88). For clinical samples, five laboratories analyzed serum and three laboratories analyzed plasma. Compared to the reference laboratory, inter-laboratory serum etonogestrel concentrations were positively correlated (Kendall's Tau-B 0.76-0.95). Proportional bias was observed, meaning individual lab etonogestrel results were consistently higher (slope estimates 0.78-0.95) or lower (slope estimates 1.05-1.10) than the reference laboratory. In clinical samples, intra-laboratory results were well associated between plasma and serum (Kendall's Tau-B 0.92-0.96).</p><p><strong>Conclusion: </strong>There was good intra-laboratory agreement, irrespective of sample matrix; however, there was inter-laboratory variability in etonogestrel results. Differences between laboratory results should be considered when comparing etonogestrel pharmacokinetics across studies.</p>","PeriodicalId":93955,"journal":{"name":"Contraception","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contraception","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.contraception.2024.110720","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: To compare performance characteristics of etonogestrel bioanalytical assays across laboratories.
Study design: We conducted a blinded, six laboratory study: five academic laboratories and one contracted commercial laboratory (reference). Etonogestrel was quantitated at each laboratory in both prepared serum and/or plasma samples of six known etonogestrel concentrations, and in 60 clinical samples from participants using etonogestrel-containing contraceptive methods. Per regulatory guidance, laboratory accuracy (percent bias) and precision (coefficient of variation; CV) were defined as ±15% of the nominal prepared concentration. We compared inter- and intra-laboratory agreement using a Kendall's Tau-B and Passing-Bablok regression.
Results: For prepared samples, six laboratories analyzed serum and three laboratories analyzed plasma. All etonogestrel results were within ±15% for accuracy across all concentrations at four labs, including the reference laboratory. All labs demonstrated high precision, with only one occurrence of CV >15%. We found a positive association between prepared plasma and serum etonogestrel results (Kendall's Tau-B 0.80-0.88). For clinical samples, five laboratories analyzed serum and three laboratories analyzed plasma. Compared to the reference laboratory, inter-laboratory serum etonogestrel concentrations were positively correlated (Kendall's Tau-B 0.76-0.95). Proportional bias was observed, meaning individual lab etonogestrel results were consistently higher (slope estimates 0.78-0.95) or lower (slope estimates 1.05-1.10) than the reference laboratory. In clinical samples, intra-laboratory results were well associated between plasma and serum (Kendall's Tau-B 0.92-0.96).
Conclusion: There was good intra-laboratory agreement, irrespective of sample matrix; however, there was inter-laboratory variability in etonogestrel results. Differences between laboratory results should be considered when comparing etonogestrel pharmacokinetics across studies.