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":"血浆和血清中依托诺雌醇生物分析测定结果在实验室内和实验室间的比较。","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":"{\"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}","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}
Comparison of etonogestrel bioanalytical assay results in plasma and serum within and across laboratories.
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.