Volume 22, Issue 3 pp. 461-474
MAIN PAPER

Statistical considerations for assessing precision of heterogeneous duplicate measurements: An application to pharmaceutical bioanalysis

Jorge Quiroz

Corresponding Author

Jorge Quiroz

Merck & Co., Inc., MRL, Research CMC Statistics, Kenilworth, New Jersey, USA

Correspondence

Jorge Quiroz, Merck & Co., Inc., MRL, Research CMC Statistics, Kenilworth, NJ, USA.

Email: [email protected]

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Satrajit Roychoudhury

Satrajit Roychoudhury

Global Biometrics & Data Management, Pfizer Inc., Peapack, New Jersey, USA

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First published: 21 December 2022

Abstract

Duplicate analysis is a strategy commonly used to assess precision of bioanalytical methods. In some cases, duplicate analysis may rely on pooling data generated across organizations. Despite being generated under comparable conditions, organizations may produce duplicate measurements with different precision. Thus, these pooled data consist of a heterogeneous collection of duplicate measurements. Precision estimates are often expressed as relative difference indexes (RDI), such as relative percentage difference (RPD). Empirical evidence indicates that the frequency distribution of RDI values from heterogeneous data exhibits sharper peaks and heavier tails than normal distributions. Therefore, traditional normal-based models may yield faulty or unreliable estimates of precision from heterogeneous duplicate data. In this paper, we survey application of the mixture models that satisfactorily represent the distribution of RDI values from heterogeneous duplicate data. A simulation study was conducted to compare the performance of the different models in providing reliable estimates and inferences of percentile calculated from RDI values. These models are readily accessible to practitioners for study implementation through the use of modern statistical software. The utility of mixture models are explained in detail using a numerical example.

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

DATA AVAILABILITY STATEMENT

The data used in the numerical example were simulated as indicated in Section 6. The data are available from the corresponding author upon reasonable request.

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