Sains Malaysiana 52(5)(2023): 1581-1593

http://doi.org/10.17576/jsm-2023-5205-19

Identifying Outlier Subjects in Bioavailability Trials Using Generalized Studentized Residuals

(Pengenalpastian Subjek Outlier dalam Ujian Ketersediaan Biologi Menggunakan Residu Terstuden)

F.P. LIM^1,*, L.L. WONG², H.K. YAP³ & K.S. YOW⁴

^1,2,4Department of Mathematics and Statistics, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

³Department of Mathematical and Actuarial Sciences, Lee Kong Chian Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Sungai Long Campus, Bandar Sungai Long, Cheras, 43000 Kajang, Selangor Darul Ehsan, Malaysia

Received: 19 August 2022/Accepted: 10 May 2023

Abstract

This paper discusses several outlier detection methods for bioavailability trials, particularly based on residuals. By considering a simplified model of standard crossover model, which is commonly used in bioavailability trials, we propose an outlier detection procedure based on the generalized studentized residuals (SR3) and compare its ability of detecting the possible outlying subjects with two existing procedures, which are carried out based on the classical studentized residual (SR1) and studentized residual using median absolute deviation (SR2). The performances of these procedures in detecting outlying subject are presented via an extensive simulation study. The results show that the proposed procedure SR3 performs more powerful than that using SR1, and as well as the procedure using SR2 for outlier detection. As an illustration, these procedures are implemented on a real dataset from bioavailability study, namely, the area under the curve (AUC) dataset for two erythromycin formulations.

Keywords: Bioavailability; crossover design; generalized studentized residuals; outlier; residual

Abstrak

Kertas ini membincangkan beberapa kaedah pengesanan titik terpencil untuk ujian bioketersediaan, terutamanya berdasarkan residu. Dengan mempertimbangkan satu model silang piawai yang biasa digunakan dalam ujian bioketersediaan, kami mencadangkan satu prosedur pengesanan titik terpencil berdasarkan residu terstuden teritlak (SR3) dan membandingkan keupayaannya untuk mengesan kemungkinan subjek terpencil dengan dua prosedur sedia ada, iaitu dijalankan berdasarkan residu terstuden klasik (SR1) dan residu terstuden yang menggunakan sisihan mutlak median (SR2). Prestasi prosedur berkenaan dalam mengesan subjek terpencil dibentangkan melalui kajian simulasi yang ekstensif. Keputusan menunjukkan bahawa prosedur yang dicadangkan SR3 berprestasi lebih baik daripada prosedur yang menggunakan SR1, dan juga prosedur menggunakan SR2 bagi pengesanan titik terpencil. Sebagai ilustrasi, prosedur tersebut dilaksanakan pada satu set data sebenar daripada kajian bioketersediaan, iaitu, luas di bawah lengkungan (AUC) set data untuk dua formulasi eritromisin.

Kata kunci: Bioketersediaan; pencilan; reka bentuk silang; residu terstuden teritlak; residu

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^*Corresponding author; email: fongpeng@upm.edu.my