Linearity assessment: deviation from linearity and residual of linear regression approaches

Author:

Lim Chun Yee1,Lee Xavier1,Tran Mai Thi Chi23,Markus Corey4ORCID,Loh Tze Ping5,Ho Chung Shun6,Theodorsson Elvar7,Greaves Ronda F.89ORCID,Cooke Brian R.10,Zakaria Rosita1112

Affiliation:

1. Engineering Cluster , Singapore Institute of Technology , Singapore , Singapore

2. Faculty of Medical Technology , Hanoi Medical University , Hanoi , Vietnam

3. Department of Clinical Biochemistry , National Children’s Hospital , Hanoi , Vietnam

4. Flinders University International Centre for Point-of-Care Testing, Flinders Health and Medical Research Institute , Adelaide , Australia

5. Department of Laboratory Medicine , National University Hospital , Singapore , Singapore

6. Biomedical Mass Spectrometry Unit, Department of Chemical Pathology , The Chinese University of Hong Kong, Prince of Wales Hospital , Shatin , NT , Hong Kong

7. Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology , Linkoping University , Linkoping , Sweden

8. Department of Paediatrics , The University of Melbourne , Parkville , VIC , Australia

9. Victorian Clinical Genetics Services , Murdoch Children’s Research Institute , Parkville , VIC , Australia

10. Department of Clinical Biochemistry, PathWest Laboratory Medicine , Fiona Stanley Hospital , Murdoch , Western Australia

11. School of Health and Biomedical Sciences , RMIT University , Melbourne , VIC , Australia

12. Murdoch Children’s Research Institute , Parkville , VIC , Australia

Abstract

Abstract In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development.

Publisher

Walter de Gruyter GmbH

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