The BACH project protocol: an international multicentre total Bile Acid Comparison and Harmonisation project and sub-study of the TURRIFIC randomised trial

Corey Markus; Suzette Coat; Hanns-Ulrich Marschall; Catherine Williamson; Peter Dixon; Maria Fuller; Susan Matthews; Wayne Rankin; Michael Metz; William M. Hague

doi:10.1515/cclm-2021-0496

Article

The BACH project protocol: an international multicentre total Bile Acid Comparison and Harmonisation project and sub-study of the TURRIFIC randomised trial

Corey Markus , Suzette Coat , Hanns-Ulrich Marschall , Catherine Williamson , Peter Dixon , Maria Fuller , Susan Matthews , Wayne Rankin , Michael Metz and William M. Hague

Published/Copyright: August 6, 2021

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 12

Abstract

Objectives

Multicentre international trials relying on diagnoses derived from biochemical results may overlook the importance of assay standardisation from the participating laboratories. Here we describe a study protocol aimed at harmonising results from total bile acid determinations within the context of an international randomised controlled Trial of two treatments, URsodeoxycholic acid and RIFampicin, for women with severe early onset Intrahepatic Cholestasis of pregnancy (TURRIFIC), referred to as the Bile Acid Comparison and Harmonisation (BACH) study, with the aims of reducing inter-laboratory heterogeneity in total bile acid assays.

Methods

We have simulated laboratory data to determine the feasibility of total bile acid recalibration using a reference set of patient samples with a consensus value approach and subsequently used regression-based techniques to transform the data.

Results

From these simulations, we have demonstrated that mathematical recalibration of total bile acid results is plausible, with a high probability of successfully harmonising results across participating laboratories.

Conclusions

Standardisation of bile acid results facilitates the commutability of laboratory results and collation for statistical analysis. It may provide the momentum for broader application of the described techniques in the setting of large-scale multinational clinical trials dependent on results from non-standardised assays.

Keywords: bile acid; cholestasis; comparison; computer simulation; harmonisation; pregnancy; protocol; quality assurance

Dedicated to the Memory of Dr Michael Metz. It is with great sadness that we dedicate this manuscript to the memory of the late Dr Michael Metz, whom many will have known through his international activities in the field of paediatric and obstetric clinical chemistry. Michael was incredibly passionate about paediatric and obstetric laboratory medicine and was highly regarded for his commitment to patient care and teaching. The genesis of this harmonisation project arose from his interest in the medicine of ICP. Michael was an active committee member and chaired the South Australian/Northern Territory Australasian Association of Clinical Biochemists (AACB) branch for over 10 years, while internationally he was an elected member of the International Federation of Clinical Chemistry: Task Force on Paediatric Laboratory Medicine. He was a member of the advisory board of the Atherosclerosis Australasia Familial Hypercholesterolaemia Registry and sole consultant for the lipid clinic at the Adelaide Women’s and Children’s Hospital. Michael was also known for his warm generous nature and sense of humour. Michael is profoundly missed by all his colleagues and friends. Vale Michael!

Corresponding author: Corey Markus, Automated Laboratory, SA Pathology, GPO Box 2100, Adelaide, SA, 5001, Australia; and Flinders University International Centre for Point-of-Care Testing, Flinders Health and Medical Research Institute, Sturt Road, Bedford Park, SA, 5042, Australia, Email: corey.markus@flinders.edu.au

Michael Metz deceased

Funding source: Australasian Association of Clinical Biochemists (AACB)

Acknowledgments

We gratefully acknowledge the Australasian Association of Clinical Biochemists (AACB) in agreeing to provide financial support for transportation of BACH samples to participating laboratories servicing Australian TURRIFIC trial recruitment sites.

Research funding: None declared.
Author contributions: MM, WH, MF and CM conceived the requirement for harmonisation of total bile acids. CM, WR, SM and WH were involved in the experimental design and questionnaire. CM performed the simulation, summary statistical results and produced the graphical output. WH, SC, H-UM and CW are contributing to subject recruitment for the TURRIFIC study and, together with PD, are providing linkage to participating international laboratories. CM drafted the original manuscript. All authors have read and approved the final manuscript.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals providing samples for this study.
Ethical approval: Ethical approval for the study has been granted by the Women’s and Children’s Hospital Human Research Ethics Committee (HREC/18/WCHN/36).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0496).

Received: 2021-04-26

Accepted: 2021-06-22

Published Online: 2021-08-06

Published in Print: 2021-11-25

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Keywords for this article

bile acid; cholestasis; comparison; computer simulation; harmonisation; pregnancy; protocol; quality assurance