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Licensed Unlicensed Requires Authentication Published by De Gruyter February 12, 2020

A continued method performance monitoring approach for the determination of pediatric renin samples – application within a European clinical trial

Martin Feickert, Ilja Burdman, Nina Makowski, Mohsin Ali, Anke Bartel, Bjoern B. Burckhardt ORCID logo and on behalf of the LENA consortium

Abstract

Background

Plasma renin levels were determined in the academia-driven, EU-funded “Labeling of Enalapril from Neonates up to Adolescents” (LENA) project to evaluate its role in pediatric heart failure. Quality-controlled bioanalysis is crucial to ensure reliable data generation. However, a comprehensive bioanalytical quality control (QC) concept to monitor the method performance within an academic environment was lacking.

Methods

Thus, a QC concept was designed encompassing regulatory guidance, international recommendations and current scientific discussions. The concept included (1) a system-suitability test, (2) verification of single bioanalytical runs by calibration curve performance and evaluation of QCs, (3) assessment of the inter-run accuracy according to Clinical Laboratory Standards Institute (CLSI) guideline, (4) monitoring of reproducibility by pediatric incurred samples, (5) blank-sample analysis and (6) participation in interlaboratory testing.

Results

The concept was successfully applied to the academic project. About 11% of single runs were identified as invalid and triggered a re-analysis of unknown samples being included in those runs. The usefulness of the customized inter-run monitoring was demonstrated and proved the good accuracy from the first to the last run. All 147 reanalyzed incurred sample pairs complied with regulatory requirements.

Conclusions

The regulatory complied QC concept was customized for the demands of academia-driven pediatric trials and contributed to the reliable quantification of 965 pediatric renin samples.


Corresponding author: Bjoern B. Burckhardt, PhD, Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Universitaetsstr. 1, 40225 Dusseldorf, Germany, Phone: +49 211 81 10745, Fax: +49 211 81 10741

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602295 (LENA), Funder Id: http://dx.doi.org/10.13039/100011272.

  3. Employment or leadership: The authors M. Feickert, I. Burdman, N. Makowski and M. Ali were financially supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602295 (LENA). The author B.B. Burckhardt was head of bioanalysis within the LENA project.

  4. Honorarium: None declared

  5. Competing interests: The funding organization played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2019-11-10
Accepted: 2019-12-23
Published Online: 2020-02-12
Published in Print: 2020-10-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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