Determining the validity of hospital laboratory reference intervals for healthy young adults participating in early clinical trials of candidate vaccines

Abstract

This was a retrospective study to determine the validity of institutional reference intervals for interpreting biochemistry and hematology results in healthy adults in the context of clinical trials of preventive vaccines. An example population of 974 healthy adults participating in clinical trials at the Jenner Institute, Oxford, UK, between 1999 and 2009 was studied. Methods for calculating the central 95% ranges and determining the coefficients of within person variation were demonstrated. Recommendations have been made as to how these data can be usefully applied to the interpretation of blood results in healthy adult subjects for the purposes of clinical trial inclusion decisions and post-vaccination safety monitoring.

Keywords: :

• healthy young adult subjects
• clinical trials
• candidate vaccines
• haematological and biochemical reference intervals
• pre-and post-intervention safety analysis

Disclosure of Potential Conflicts of Interest

HM, SCG and AVSH are named inventors on a composition of matter patent for MVA85A, and are shareholders in a Joint Venture formed for the further development of this vaccine. HM, AVSH, SCG and GO are named as inventors on patent applications relating to induction of T-cell responses by vaccination.

Acknowledgments

We are grateful to all the subjects who volunteered to participate in clinical trials and to members of the clinical trial teams who performed recruitment and screening procedures.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The Jenner Institute clinical trials unit receives general research support funding from the UK National Institute for Health Research Oxford Biomedical Research Centre. Funders for specific clinical trials for which subjects were recruited are acknowledged in the cited publications. H.M. is a Wellcome Trust Senior Clinical Research Fellow. H.M., S.C.G. and A.V.S.H. are Jenner Institute Investigators. The funding agencies took no part in study design, data analysis, manuscript preparation or decision to publish.

Notes

† These authors contributed equally to this work.