Diurnal and racial variance of white blood cell parameters in early phase clinical trials: a retrospective analysis of pooled data from multiple phase I trials

[Speaker] Jorg Taubel:1,2
[Co-author] Jonathan Bowen:1, Daniela Cimmaruta:3, Dilshat Djumanov:1, Ulrike Lorch:1, Simon Coates:1, Georg Ferber:4
1:Richmond Pharmacology, St Georges University of London, UK, 2:St. George's University of London, UK, 3:Department of Experimental Medicine, Second University of Naples, Italy, 4:Statistik Georg Ferber GmbH, 4125 Riehen, Switzerland

BACKGROUND: The circulating white blood cell count is a common inclusion criterion for clinical studies. Generally the thresholds for these values are not defined by the time of day that samples are obtained nor do they vary by the ethnic group from which the subjects are recruited. We have characterised the variance in circulating white cell levels when categorised by time of day and self-ascribed racial group in early phase clinical trials involving healthy adult volunteers.
METHODS: White blood-cell parameters were obtained from N phase-I clinical trial studies. Subjects were grouped by race ascription; Asian, Black (Black African & Black Caribbean), or Caucasian. Subjects belonging to other groups are not considered here. The samples were further grouped by time-of-day of phlebotomy. Pooled data obtained from 12,586 blood samples from 7157 healthy men and women was analysed.
RESULTS: Results show clear and statistically significant rises in Total White Cell [Figure 1], and sub population counts (Neutrophils, Monocytes and Basophils) between 07:00 and 18:00 when categorized by ethnicity. Results also verify a diurnal pattern of white cell counts. Counts of total WBC, neutrophils, basophils and monocytes from Caucasian and Asian samples were consistently higher than from Black subjects.
Total WBC counts (44%) as well as neutrophil (67%), lymphocyte (30%) and monocyte (13%) counts showed increases over the day. The counts for eosinophils fell (-20%) while basophils showed no change.
CONCLUSION: Consideration of ethnic ascription and sampling time of day should be taken into account when interpreting white cell levels, particularly in subjects who are Black African or Black Caribbean and may show benign ethnic neutropenia. Considerations should be made with respect to the design and implementation of trial inclusion criteria, as well as in the assessment of adverse events, including the relationship to the investigational product and their grading.

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