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A Meta-Analysis of Adverse Events in the Phase I Clinical Trials Conducted at Fortrea Leeds Clinical Research Unit from 2016 to 2021.
  • Alicia Barton,
  • Oren Cohen,
  • Jim Bush
Alicia Barton
University of Leeds Faculty of Biological Sciences

Corresponding Author:alicia.barton@hotmail.co.uk

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Oren Cohen
Fortrea Drug Development
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Jim Bush
Fortrea Drug Development
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Abstract

Aim Tragic incidents in Phase I trials have been cited to suggest that trials put participants at high levels of risk. This meta-analysis aimed to evaluate risks to Phase I trial participants at the Fortrea Clinical Research Unit (FCRU) (UK) between 2016-2021. Methods Sixty-Five FCRU Phase I trials enrolling 3194 participants were included (99% healthy volunteers). Analysed trials tested active drugs, had finalised clinical study reports (CSRs), and standardised AE reporting procedures. Data on drug type, study design, participant numbers, and AEs were extracted from CSRs. A chi-square test of homogeneity tested mild, moderate, and severe AE probability distributions between placebo and active groups. A negative binomial regression examined relationships of administration route (parenteral vs non-parenteral), drug type (small molecule vs biologic), and trial type (First in Human (FIH) vs non-FIH) to number of AEs reported. Results Over 55% of participants reported at least one AE. 5051 AEs were reported; classified as mild (90.1%), moderate (9.4%), severe (0.4%), or unknown (0.1%). Proportion of AEs by severity category was similar between active and placebo groups (χ2(2)=3.942, p=0.139). Fifteen serious AEs were reported. Parenteral administration and biological drugs had no significant effect on AE incidence. FIH trials were a significant predictor of lower AE risk. Conclusion AEs were commonly reported in these Phase I trials. Trial features perceived to increase AE risks (parenteral administration, biologic drugs) did not and AE risk in FIH trials was lower compared with non-FIH trials. The trials analysed posed a low risk of serious harm to participants.
Submitted to British Journal of Clinical Pharmacology
28 Feb 2024Reviewer(s) Assigned
22 Apr 2024Review(s) Completed, Editorial Evaluation Pending
24 Apr 2024Editorial Decision: Revise Major