Abstract
It is widely accepted that, due to the small size of first-in-human (FIH) trials, safety signals are difficult to detect. The chances of detecting early signals in cardiovascular safety, including heart rate, blood pressure, QT prolongation, etc., have long been considered to be remote. However, much of this belief is based on an analysis involving pair-wise comparisons of very small cohorts. When dose is considered as a continuous variable, dose–response becomes the main focus and power can be significantly improved with appropriate testing procedures. In this research, we try to quantify through simulations the power in this setting and demonstrate that cardiovascular safety signals in general have reasonable statistical power for early detection when using a dose–response analysis. The simulations account for different magnitudes of effects and various scenarios including linear, log-linear, and Emax relationships between dose and safety signal, together with multiple parametric and nonparametric tests.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Hollander, M. and Wolfe, D. A.: Nonparametric Statistical Methods, pp.120-123. Wiley, New York (1973)
Kotz, S., Read, C. B., Blakrishnan, N., and Vidakovic, Brani. (eds): Encyclopedia of Statistical Sciences 2nd Edition, Volume 9, pp. 5811-14. Wiley, New York (2006)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this paper
Cite this paper
Wang, O., Hale, M., Huang, J. (2013). Statistical Power to Detect Cardiovascular Signals in First-in-Human Trials: Is It Really Small?. In: Hu, M., Liu, Y., Lin, J. (eds) Topics in Applied Statistics. Springer Proceedings in Mathematics & Statistics, vol 55. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7846-1_23
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7846-1_23
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-7845-4
Online ISBN: 978-1-4614-7846-1
eBook Packages: Mathematics and StatisticsMathematics and Statistics (R0)