April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Power and Sample Size Calculations for Primary Open Angle Glaucoma / Ocular Hypertension Clinical Trials Accounting for Correlation of Measures among the Time Points across Visits
Author Affiliations & Notes
  • Dale W Usner
    Statistics, Statistics and Data Corporation, Tempe, AZ
  • Richard Abelson
    Statistics, Statistics and Data Corporation, Tempe, AZ
  • Footnotes
    Commercial Relationships Dale Usner, Statistics and Data Corporation (E); Richard Abelson, Statistics and Data Corporation (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 535. doi:https://doi.org/
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      Dale W Usner, Richard Abelson; Power and Sample Size Calculations for Primary Open Angle Glaucoma / Ocular Hypertension Clinical Trials Accounting for Correlation of Measures among the Time Points across Visits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):535. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: A general strategy for showing non-inferiority of a test product, to an existing approved product, is to demonstrate the following efficacy criteria: the upper limit of a 95% confidence interval (CI) around the difference in IOP: test product - approved product is: a) < 1.5 mm Hg at all defined time points b) < 1.0 mm Hg at a majority of time points Historically, 1) the correlation among time points within a subject/eye and 2) the requirement of a majority of time points having an upper 95% CI < 1 mm Hg have not been overtly used when determining sample size and power. We propose a method to account for both of these points.

Methods: Multivariate normal distributions with varying assumptions around the sample size, mean differences, variances, and correlations were used; where correlations ranged from 40% to 70% as estimated from historic data. 500,000 random samples were created and 95% CIs calculated. Power was calculated as the proportion of random samples showing the upper limit of the 95% CI < 1.5 mm Hg, with a majority < 1.0 mm Hg.

Results: Power calculations from common methods either over estimate the required sample size (calculations assuming all 95% CIs must be < 1.0 mm Hg) or under estimate the required sample size (calculations assuming only that all 95% CIs < 1.5 mm Hg). The amount of the over estimation and under estimation depend on the assumed correlation among time points; the higher the correlation the less the over estimation and the more the under estimation of sample size.

Conclusions: When determining power and sample size for primary open angle glaucoma / ocular hypertension clinical trials, neglecting to account for the complete efficacy criteria and the correlation among time points will result in the trial requiring too many subjects/eyes or having too low power.

Keywords: 459 clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • 568 intraocular pressure  
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