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Sample Size and Non-Inferiority Margin for Vaccine Efficacy Trials

Source: R/ss_ni_ve.R
ss_ni_ve.Rd

Computes the non-inferiority margin, number of events, and maximum hazard ratio (HR) to declare non-inferiority in vaccine efficacy (VE) trials, based on the approach described by Fleming et al. (2021).

Usage

ss_ni_ve(ve_lci, alpha = 0.025, power = 0.9, use70 = FALSE, preserve = 0.5)

Arguments

ve_lci

Numeric. Lower bound of the current vaccine's efficacy (e.g., 0.95 for 95% VE).

alpha

Numeric. Type I error rate (default = 0.025).

power

Numeric. Desired power for the test (default = 0.90).

use70

Logical. If TRUE, assumes at least 30% VE for the new vaccine (the 90–70 rule); otherwise, preserves a fixed fraction of the reference VE.

preserve

Numeric. Proportion of the current vaccine's efficacy to preserve under use70 = FALSE (default = 0.5).

Value

A named list with:

  • Upper limit of the HR used to estimate the sample size: Hazard ratio corresponding to ve_lci.

  • Non-inferior margin in HR scale: Non-inferiority margin expressed as a hazard ratio.

  • Alpha: The type I error used.

  • Power: The power used.

  • Total number of events: Total number of events required in the trial.

  • Max HR to declare NI: Maximum observed hazard ratio that satisfies the non-inferiority criterion.

  • Max number of events in the experimental group: Maximum number of events in the experimental group still compatible with non-inferiority.

  • Non-inferior criteria: Description of the applied non-inferiority rule ("At least 30% VE" or "or preserved effect").

Details

The method applies either the 95–95 rule or 90–70 rule, depending on whether a minimum VE of 30% is assumed (use70 = TRUE) or 50% of the current VE is preserved.

This implementation approximates Table 1 of the paper using exact binomial confidence intervals via binom.test and the nBinomial1Sample function from gsDesign.

References

Fleming, T.R., Powers, J.H., & Huang, Y. (2021). The use of active controls and non-inferiority studies in evaluating COVID-19 vaccines. Clinical Trials, 18(3), 335–342. doi:10.1177/1740774520988244

Examples

ss_ni_ve(ve_lci = 0.95)
#> $`Upper limit of the HR used to estimate the sample size`
#> [1] 0.05
#> 
#> $`Non-inferior margin in HR scale`
#> [1] 4.472136
#> 
#> $Alpha
#> [1] 0.025
#> 
#> $Power
#> [1] 0.9
#> 
#> $`Total number of events`
#> [1] 28
#> 
#> $`Max HR to declare NI`
#> [1] 1.8
#> 
#> $`Max number of events in the experimental group`
#> [1] 18
#> 
#> $`Non-inferior criteria`
#> [1] "Preserve at least 50% of the VE in the new vaccine"
#>