CI.RatioF: 1-2*alpha Fieller CI given point estimate, CV (, CVb) and n

In PowerTOST: Power and Sample Size for (Bio)Equivalence Studies

1–2*alpha Fieller CI given point estimate, CV (, CVb) and n

Description

Utility function to calculate the 1–2α Fieller confidence interval given the point estimate, CV (, CVb), and n for the parallel group and 2×2 crossover.

Usage

CI.RatioF(alpha = 0.025, pe, CV, CVb, n, design = c("2x2", "parallel"))

Arguments

alpha	Type I error probability, aka significance level. Defaults here to 0.025 because this function is intended for studies with clinical endpoints.
pe	Point estimate of T/R ratio.
CV	Coefficient of variation as ratio (not percent). In case of design="parallel" this is the CV of the total variability, in case of design="2x2" the intra-subject CV.
CVb	CV of the between-subject variability. Only necessary for design="2x2".
n	Total number of subjects if a scalar is given. Number of subjects in (sequence) groups if given as vector.
design	A character string describing the study design. design="parallel" or design="2x2" allowed for a parallel two-group design or a classical TR|RT crossover design.

Details

The CV(within) and CVb(etween) in case of design="2x2" are obtainedvia an appropriate ANOVA from the error term and from the difference (MS(subject within sequence)-MS(error))/2.

Value

Returns the 1–2α confidence interval.

Note

The function assumes an evaluation using un-transformed data.
The function assumes equal variances in case of design="parallel".
The formula implemented covers balanced and unbalanced designs.

Note that when the mean of the denominator of the ratio is close to zero, confidence intervals might be degenerated and are returned as NA. In such a case a warning is issued.

Whether the function vectorizes properly is not thoroughly tested.

This function is intended for studies with clinical endpoints. In such studies the 95% confidence intervals are usually used for equivalence testing. Therefore, alpha defaults here to 0.025 (see EMA 2000).

Author(s)

D. Labes

References

Locke CS. An exact confidence interval from untransformed data for the ratio of two formulation means. J Pharmacokin Biopharm. 1984;12(6):649–55. \Sexpr[results=rd]{tools:::Rd_expr_doi("10.1007/BF01059558")}

Hauschke D, Steinijans VW, Pigeot I. Bioequivalence Studies in Drug Development. Chichester: John Wiley; 2007. Chapter 10. \Sexpr[results=rd]{tools:::Rd_expr_doi("10.1002/9780470094778.fmatter")}

European Medicines Agency, Committee for Proprietary Medicinal Products. Points to consider on switching between superiority and non-inferiority. London, 27 July 2000. CPMP/EWP/482/99

See Also

CI.BE, power.RatioF

Examples

# 95% Fieller CI for the 2x2 crossover
CI.RatioF(pe = 0.95, CV = 0.3, CVb = 0.6, n = 32)

PowerTOST documentation built on May 29, 2024, 4:40 a.m.