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Noninferiority trial designs for odds ratios and risk differences
Author(s) -
Hilton Joan F.
Publication year - 2010
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3846
Subject(s) - sample size determination , odds ratio , statistics , mathematics , null hypothesis , type i and type ii errors , scale (ratio) , confidence interval , value (mathematics) , odds , statistical power , econometrics , combinatorics , logistic regression , physics , quantum mechanics
This study presents constrained maximum likelihood derivations of the design parameters of noninferiority trials for binary outcomes with the margin defined on the odds ratio ( ψ ) or risk‐difference ( δ ) scale. The derivations show that, for trials in which the group‐specific response rates are equal under the point‐alternative hypothesis, the common response rate, π N , is a fixed design parameter whose value lies between the control and experimental rates hypothesized at the point‐null, { π C , π E }. We show that setting π N equal to the value of π C that holds under H 0 underestimates the overall sample size requirement. Given { π C , ψ } or { π C , δ } and the type I and II error rates, or algorithm finds clinically meaningful design values of π N , and the corresponding minimum asymptotic sample size, N = n E + n C , and optimal allocation ratio, γ = n E / n C . We find that optimal allocations are increasingly imbalanced as ψ increases, with γ ψ <1 and γ δ ≈1 /γ ψ , and that ranges of allocation ratios map to the minimum sample size. The latter characteristic allows trialists to consider trade‐offs between optimal allocation at a smaller N and a preferred allocation at a larger N . For designs with relatively large margins (e.g. ψ >2.5), trial results that are presented on both scales will differ in power, with more power lost if the study is designed on the risk‐difference scale and reported on the odds ratio scale than vice versa. Copyright © 2010 John Wiley & Sons, Ltd.