A modified Wald test for reference scaled assessment of analytical equivalence.
For the reference scaled equivalence hypothesis to reduce the deficiency of the current practice in analytical equivalence assessment, the Wald test with Constrained Maximum Likelihood Estimate (CMLE) of the standard error was proposed to improve the efficiency when the sample sizes of test and reference product lots are small, and variances are unequal. However, by using the Wald test with CMLE standard error, simulations show that the type I error rate is below the nominal significance level. We proposed the Modified Wald test with CMLE standard error by replacing the maximum likelihood estimate of reference standard deviation with the sample estimate (MWCMLE), resulting in further improvement of type I error rate and power over the Wald test with CMLE standard error. In this paper, we further compare the proposed MWCMLE method to the Exact-test-Based (EB) method and the Generalized Pivotal Quantity (GPQ) method with equal or unequal variances, or equal or unequal sample sizes of both product lots. The simulations show that the proposed MWCMLE method outperforms the other two methods in type I error rate control and power improvement.
['Weng|Yu-Ting|YT|', 'Tsong|Yi|Y|', 'Shen|Meiyu|M|', 'Wang|Chao|C|']
D002986:Clinical Trials as Topic D003198:Computer Simulation D016001:Confidence Intervals D018592:Cross-Over Studies D023381:Endpoint Determination D006801:Humans D016013:Likelihood Functions D015233:Models, Statistical D018401:Sample Size D016008:Statistical Distributions D013810:Therapeutic Equivalency
Wald tests analytical equivalence constrained maximum likelihood estimate GPQ Equivalence tests exact-based test