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Table 1.

Clinical scenarios considered in the simulation study

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Table 2.

The effect size based on a total sample size of N patients, a 5% significance level, balanced allocation across K strata, m independent endpoint components and 80% power of the stratified WL test

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Table 2 Expand

Fig 1.

Impact of allocation bias in stratified clinical trials with multi-component endpoints evaluated using the stratified WL test.

The T1Es under misspecification calculated for samples of randomization lists generated by different RPs in clinical trials with N = 32 patients, K balanced strata, m standard normally distributed uncorrelated endpoints and common allocation bias effect for all and chosen as proportion of the effect sizes , , and .

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Fig 2.

Impact of allocation bias on the test decisions of the stratified WL test depending on the sample size and the number of strata.

T1Es under misspecification calculated for samples of randomization lists generated by different RPs in clinical trials with patients, balanced strata, m = 2 standard normally distributed uncorrelated endpoints and common allocation bias effect for all and with and .

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Fig 3.

Impact of allocation bias on the test decisions of the stratified WL test for increasing number of endpoint components aggregated into the multi-component endpoint.

Mean misspecified T1Es calculated for samples of randomization lists generated by different RPs in clinical trials with N = 32 patients, K = 2 balanced strata, standard normally distributed uncorrelated endpoints and common allocation bias effect for all and with .

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Fig 3 Expand

Fig 4.

Impact of allocation bias on the test decisions of the stratified WL test for correlated endpoint components aggregated into the multi-component endpoint.

Misspecified T1Es calculated for samples of randomization lists generated by different RPs in clinical trials with N = 32 patients, K = 2 balanced strata, m = 4 correlated normally distributed uncorrelated endpoints and common allocation bias effect for and with . All endpoint components are equally correlated by the factor .

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Fig 4 Expand

Table 3.

Key lessons learned for mitigating allocation bias in small sample stratified clinical trials with multi-component endpoints that are evaluated using the WL test.

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Table 3 Expand