Baseline EDSS proportions in MS clinical trials affect the overall outcome and power: A cautionary note

In randomized clinical trials, when treatments do not work equally effectively across stratifications of participants, observed event rates may differ from those hypothesized leading to deviations in estimated power.

To investigate the effect of distributions of baseline Expanded Disability Status Scale (EDSS) proportions in relapsing-remitting multiple sclerosis (RRMS) on the trial outcome, confirmed disability progression rate (CDPR), and power.

We reported CDPRs in the CombiRx trial by baseline EDSS and by groups (1st (0, 1), 2nd (1.5, 2), 3rd (2.5, 3), and 4th (⩾3.5)) and investigated the effect of different combinations of baseline EDSS proportions on the trial outcome and power.

There were 244 (25.4%) participants in the 1st group, 368 (38.4%) in the 2nd group, 223 (23.3%) in the 3rd group, and 124 (12.9%) in the 4th group with CDPRs of 40.1%, 13.9%, 11.2%, and 16.9%, respectively. Both CDPR and power increased when the proportion of the 1st group increased in hypothetical trials with equal sample sizes in each arm, and a 10% increase in the 1st group led to a 5% increase in power.

Various baseline EDSS proportions yielded different CDPRs and power, suggesting caution in interpretation of treatment effects across trials that enrolled participants with different proportions of baseline EDSS.