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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.
Guoqiao
G
Wang
Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Gary R
GR
Cutter
Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Stacey S
SS
Cofield
Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Fred
F
Lublin
McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jerry S
JS
Wolinsky
Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Tarah
T
Gustafson
Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Stephen
S
Krieger
Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.
Amber
A
Salter
D000293:Adolescent; D000328:Adult; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000068556:Interferon beta-1a / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012107:Research Design / Q000706:statistics & numerical data; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate; D000068556:Interferon beta-1a
Expanded Disability Status Scale; Multiple sclerosis; confirmed disability progression rate; relapsing-remitting multiple sclerosis
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