caa a22 4500 445809175 CHVBK 20180317145206.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00415-011-6021-1 doi (NATIONALLICENCE)springer-10.1007/s00415-011-6021-1 Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies [Elektronische Daten] [Brian Healy, Tanuja Chitnis, David Engler] In patients with multiple sclerosis, investigation of a treatment effect on disease progression in clinical trials and observational studies often uses sustained progression on the expanded disability status scale (EDSS) as an outcome. It is not clear whether this outcome is the most powerful to detect a treatment effect on clinical disease progression. Assessment of EDSS modeling choice on the detection of treatment effect was of interest. This assessment was separately conducted under three potential treatment effects: treatment reducing the chance of higher future EDSS, treatment increasing the chance of lower future EDSS, and treatment leading to both effects. To assess the effect of modeling choice, nine modeling strategies were applied to the data to determine the most powerful approach. EDSS measurements were simulated at 6month intervals for 24months. Each patient's initial EDSS value ranged between 0 and 3, and probabilities of transitioning from one EDSS state to another were based on the empirical probabilities of transition obtained from available clinical data. Modeling approaches based on sustained progression had less power than approaches which modeled the EDSS score directly, regardless of treatment effect. This difference was especially pronounced when the treatment effect corresponded to an increase in the probability of improvement. Sustained progression on the EDSS is a less powerful outcome measure for clinical progression than approaches based on the actual EDSS values. Springer-Verlag, 2011 Clinical trials nationallicence Disease progression nationallicence Multiple sclerosis nationallicence Sample size calculations nationallicence Healy Brian Partners MS Center, Brigham and Women's Hospital, 1 Brookline Place Suite 602, 02445, Brookline, MA, USA aut Chitnis Tanuja Partners MS Center, Brigham and Women's Hospital, 1 Brookline Place Suite 602, 02445, Brookline, MA, USA aut Engler David Department of Statistics, 230 TMCB Brigham Young University, 84602, Provo, UT, USA aut Journal of Neurology Springer-Verlag 258/10(2011-10-01), 1812-1819 0340-5354 258:10<1812 2011 258 415 https://doi.org/10.1007/s00415-011-6021-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-6021-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Healy Brian Partners MS Center, Brigham and Women's Hospital, 1 Brookline Place Suite 602, 02445, Brookline, MA, USA aut NATIONALLICENCE 700 1- Chitnis Tanuja Partners MS Center, Brigham and Women's Hospital, 1 Brookline Place Suite 602, 02445, Brookline, MA, USA aut NATIONALLICENCE 700 1- Engler David Department of Statistics, 230 TMCB Brigham Young University, 84602, Provo, UT, USA aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/10(2011-10-01), 1812-1819 0340-5354 258:10<1812 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer