Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies

被引:9
作者
Healy, Brian [1 ,2 ]
Chitnis, Tanuja [1 ]
Engler, David [3 ]
机构
[1] Brigham & Womens Hosp, Partners MS Ctr, Brookline, MA 02445 USA
[2] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA
[3] 230 TMCB Brigham Young Univ, Dept Stat, Provo, UT 84602 USA
关键词
Clinical trials; Disease progression; Multiple sclerosis; Sample size calculations; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INTERFERON BETA-1A; CLINICAL-TRIALS; RELAPSE RATE; DISABILITY; MULTICENTER; NATALIZUMAB; MRI; MS;
D O I
10.1007/s00415-011-6021-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 6 month intervals for 24 months. 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.
引用
收藏
页码:1812 / 1819
页数:8
相关论文
共 29 条
[1]  
Agresti A, 2013, Categorical data analysis, V3rd
[2]   Nonparametric two-sample comparisons of changes on ordinal responses [J].
Bajorski, P ;
Petkau, J .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1999, 94 (447) :970-978
[3]   A simple sample size formula for analysis of covariance in randomized clinical trials [J].
Borm, George F. ;
Fransen, Jaap ;
Lemmens, Wim A. J. G. .
JOURNAL OF CLINICAL EPIDEMIOLOGY, 2007, 60 (12) :1234-1238
[4]   How effective are disease-modifying drugs in delaying progression in relapsing-onset MS? [J].
Brown, M. G. ;
Kirby, S. ;
Skedgel, C. ;
Fisk, J. D. ;
Murray, T. J. ;
Bhan, V. ;
Sketris, I. S. .
NEUROLOGY, 2007, 69 (15) :1498-1507
[5]  
Coles AJ, 2008, NEW ENGL J MED, V359, P1786, DOI 10.1056/NEJMoa0802670
[6]   A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis [J].
Cudkowicz, ME ;
Shefner, JM ;
Schoenfeld, DA ;
Brown, RH ;
Johnson, H ;
Qureshi, M ;
Jacobs, M ;
Rothstein, JD ;
Appel, SH ;
Pascuzzi, RM ;
Heiman-Patterson, TD ;
Donofrio, PD ;
David, WS ;
Russell, JA ;
Tandan, R ;
Pioro, EP ;
Felice, KJ ;
Rosenfeld, J ;
Mandler, RN ;
Sachs, GM ;
Bradley, WG ;
Raynor, EM ;
Baquis, GD ;
Belsh, JM ;
Novella, S ;
Goldstein, J ;
Hulihan, J .
NEUROLOGY, 2003, 61 (04) :456-464
[7]   INTERFERON BETA-1B IS EFFECTIVE IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS - CLINICAL-RESULTS OF A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL [J].
DUQUETTE, P ;
GIRARD, M ;
DESPAULT, L ;
DUBOIS, R ;
KNOBLER, RL ;
LUBLIN, FD ;
KELLEY, L ;
FRANCIS, GS ;
LAPIERRE, Y ;
ANTEL, J ;
FREEDMAN, M ;
HUM, S ;
GREENSTEIN, JI ;
MISHRA, B ;
MULDOON, J ;
WHITAKER, JN ;
EVANS, BK ;
LAYTON, B ;
SIBLEY, WA ;
LAGUNA, J ;
KRIKAWA, J ;
PATY, DW ;
OGER, JJ ;
KASTRUKOFF, LF ;
MOORE, GRW ;
HASHIMOTO, SA ;
MORRISON, W ;
NELSON, J ;
GOODIN, DS ;
MASSA, SM ;
GUTTERIDGE, E ;
ARNASON, BGW ;
NORONHA, A ;
REDER, AT ;
MARTIA, R ;
EBERS, GC ;
RICE, GPA ;
LESAUX, J ;
JOHNSON, KP ;
PANITCH, HS ;
BEVER, CT ;
CONWAY, K ;
WALLENBERG, JC ;
BEDELL, L ;
VANDENNOORT, S ;
WEINSHENKER, B ;
WEISS, W ;
REINGOLD, S ;
PACHNER, A ;
TAYLOR, W .
NEUROLOGY, 1993, 43 (04) :655-661
[8]   Disability as an outcome in MS clinical trials [J].
Ebers, G. C. ;
Heigenhauser, L. ;
Daumer, M. ;
Lederer, C. ;
Noseworthy, J. H. .
NEUROLOGY, 2008, 71 (09) :624-631
[9]   Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis [J].
Ebers, GC ;
Rice, G ;
Lesaux, J ;
Paty, D ;
Oger, J ;
Li, DKB ;
Beall, S ;
Devonshire, V ;
Hashimoto, S ;
Hooge, J ;
Kastrukoff, L ;
Krieger, C ;
Mezei, M ;
Seland, P ;
Vorobeychi, G ;
Morrison, W ;
Nelson, J ;
Freedman, MS ;
Chrisie, S ;
Nelson, R ;
Rabinovitch, H ;
Freedman, C ;
Hartung, HP ;
Rieckmann, P ;
Archelos, J ;
Jung, S ;
Weilbach, F ;
Flachenecke, P ;
Sauer, J ;
Hommes, O ;
Jongen, P ;
Brouwer, S ;
McLeod, J ;
Pollard, J ;
Ng, R ;
Sandberg-Wollheim, M ;
Källén, K ;
Nilsson, P ;
Ekberg, R ;
Lundgren, A ;
Jadbäck, G ;
Wikström, J ;
Multanen, J ;
Valjakka, M ;
Carton, H ;
Lissoir, F ;
Declerq, I ;
Vieren, M ;
Peeters, E ;
Dubois, B .
LANCET, 1998, 352 (9139) :1498-1504
[10]   Predicting short-term disability in multiple sclerosis [J].
Gauthier, S. A. ;
Mandel, M. ;
Guttmann, C. R. G. ;
Glanz, B. I. ;
Khoury, S. J. ;
Betensky, R. A. ;
Weiner, H. L. .
NEUROLOGY, 2007, 68 (24) :2059-2065