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Multiple Sclerosis, Vol. 12, No. 6,
826-829 (2006)
DOI: 10.1177/1352458506070820
© 2006 SAGE Publications
Regression to the mean in multiple sclerosis
S Martínez-Yélamos
Multiple Sclerosis Unit, Service of Neurology, Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat, Barcelona 08907, Spain
A Martínez-Yélamos
Service of Neurology, Hospital de Viladecans, Viladecans, Barcelona 08840, Spain
G Martín Ozaeta
Multiple Sclerosis Unit, Service of Neurology, Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat, Barcelona 08907, Spain
V Casado
Multiple Sclerosis Unit, Service of Neurology, Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat, Barcelona 08907, Spain
O Carmona
Service of Neurology, Hospital de Figueres, Girona 17600, Spain
Tx Arbizu
Multiple Sclerosis Unit, Service of Neurology, Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat, Barcelona 08907, Spain, unitatem{at}scs.csub.es
In order to ensure sufficient disease activity, patients with relapsing remitting (RR) multiple sclerosis (MS) are often included in randomized placebo-controlled trials, only if they have a high baseline activity. These patients, whose evolution is unusual in the pre-study period, will tend to show a more usual behavior when followed up over a period of time. This phenomenon is known as regression to the mean. Regression to the mean should be taken into account in correctly interpreting long-term studies of cohorts treated without a placebo control group, which use the baseline period as control. The aim of this study was to evaluate the relevance of this phenomenon in a non-treated cohort of RRMS patients, selected with similar criteria to those used in randomized placebo-controlled clinical trials. Forty-four patients with definite RRMS, with two or more relapses in the previous two years, and a baseline EDSS  5.5 were prospectively followed. The mean number of relapses spontaneously decreased from 1.72 (SD: 1.4) in the year prior to enrolment, to 1.0 (SD: 1.3) during the first year of follow-up (PB < 0.05). Regression to the mean may explain as much as 40% of the reduction in the relapse rate from the baseline period to the period on-study.
Key Words: disability • glatiramer acetate • interferon beta • multiple sclerosis • randomized clinical trials • regression to the mean
References
- Filippini G, Munard L, Incovaia B, Ebers GC, Polman C, D’Amicoet al. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet 2003; 961: 545-552.
- Munai LM, Filippini G. Lack of evidence for use of glatiramer acetate in multiple sclerosis. Lancet Neurol 2004; 3: 641-641.[CrossRef][ISI][Medline]
[Order article via Infotrieve]
- Pryse-Phillips W. Twenty questions about multiple sclerosis clinical trials methodologies. Neurol Sci 2001; 22: 187-193.[CrossRef][ISI][Medline]
[Order article via Infotrieve]
- Wingerchuk DM, Noseworthy JH. Randomized controlled trials to assess therapies for multiple sclerosis. Neurology 2002; 58: S40-S48.[Abstract/Free Full Text]
- Weinshenker BG, Issa M, Baskerville J. Meta-analysis of the placebo-treated groups in clinical trials of progressive multiple sclerosis. Neurology 1996; 46: 1613-1619.[Abstract/Free Full Text]
- Goodin DS. Disease-modifying therapy in MS: a critical review of the literature. Part I: analysis of clinical trial errors. J Neurol 2004; 251: V/3-V/11.[Medline]
[Order article via Infotrieve]
- Waubant E, Vukusik S, Gignoux L, Dubief FD, Achiti I, Blanc Set al. Clinical characteristics of responders to interferon therapy for relapsing multiple sclerosis. Neurology 2003; 61: 184-189.[Abstract/Free Full Text]
- Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM and the Multiple Sclerosis Collaborative Research Group. Intramuscular inter-feron beta-1 for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285-294.[CrossRef][ISI][Medline]
[Order article via Infotrieve]
- The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 1995; 45: 1277-1285.[Abstract]
- Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP and the Copolymer 1 Multiple Sclerosis Study Group. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 1995; 45: 1268-1276.[Abstract]
- Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B, for the Austrian Immunoglobulin in Multiple Sclerosis Study Group. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet 1997; 349: 589-593.[CrossRef][ISI][Medline]
[Order article via Infotrieve]
- PRISMS (Prevention of Relapses and Disability by Interferon beta-1 a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1 a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498-1504.[CrossRef][ISI][Medline]
[Order article via Infotrieve]
- Noseworthy JH, O’Brien P, Erickson BJ, Lee D, Sneve D, Ebers GCet al. The Mayo Clinic-Canadian cooperative trial of sulfasalazine in active multiple sclerosis. Neurology 1998; 51: 1342-1352.[Abstract/Free Full Text]
- Confavreux C, Compston DAS, Hommes OR, McDonald WI, Thompson AJ. EDMUS, a European Database for Multiple Sclerosis. J Neurol Neurosurg Psychiatry 1992; 55: 671-676.[Abstract]
- Weinshenker BG, Rice GPA, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials. Brain 1991; 114: 1057-1067.[Abstract/Free Full Text]
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