Time to first relapse as an endpoint in multiple sclerosis clinical trials

Multiple Sclerosis Journal

Volumn 19, Issue 4, 2013, Pages 466-474

  Sormani, M P ^a   Signori, A ^a   Siri, P ^b   De Stefano, N ^c  

^a UNIVERSITY OF GENOA   (Italy)

^b POLITECNICO DI TORINO   (Italy)

^c UNIVERSITY OF SIENA   (Italy)

Author keywords

Annualized relapse rate; Clinical trial design; Clinical trial size; Multiple sclerosis; Primary outcome; Time to relapse

Indexed keywords

ARTICLE; CONTROLLED CLINICAL TRIAL (TOPIC); FEASIBILITY STUDY; HUMAN; MAJOR CLINICAL STUDY; MULTIPLE SCLEROSIS; OUTCOME ASSESSMENT; RECURRENCE RISK; RELAPSE; SAMPLE SIZE;

EID: 84877856766     PISSN: 13524585     EISSN: 14770970     Source Type: Journal    
DOI: 10.1177/1352458512457841     Document Type: Article

References (21)

1. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in Relapsing-Remitting Multiple Sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol 1993; 43: 655-661.
2. Johnson KP, Brooks BR, et al. Copolymer 1 reduces relapse rate and improves disability in Relapsing-Remitting Multiple Sclerosis: Results of a phase III multicenter, double-blind placebo-controlled trial. Neurol 1995; 45: 1268-1276.
3. Jacobs LD, Cookfair DL, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285-294. (Pubitemid 26100751)
4. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in Relapsing-Remitting Multiple Sclerosis. Lancet 1998; 352: 1498-1504.
5. Polman CH, O'Connor PW, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. NEJM 2006; 354: 899-910.
6. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. NEJM 2010; 362: 387-401.
7. Sormani MP, Li D, Bruzzi P, et al. Combined MRI lesions and relapses as a perfect surrogate for disability in multiple sclerosis. Neurol 2011; 77: 1684-1690.
8. Wang YC, Sandrock A, Richert JR et al Short-Term Relapse Quantitation as a Fully Surrogate Endpoint for Long-Term Sustained Progression of Disability in RRMS Patients Treated with Natalizumab- Neurology Research International, vol. 2011, Article ID 195831, 6 pages, 2011. doi:10.1155/2011/195831
9. Polman CH, Reingold SC, Barkhof F, et al. Ethics of placebo-controlled clinical trials in multiple sclerosis: A reassessment. Neurol 2008; 70: 1134-1140. (Pubitemid 351464771)
10. Inusah S, Sormani MP, Cofield SS, et al. Assessing changes in relapse rates in multiple sclerosis. Mult Scler 2010; 16: 1414-1421.
11. Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. NEJM 2000; 343: 898-904.
12. Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: A randomised study. Lancet 2001; 357: 1576-1582. (Pubitemid 32488815)
13. Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurol 2006; 67: 1242-1249. (Pubitemid 44563835)
14. Comi G, Martinelli V, Rodegher M et al. Effect of glatiramer acetate on conversion to clinically defi nite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374: 1503-11.
15. Comi G, De Stefano N, Freedman MS et al. Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial. Lancet Neurol 2012; 11: 33-41.
16. Wang YC, Meyerson L, Tang YQ, et al. Statistical methods for the analysis of relapse data in MS clinical trials. J Neurol Sci 2009; 285: 206-211.
17. Siri P, Henninger E and Sormani MP. A parametric model fitting time to first event for overdispersed data: Application to time to relapse in multiple sclerosis. Lifetime Data Anal 2012; 18: 139-156.
18. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. NEJM 2010; 362: 387-401.
19. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. NEJM 2010; 362: 416-426.
20. Nicholas R, Straube S, Schmidli H, et al. Time-patterns of annualized relapse rates in randomized placebo-controlled clinical trials in relapsing multiple sclerosis: A systematic review and meta-analysis. Mult Scler 2012; [Epub ahead of print].
21. Scalfari A, Neuhaus A, Degenhardt A, et al. The natural history of multiple sclerosis: A geographically based study 10: Relapses and long-term disability. Brain 2010; 133: 1914-1929.