This manuscript describes the outline of a double-blind, placebo-controlled, (European), multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-1b given subcutaneously every other day for 3 years in patients with secondary progressive multiple sderosis. The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Expanded Disability Status Scale. The essentials of the study design are presented, induding the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters.
The IFNB Multiple Sclerosis Study Group. (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology43: 655-661.
2.
PatyDW
. (1993) Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis result of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology43: 662-667.
3.
EbersGC. (1994) Treatment of multiple sclerosis. Lancet343: 275-279.
4.
KurtzkeJF. (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology33: 1444-1452.
5.
WeinshenkerBG
. (1991) The natural history of multiple sclerosis: a geographically based study. IV: applications to planning and interpretation of clinical therapeutic trials. Brain114: 1057-1067.
6.
McDonaldWI, MillerDH, ThompsonAJ. (1994) Are magnetic resonance findings predictive of clinical out-come in therapeutic trials in multiple sclerosis? The dilemma of Interferon-beta. Ann Neurol36: 14-18.
7.
KurtzkeJF. (1955) A new scale for evaluating disability in multiple sclerosis. Neurology5: 580-583.
8.
NoseworthyJH
. (1990) Interrater variability with the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial. Neurology40: 971-975.
9.
WilloughbyEW, PatyDW. (1988) Scales for rating impairment in multiple sclerosis: a critique. Neurology38: 1793-1798.
10.
WeinshenkerBG, BaskervilleJ, EbersCG. (1993) Identifying suitable candidates for clinical trials of progressive MS. In: 9th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Final Program Abstracts. Florence October 31-November 2, 1993: 47.
HauserSL
. (1983) Intensive immunosuppression in progressive multiple sclerosis. N Engl J Med308: 173-180.
13.
Workshop on Outcomes Assessment in Multiple Sclerosis Clinical Trials. (1994) A Critical Analysis, February23-27. Charleston, South Carolina, USA.
14.
FilippiM
. (1994) Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis. Neurology44: 635-641.
15.
GassA
. (1994) Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis. Ann Neurol36: 62-67.
16.
KoopmansRA,
. (1989) Benign versus chronic progressive multiple sclerosis: magnetic resonance imaging features. Ann Neurol25: 74-81.
17.
MillerDH, BarkhofF, NautaJJP. (1993) Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. Brain116: 1077-1094.
18.
Van WalderveenMAA,
. (1994) Correlation of quantitative MRI abnormalities and disability in MS. J Neurol241 (suppl. 1): 38.
19.
BarkhofF
. (1992) Relapsing remitting multiple sclerosis: Sequential enhanced MR imaging vs clinical findings in determining disease activity. Am J Reortgenol159: 1041-1047.
20.
IsaacC
. (1988) Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology38: 1511-1515.
21.
KoopmansRA
. (1989) Chronic progressive multiple sclerosis: serial magnetic resonance brain imaging over six months. Ann Neurol26: 248-256.
22.
ThompsonAJ
. (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol29: 53-62.
23.
ThompsonAJ
. (1990) Patterns of disease activity in multiple sclerosis: a clinical and magnetic resonance imaging study. Br Med J300: 631-634.
24.
ThompsonAJ
. (1992) Serial gadolinium enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. Neurology42: 60-63.
25.
NautaJJP, ThompsonAJ, BarkhofF, MillerDH. (1994) Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: statistical power of parallel groups and crossover designs. J Neurol Sci122: 6-14.
26.
McDonaldWI. (1994) Rachelle Fishman-Matthew Moore Lecture: the pathological and clinical dynamics of multiple sclerosis. J. Neuropathol Exp Neurol53: 338-343.
