title: A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients. Multiple Sclerosis Collaborative Research Group (MSCRG).
abstract: The design and conduct of a randomized, double-blinded, placebo-controlled, multicenter, phase III study of recombinant interferon beta-1a (IFN-beta-1a) as treatment for exacerbating-remitting MS are described, as are baseline characteristics of the study population. The purpose of the study was to determine if 6.0 x 10(6) IU (30 micrograms) of IFN-beta-1a, administered by weekly intramuscular (i.m.) injections, was effective in delaying the onset of sustained disability. The primary outcome measure was time to onset of treatment failure, defined as a worsening on the Kurtzke Expanded Disability Status Scale (EDSS) of greater than or equal to 1.0 point compared with baseline, persisting for at least 6 months. An intent-to-treat design was used. The primary outcome measure was analyzed using the Mantel-Cox log-rank statistic and Kaplan-Meier survival curves. Secondary outcomes included quantitative measures of upper and lower extremity function, neuropsychological test performance, functional and quality of life assessments and several measures derived from annual brain MRI studies. Entry criteria included prestudy exacerbation rates of at least 0.67 per year and EDSS scores of 1.0-3.5. A total of 301 MS patients were randomly assigned to receive weekly i.m. injections of IFN-beta-1a or placebo. The average age of the study population at entry was 37 years; 92% were Caucasian and 73% were women. The mean prestudy disease duration was 6.5 years, mean prestudy exacerbation rate was 1.2 per year and the mean EDSS score was 2.3. The randomization yielded well-balanced treatment arms. Various aspects of the study are discussed, including: (1) the decision to focus study design on sustained disability; (2) the rationale for the treatment regimen; (3) measures taken to assure the reliability of the primary outcome measure; and (4) a description of the secondary outcome measures.
authors.affiliation: William C. Baird Multiple Sclerosis Research Center, Millard Fillmore Health System, Buffalo, NY 14209, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Jacobs
authors.forename: D L
authors.initials: DL
authors.lastname: Cookfair
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: R M
authors.initials: RM
authors.lastname: Herndon
authors.forename: J R
authors.initials: JR
authors.lastname: Richert
authors.forename: A M
authors.initials: AM
authors.lastname: Salazar
authors.forename: J S
authors.initials: JS
authors.lastname: Fischer
authors.forename: D E
authors.initials: DE
authors.lastname: Goodkin
authors.forename: C V
authors.initials: CV
authors.lastname: Granger
authors.forename: J H
authors.initials: JH
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols / Q000592:standards; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D018579:Patient Selection; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D011994:Recombinant Proteins; D016899:Interferon-beta