Predictors for relapses – Association of variables with outcomes within a mixed-effect model.

<p>Taû2 is the estimate of residual heterogeneity. A higher reduction of taû2 within the mixed-effect models indicate a higher association with outcome. Testing for residual heterogeneity was significant with p<0.0001 in all cases. RRF  =  Rate of relapse free patients after 2 years, ARR  =  Annualized relapse rate over 2 years, CI  =  Confidence interval.</p

Flow chart: Study selection for meta-analyses.

<p>According to the PRISMA guidelines. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050347#pone.0050347-Moher1" target="_blank">[15]</a>.</p

Change of mean age and pre-study relapse rates of MS phase-3 placebo cohorts over time.

<p>N = 13. Circle size corresponds to weighting by patient numbers of each cohort. R2 is the proportion of variability in the data that is accounted for by the weighted univariate regression model.</p

Overview of included RRMS phase-3 trials (n = 13).

<p>RRF  =  Rate of relapse free patients after 2 years, SE  =  Standard error, ARR  =  Annualized relapse rate over 2 years, SD  =  Standard deviation, 2001/2005 indicates the use of the original 2001 McDonald criteria or the 2005 revised criteria.</p

Descriptive statistics of the individual patient cohort (SLC database).

<p>SD  =  Standard deviation.</p

Predictors for relapses - coefficient of determination in weighted regression models.

<p>Coefficient estimates and coefficient of determination (adjusted R2) of univariate regression models of baseline variables and outcomes. R2 is the proportion of variability in the data that is accounted for by univariate regression model. Variables were also analysed for their change over time (variables vs. start date). Significant (p<0.05 (*)) correlations were used for the multivariate modelling. RRF  =  Rate of relapse free patients after 2 years, ARR  =  Annualized relapse rate over 2 years.</p

Change of annualized relapse rates of MS phase-3 placebo cohorts over time.

<p>n = 13. Circle size corresponds to weighting by patient numbers of each cohort. R2 is the proportion of variability in the data that is accounted for by the weighted univariate regression model.</p

Individual patient cohort – final Poisson and logistic regression models.

<p>ARR  =  Annualized relapse rate over 2 years, Logistic regression: Outcome was coded as 1 for at least 1 relapse in 2 years or 0 for no relapse in 2 years, reference category for trial entry was 1990 or earlier.</p

Results of the multiple logistic regressions after automatic selection, approach 1, early detectable parameters and approach 2, later detectable parameters.

<p>Results of the multiple logistic regressions after automatic selection, approach 1, early detectable parameters and approach 2, later detectable parameters.</p

CONSORT flow diagram of the WestGem-study.

<p>CONSORT flow diagram of the WestGem-study.</p