Explaining temporal trends in annualized relapse rates in placebo groups of randomized controlled trials in relapsing multiple sclerosis
de
dc.title.alternative
Systematic review, meta-analysis and meta-regression
de
dc.type
doctoralThesis
de
dc.contributor.referee
Friede, Tim Prof. Dr.
dc.date.examination
2014-01-21
dc.description.abstracteng
Recent studies have shown a decrease in annualized relapse rates (ARRs) in placebo groups of
randomized controlled trials (RCTs) in relapsing multiple sclerosis (RMS). This dissertation
aimed to describe this trend in a different set of RCTs and to investigate whether patient baseline
characteristics, eligibility criteria and other study design features could explain this
phenomenon.
A literature search of randomized, placebo-controlled trials in RMS offering data on relapses
in placebo groups identified 56 suitable trials. Data on eligibility criteria and baseline
characteristics were extracted and tested for significant trends over time.
Several temporal trends were identified: The number of years considered for the calculation of
pre-trial ARR as well as pre-trial ARRs themselves decreased, as did the duration of placebocontrolled follow-up. Pre-trial ARRs of the first and second preceding year before baseline
showed major inconsistencies. Limits of eligible age as well as mean age increased, as did the
mean disease duration, the number of eligibility criteria and the number of words and characters
describing them, scores on the OQS, the number of treatment arms and the average number of
patients per treatment arm.
A meta-regression was conducted to estimate the contribution of these temporal trends to the
decrease of trial ARRs over time. In the final meta-regression modeling of the trial placebo
ARR, the date of publication was found to be insignificant in explaining the variation in trial
placebo ARR, whereas pre-trial ARR, the number of years used to calculate pre-trial ARR,
disease duration and the duration of follow-up became major contributors.
In conclusion, the decline in trial ARRs most likely results from decreasing pre-trial ARRs and
a shorter time period over which these were calculated. Increasing duration of illness may also
contribute to the phenomenon.
de
dc.contributor.coReferee
Simons, Mikael Prof. Dr.
dc.contributor.thirdReferee
Oppermann, Martin Prof. Dr.
dc.subject.eng
multiple sclerosis
de
dc.subject.eng
relapsing
de
dc.subject.eng
placebo groups
de
dc.subject.eng
temporal trends
de
dc.subject.eng
systematic review
de
dc.subject.eng
meta-analysis
de
dc.subject.eng
meta-regression
de
dc.identifier.urn
urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5DFE-E-8
dc.affiliation.institute
Medizinische Fakultät
de
dc.subject.gokfull
Medizin (PPN619874732)
de
dc.subject.gokfull
Medizinische Statistik / Biometrie / Epidemiologie - Allgemein- und Gesamtdarstellungen (PPN619875046)