Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors.
BACKGROUND
Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales.


METHODS
We conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more optimistic estimates of effect. We pooled the differences in effect size using inverse variance random-effects meta-analysis and used metaregression to identify potential reasons for variation.


RESULTS
We included 24 trials in our review. The main meta-analysis included 16 trials (involving 2854 patients) with subjective outcomes. The estimated treatment effect was more beneficial when based on nonblinded assessors (pooled difference in effect size -0.23 [95% confidence interval (CI) -0.40 to -0.06]). In relative terms, nonblinded assessors exaggerated the pooled effect size by 68% (95% CI 14% to 230%). Heterogeneity was moderate (I(2) = 46%, p = 0.02) and unexplained by metaregression.


CONCLUSIONS
We provide empirical evidence for observer bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk of substantial bias.
Nordic Cochrane Centre, Rigshospitalet Department 7811, Copenhagen, Denmark. ah@cochrane.dk
Asbjørn
A
Hróbjartsson
Ann Sofia Skou
AS
Thomsen
Frida
F
Emanuelsson
Britta
B
Tendal
Jørgen
J
Hilden
Isabelle
I
Boutron
Philippe
P
Ravaud
Stig
S
Brorson
D004311:Double-Blind Method; D015588:Observer Variation; D017063:Outcome Assessment, Health Care / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*