The importance of allocation concealment and patient blinding in osteoarthritis trials: a meta-epidemiologic study.
OBJECTIVE
To evaluate the association of adequate allocation concealment and patient blinding with estimates of treatment benefits in osteoarthritis trials.


METHODS
We performed a meta-epidemiologic study of 16 meta-analyses with 175 trials that compared therapeutic interventions with placebo or nonintervention control in patients with hip or knee osteoarthritis. We calculated effect sizes from the differences in means of pain intensity between groups at the end of followup divided by the pooled SD and compared effect sizes between trials with and trials without adequate methodology.


RESULTS
Effect sizes tended to be less beneficial in 46 trials with adequate allocation concealment compared with 112 trials with inadequate or unclear concealment of allocation (difference -0.15; 95% confidence interval [95% CI] -0.31, 0.02). Selection bias associated with inadequate or unclear concealment of allocation was most pronounced in meta-analyses with large estimated treatment benefits (P for interaction < 0.001), meta-analyses with high between-trial heterogeneity (P = 0.009), and meta-analyses of complementary medicine (P = 0.019). Effect sizes tended to be less beneficial in 64 trials with adequate blinding of patients compared with 58 trials without (difference -0.15; 95% CI -0.39, 0.09), but differences were less consistent and disappeared after accounting for allocation concealment. Detection bias associated with a lack of adequate patient blinding was most pronounced for nonpharmacologic interventions (P for interaction < 0.001).


CONCLUSIONS
Results of osteoarthritis trials may be affected by selection and detection bias. Adequate concealment of allocation and attempts to blind patients will minimize these biases.
Nüesch
Eveline
E
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Reichenbach
Stephan
S
Trelle
Sven
S
Rutjes
Anne W S
AW
Liewald
Katharina
K
Sterchi
Rebekka
R
Altman
Douglas G
DG
Jüni
Peter
P
D015982:Bias; D002986:Clinical Trials as Topic; D000529:Complementary Therapies; D003625:Data Collection / Q000379:methods*; D016021:Epidemiologic Studies; D006801:Humans; D015207:Osteoarthritis, Hip / Q000503:physiopathology / Q000628:therapy*; D020370:Osteoarthritis, Knee / Q000503:physiopathology / Q000628:therapy*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D016037:Single-Blind Method; D016896:Treatment Outcome