The importance of allocation concealment and patient blinding in osteoarthritis trials: a meta-epidemiologic study

OBJECTIVE: To evaluate the association of adequate allocation concealment andpatient blinding with estimates of treatment benefits in osteoarthritis trials.METHODS: We performed a meta-epidemiologic study of 16 meta-analyses with 175trials that compared therapeutic interventions with placebo or noninterventioncontrol in patients with hip or knee osteoarthritis. We calculated effect sizesfrom the differences in means of pain intensity between groups at the end offollowup divided by the pooled SD and compared effect sizes between trials withand trials without adequate methodology.RESULTS: Effect sizes tended to be less beneficial in 46 trials with adequateallocation concealment compared with 112 trials with inadequate or unclearconcealment of allocation (difference -0.15; 95% confidence interval [95% CI]-0.31, 0.02). Selection bias associated with inadequate or unclear concealment ofallocation was most pronounced in meta-analyses with large estimated treatmentbenefits (P for interaction < 0.001), meta-analyses with high between-trialheterogeneity (P = 0.009), and meta-analyses of complementary medicine (P =0.019). Effect sizes tended to be less beneficial in 64 trials with adequateblinding of patients compared with 58 trials without (difference -0.15; 95% CI-0.39, 0.09), but differences were less consistent and disappeared afteraccounting for allocation concealment. Detection bias associated with a lack ofadequate patient blinding was most pronounced for nonpharmacologic interventions (P for interaction < 0.001).CONCLUSION: Results of osteoarthritis trials may be affected by selection anddetection bias. Adequate concealment of allocation and attempts to blind patientswill minimize these biases.