Nüesch Eveline, Reichenbach Stephan, Trelle Sven, Rutjes Anne W S, Liewald Katharina, Sterchi Rebekka, Altman Douglas G, Jüni Peter
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Arthritis Rheum. 2009 Dec 15;61(12):1633-41. doi: 10.1002/art.24894.
To evaluate the association of adequate allocation concealment and patient blinding with estimates of treatment benefits in osteoarthritis trials.
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.
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).
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.
评估在骨关节炎试验中，充分的分配隐藏和患者设盲与治疗获益估计值之间的关联。
我们对16项荟萃分析进行了一项元流行病学研究，这些荟萃分析涵盖了175项试验，这些试验比较了髋或膝骨关节炎患者的治疗性干预措施与安慰剂或无干预对照。我们通过随访结束时组间疼痛强度均值的差异除以合并标准差来计算效应量，并比较了方法充分和方法不充分的试验之间的效应量。
与112项分配隐藏不充分或不明确的试验相比，46项分配隐藏充分的试验的效应量往往益处较小（差异为-0.15；95%置信区间[-0.31, 0.02]）。在估计治疗获益大的荟萃分析（交互作用P<0.001）、试验间异质性高的荟萃分析（P = 0.）和补充医学的荟萃分析（P = 0.019）中，与分配隐藏不充分或不明确相关的选择偏倚最为明显。与58项未充分设盲患者的试验相比，64项充分设盲患者的试验的效应量往往益处较小（差异为-0.15；95%置信区间[-0.39, 0.09]），但差异不太一致，在考虑分配隐藏后消失。与缺乏充分患者设盲相关的检测偏倚在非药物干预中最为明显（交互作用P<0.001）。
骨关节炎试验的结果可能受到选择和检测偏倚的影响。充分的分配隐藏和使患者设盲的努力将使这些偏倚最小化。
