Spontaneous improvement in randomised clinical trials: meta-analysis of three-armed trials comparing no treatment, placebo and active intervention
Spontaneous improvement in randomised clinical trials: meta-analysis of three-armed trials comparing no treatment, placebo and active intervention
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DOI：
10.1186/1471-2288-9-1
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发表时间：
2009-01-05
影响因子：
4
通讯作者：
Gotzsche, Peter C.
中科院分区：
文献类型：
--
作者：
Krogsboll, Lasse Theis;Hrobjartsson, Asbjorn;Gotzsche, Peter C.
背景：对于患者和临床医生来说，在给予治疗后正确解释临床状况的变化是具有挑战性的。目前尚不清楚自发改善、安慰剂的作用和积极干预的作用在多大程度上促成了观察到的基线变化，我们的目标是量化这些贡献。方法：系统回顾和荟萃分析，基于Cochrane回顾安慰剂干预对所有临床条件的影响。我们选择了所有将患者随机分为三组的试验：无治疗组、安慰剂组和积极干预组，并且采用连续量表或分级量表测量结果。在少于三个试验中被研究的临床状况被排除在外。结果：我们分析了37项试验（2900例患者），涵盖了8种临床情况。17项试验采用心理干预，15项试验采用物理干预，5项试验采用药物干预。总的来说，在所有条件和干预措施中，三个组的基线数据都有统计学上的显著变化。未治疗组与基线变化的标准化平均差（SMD）为0.24(95%可信区间-0.36至-0.12)，安慰剂组为-0.44(-0.61至-0.28)，积极治疗组为-1.01（-1.16至-0.86）。因此，平均而言，自发改善和安慰剂对主动干预的相对贡献分别为24%和20%，但如三种smd的置信区间所示，存在一些不确定性。自发改善最明显的情况是恶心（45%）、吸烟（40%）、抑郁（35%）、恐惧（34%）和急性疼痛（25%）。结论：在积极治疗的患者中，安慰剂的自发改善和疗效对观察到的治疗效果有重要贡献，但这些因素的相对重要性因临床情况和干预而异。
Background: It can be challenging for patients and clinicians to properly interpret a change in the clinical condition after a treatment has been given. It is not known to which extent spontaneous improvement, effect of placebo and effect of active interventions contribute to the observed change from baseline, and we aimed at quantifying these contributions.Methods: Systematic review and meta-analysis, based on a Cochrane review of the effect of placebo interventions for all clinical conditions. We selected all trials that had randomised the patients to three arms: no treatment, placebo and active intervention, and that had used an outcome that was measured on a continuous scale or on a ranking scale. Clinical conditions that had been studied in less than three trials were excluded.Results: We analysed 37 trials (2900 patients) that covered 8 clinical conditions. The active interventions were psychological in 17 trials, physical in 15 trials, and pharmacological in 5 trials. Overall, across all conditions and interventions, there was a statistically significant change from baseline in all three arms. The standardized mean difference (SMD) for change from baseline was 0.24 (95% confidence interval -0.36 to -0.12) for no treatment, -0.44 (-0.61 to -0.28) for placebo, and -1.01 (-1.16 to -0.86) for active treatment. Thus, on average, the relative contributions of spontaneous improvement and of placebo to that of the active interventions were 24% and 20%, respectively, but with some uncertainty, as indicated by the confidence intervals for the three SMDs. The conditions that had the most pronounced spontaneous improvement were nausea (45%), smoking (40%), depression (35%), phobia (34%) and acute pain (25%).Conclusion: Spontaneous improvement and effect of placebo contributed importantly to the observed treatment effect in actively treated patients, but the relative importance of these factors differed according to clinical condition and intervention.