Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
PLoS One. 2013 May 15;8(5):e62599. doi: 10.1371/journal.pone.0062599. Print 2013.
Placebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to 'active' treatments. A direct test for differences between placebo and 'active' treatment effects has not been conducted.
We aimed to test for differences between treatment and placebo effects within similar trial populations.
A Cochrane Review compared placebos with no treatment in three-armed trials (no treatment, placebo, and treatment). We added an analysis of treatment and placebo differences within the same trials. SYNTHESIS METHODS: For continuous outcomes we compared mean differences between placebo and no treatment with mean differences between treatment and placebo. For binary outcomes we compared the risk ratio for treatment benefit (versus placebo) with the risk ratio for placebo benefit (versus no treatment). We conducted several preplanned subgroup analyses: objective versus subjective outcomes, conditions tested in three or more trials, and trials with varying degrees of bias.
In trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = -0.29, 95% CI -0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).
Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.
尽管存在伦理限制，安慰剂在临床实践中仍被广泛应用。这种使用是否合理部分取决于安慰剂与“活性”治疗相比的相对益处。尚未进行安慰剂与“活性”治疗效果之间差异的直接测试。
我们旨在在类似的试验人群中测试治疗与安慰剂效果之间的差异。
Cochrane 综述比较了三臂试验中安慰剂与无治疗（无治疗、安慰剂和治疗）的效果。我们在同一试验中增加了治疗和安慰剂差异的分析。
对于连续结果，我们比较了安慰剂与无治疗之间的平均差异与治疗与安慰剂之间的平均差异。对于二分类结果，我们比较了治疗获益（与安慰剂相比）的风险比与安慰剂获益（与无治疗相比）的风险比。我们进行了几项预先计划的亚组分析：客观与主观结果、在三项或更多试验中测试的条件，以及具有不同程度偏倚的试验。
对于连续结果的试验（n=115），我们未发现治疗与安慰剂效果之间存在差异（MD=-0.29，95%CI-0.62 至 0.05，P=0.10）。对于二分类结果的试验（n=37），治疗明显优于安慰剂（RRR=0.72，95%CI=0.61 至 0.86，P=0.0003）。在 28 项预先定义的亚组分析中的 22 项中，治疗与安慰剂效果无差异。在六个存在差异的亚组中，有五个治疗优于安慰剂。然而，当排除所有减少偏倚的标准（连续结果）时，安慰剂的效果优于治疗（MD=1.59，95%CI=0.40 至 2.77，P=0.009）。
安慰剂和治疗通常具有相似的效果大小。具有相对强大效果的安慰剂可以单独或作为治疗方案的一部分使患者受益，并且必须对涉及此类安慰剂的试验进行充分的盲法。
