Hróbjartsson A, Gøtzsche P C
Department of Medical Philosophy and Clinical Theory, University of Copenhagen, Panum Institute, and the Nordic Cochrane Centre, Rigshospitalet, Denmark.
N Engl J Med. 2001 May 24;344(21):1594-602. doi: 10.1056/NEJM200105243442106.
Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated.
We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation).
We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes (pooled relative risk of an unwanted outcome with placebo, 0.95; 95 percent confidence interval, 0.88 to 1.02), regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect (pooled standardized mean difference in the value for an unwanted outcome between the placebo and untreated groups, -0.28; 95 percent confidence interval, -0.38 to -0.19), but the effect decreased with increasing sample size, indicating a possible bias related to the effects of small trials. The pooled standardized mean difference was significant for the trials with subjective outcomes (-0.36; 95 percent confidence interval, -0.47 to -0.25) but not for those with objective outcomes. In 27 trials involving the treatment of pain, placebo had a beneficial effect (-0.27; 95 percent confidence interval, -0.40 to -0.15). This corresponded to a reduction in the intensity of pain of 6.5 mm on a 100-mm visual-analogue scale.
We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.
据报道，安慰剂治疗有助于许多疾病的患者，但支持这一发现的证据质量尚未得到严格评估。
我们对临床试验进行了系统评价，其中患者被随机分配接受安慰剂或不治疗。安慰剂可以是药理的（例如片剂）、物理的（例如手法操作）或心理的（例如谈话）。
我们确定了130项符合纳入标准的试验。在排除16项没有相关结局数据的试验后，有32项试验有二元结局（涉及3795名患者，每项试验中位数为51名患者），82项试验有连续结局（涉及4730名患者，每项试验中位数为27名患者）。与不治疗相比，安慰剂对二元结局没有显著影响（安慰剂导致不良结局的合并相对风险为0.95；95%置信区间为0.88至1.02），无论这些结局是主观的还是客观的。对于有连续结局的试验，安慰剂有有益作用（安慰剂组与未治疗组不良结局值的合并标准化均值差为-0.28；95%置信区间为-0.38至-0.19），但该作用随着样本量增加而减小，表明可能存在与小试验效应相关的偏差。对于主观结局的试验，合并标准化均值差显著（-0.36；95%置信区间为-0.47至-0.25），而对于客观结局的试验则不显著。在27项涉及疼痛治疗的试验中，安慰剂有有益作用（-0.27；95%置信区间为-0.40至-0.15）。这相当于在100毫米视觉模拟量表上疼痛强度降低了6.5毫米。
总体而言，我们几乎没有发现安慰剂有强大临床效果的证据。虽然安慰剂对客观或二元结局没有显著影响，但在有连续主观结局的研究以及疼痛治疗方面可能有小的益处。在临床试验之外，没有理由使用安慰剂。
