Intervention Review

Placebo interventions for all clinical conditions

  1. Asbjørn Hróbjartsson*,
  2. Peter C Gøtzsche

Editorial Group: Cochrane Consumers and Communication Group

Published Online: 20 JAN 2010

Assessed as up-to-date: 10 NOV 2009

DOI: 10.1002/14651858.CD003974.pub3

Database Title

Additional Information

How to Cite

Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD003974. DOI: 10.1002/14651858.CD003974.pub3.

Author Information

  1. Rigshospitalet, The Nordic Cochrane Centre, Copenhagen, Denmark

*Asbjørn Hróbjartsson, The Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, 3343, Copenhagen, 2100, Denmark. ah@cochrane.dk.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 20 JAN 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published.

Objectives

Our primary aims were to assess the effect of placebo interventions in general across all clinical conditions, and to investigate the effects of placebo interventions on specific clinical conditions. Our secondary aims were to assess whether the effect of placebo treatments differed for patient-reported and observer-reported outcomes, and to explore other reasons for variations in effect.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 4, 2007), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), PsycINFO (1887 to March 2008) and Biological Abstracts (1986 to March 2008). We contacted experts on placebo research, and read references in the included trials.

Selection criteria

We included randomised placebo trials with a no-treatment control group investigating any health problem.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Trials with binary data were summarised using relative risk (a value of less than 1 indicates a beneficial effect of placebo), and trials with continuous outcomes were summarised using standardised mean difference (a negative value indicates a beneficial effect of placebo).

Main results

Outcome data were available in 202 out of 234 included trials, investigating 60 clinical conditions. We regarded the risk of bias as low in only 16 trials (8%), five of which had binary outcomes.

In 44 studies with binary outcomes (6041 patients), there was moderate heterogeneity (P < 0.001; I2 45%) but no clear difference in effects between small and large trials (symmetrical funnel plot). The overall pooled effect of placebo was a relative risk of 0.93 (95% confidence interval (CI) 0.88 to 0.99). The pooled relative risk for patient-reported outcomes was 0.93 (95% CI 0.86 to 1.00) and for observer-reported outcomes 0.93 (95% CI 0.85 to 1.02). We found no statistically significant effect of placebo interventions in four clinical conditions that had been investigated in three trials or more: pain, nausea, smoking, and depression, but confidence intervals were wide. The effect on pain varied considerably, even among trials with low risk of bias.

In 158 trials with continuous outcomes (10,525 patients), there was moderate heterogeneity (P < 0.001; I2 42%), and considerable variation in effects between small and large trials (asymmetrical funnel plot). It is therefore a questionable procedure to pool all the trials, and we did so mainly as a basis for exploring causes for heterogeneity. We found an overall effect of placebo treatments, standardised mean difference (SMD) -0.23 (95% CI -0.28 to -0.17). The SMD for patient-reported outcomes was -0.26 (95% CI -0.32 to -0.19), and for observer-reported outcomes, SMD -0.13 (95% CI -0.24 to -0.02). We found an effect on pain, SMD -0.28 (95% CI -0.36 to -0.19)); nausea, SMD -0.25 (-0.46 to -0.04)), asthma (-0.35 (-0.70 to -0.01)), and phobia (SMD -0.63 (95% CI -1.17 to -0.08)). The effect on pain was very variable, also among trials with low risk of bias. Four similarly-designed acupuncture trials conducted by an overlapping group of authors reported large effects (SMD -0.68 (-0.85 to -0.50)) whereas three other pain trials reported low or no effect (SMD -0.13 (-0.28 to 0.03)). The pooled effect on nausea was small, but consistent. The effects on phobia and asthma were very uncertain due to high risk of bias. There was no statistically significant effect of placebo interventions in the seven other clinical conditions investigated in three trials or more: smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, but confidence intervals were wide.

Meta-regression analyses showed that larger effects of placebo interventions were associated with physical placebo interventions (e.g. sham acupuncture), patient-involved outcomes (patient-reported outcomes and observer-reported outcomes involving patient cooperation), small trials, and trials with the explicit purpose of studying placebo. Larger effects of placebo were also found in trials that did not inform patients about the possible placebo intervention.

Authors' conclusions

We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Placebo interventions for all clinical conditions

Placebo interventions are often claimed to substantially improve many clinical conditions. However, most reports on effects of placebos are based on unreliable studies that have not randomised patients to placebo or no treatment.

We studied the effect of placebo treatments by reviewing 202 trials comparing placebo treatment with no treatment covering 60 healthcare problems. In general, placebo treatments produced no major health benefits, although on average they had a modest effect on outcomes reported by patients, such as pain. However, the effect on pain varied from large to non-existent, even in well-conducted trials. Variations in the effect of placebo was partly explained by variations in how trials were conducted, the type of placebo used, and whether patients were informed that the trial involved placebo.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以安慰劑介入於所有臨床狀況

安慰劑 (placebo) 的使用經常被認為可以改善病患報告結果(patientreported outcomes)以及觀察者報告結果(observerreported outcomes)，但這種信念並非依據比較使用安慰劑與不使用任何治療的隨機臨床試驗而來。

目標

我們的主要目標為評估安慰劑介入對整體及特殊臨床狀況的效果，次要目標為評估安慰劑治療對於病患陳述或觀察者陳述結果之間的效果差異並探詢產生效果變異的其他原因。

搜尋策略

我們搜索了Cochrane Central Register of Controlled Trials (CENTRAL) 資料庫(2002年Cochrane Library第4期)，1966年至2002年間MEDLINE資料庫，1980年至2002年間EMBASE資料庫，1986年至2002年Biological摘要，以及1887年至2002年的PsycLIT資料庫。我們聯繫研究安慰劑方面的專家，並參考所納入臨床試驗的相關文獻。

選擇標準

我們納入任何觀察健康問題合併未有任何治療的對照組之隨機安慰劑臨床試驗。

資料收集與分析

由兩位評論作者獨立進行臨床試驗特性及資料摘錄的評估。我們同時也為了取得額外的資訊而聯絡了研究作者。

主要結論

研究數據結果是從182個可利用的臨床試驗中，選出其中的156個，來研究46種臨床狀況。我們在38個以二元結果(binary outcomes)呈現的研究中(總共有4284位病人)，並沒有在統計上發現安慰劑整體的影響，相對危險性(relative risk 0.95 (95% confidence interval (CI) 95% 信賴區間0.89 到 1.01))。病患報告結果的整體的相對危險性(relative risk) 為0.95 (95% 信賴區間0.88 到 1.03) ，觀察者報告結果的相對危險性relative risk為0.91 (95% 信賴區間0.81 1.03) 。雖然出現異質性(heterogeneity)(P = 0.01)，但漏斗散佈圖是對稱的。雖然信賴區間是寬鬆的，但我們在3個臨床試驗中，一共調查研究了4種臨床症狀(疼痛、噁心、抽煙以及憂鬱)，發現在統計學上，安慰劑的介入並沒有任何顯著的意義。我們從118個持續追蹤的臨床試驗結果中(7453位病人)，發現了安慰劑治療的整體效果，標準化平均差 (SMD) 為 −0.24 (95% 信賴區間CI −0.31 to −0.17) 。在病患報告結果中的標準化平均差為 −0.30 (95% 信賴區間CI −0.38 to −0.21) ，在觀察者報告結果中SMD標準化平均差為 −0.10 (95% 信賴區間CI −0.20 to −0.01) ，不具統計學上顯著的意義。縱使在大型的臨床試驗中，仍出現異質性(heterogeneity)(P<0.001)以及出現變異性很大的漏斗散佈圖。安慰劑的介入在疼痛 (SMD −0.25 (95% CI −0.35 to −0.16)) 以及在恐懼症 (SMD −0.63 (95% CI −1.17 to −0.08)) 有明顯的影響，但仍有潛在的偏差風險(risk of bias)。安慰劑的介入在超過3個臨床試驗中發現，對於8個其他的臨床症狀(噁心、抽煙、憂鬱、體重過重、氣喘、高血壓、失眠以及焦慮)來說，雖然信賴區間(confidence intervals)較寬，但在統計學上並沒有顯著的影響。

作者結論

整體上沒有證據顯示，服用安慰劑有顯著的臨床影響。在持續的病者報告結果中，特別是對疼痛的病人來說，安慰劑可能有些微影響，但無法明確與偏差區分。

翻譯人

本摘要由成功大學附設醫院蔡佩蓉翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

尚無任何證據顯示安慰劑的治療方式具有顯著的效果，雖然在針對疼痛的病人報告結果中，可能有些微的影響。普遍相信安慰劑(不具療效的藥；虛擬變數，例如：糖片劑)的治療方式，在差異性大的健康問題上，有其重要的影響。但這個理論並不是依據比對使用安慰劑治療，以及不使用任何治療的隨機臨床試驗而來的。我們重新探討了在不同形式的健康照護問題上，超過150個研究安慰劑治療效果的臨床試驗，發現安慰劑的治療方式對健康並沒有助益，但是對疼痛的病人來說，可能有些微的影響。

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