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Meta-Analysis
. 2010 Jan 20;2010(1):CD003974.
doi: 10.1002/14651858.CD003974.pub3.

Placebo interventions for all clinical conditions

Asbjørn Hróbjartsson  1 , Peter C Gøtzsche
Affiliations
Meta-Analysis

Placebo interventions for all clinical conditions

Asbjørn Hróbjartsson et al. Cochrane Database Syst Rev. .

Abstract

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 strategy: 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; I(2) 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; I(2) 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.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgments about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgments about each methodological quality item presented as percentages across all included studies.
3
3
Funnel plot of comparison: 1 Main analysis: overall pooled analyses, outcome: 1.1 Binary outcomes.
4
4
Funnel plot of comparison: 1 Main analysis: overall pooled analyses, outcome: 1.2 Continuous outcomes.
1.1
1.1. Analysis
Comparison 1 Main analysis: overall pooled analyses, Outcome 1 Binary outcomes.
1.2
1.2. Analysis
Comparison 1 Main analysis: overall pooled analyses, Outcome 2 Continuous outcomes.
2.1
2.1. Analysis
Comparison 2 Main analysis: patient‐reported or observer‐reported outcomes, Outcome 1 Patient‐reported binary outcomes.
2.2
2.2. Analysis
Comparison 2 Main analysis: patient‐reported or observer‐reported outcomes, Outcome 2 Observer‐reported binary outcomes.
2.3
2.3. Analysis
Comparison 2 Main analysis: patient‐reported or observer‐reported outcomes, Outcome 3 Patient‐reported continuous outcomes.
2.4
2.4. Analysis
Comparison 2 Main analysis: patient‐reported or observer‐reported outcomes, Outcome 4 Observer‐reported continuous outcomes.
3.1
3.1. Analysis
Comparison 3 Main analysis: clinical conditions investigated in three trials or more, Outcome 1 Binary outcomes.
3.2
3.2. Analysis
Comparison 3 Main analysis: clinical conditions investigated in three trials or more, Outcome 2 Continuous outcomes.
4.1
4.1. Analysis
Comparison 4 Supplementary analysis: adverse effects, Outcome 1 Binary outcomes.
4.2
4.2. Analysis
Comparison 4 Supplementary analysis: adverse effects, Outcome 2 Continuous outcomes.
5.1
5.1. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 1 Patient‐reported outcomes that are non‐observable.
5.2
5.2. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 2 Patient‐reported outcomes that are observable.
5.3
5.3. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 3 Observer‐reported outcomes involving patient's cooperation.
5.4
5.4. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 4 Observer‐reported outcomes not involving patient's cooperation.
5.5
5.5. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 5 Laboratory outcomes.
5.6
5.6. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 6 Patient‐reported outcomes that are non‐observable.
5.7
5.7. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 7 Patient‐reported outcomes that are observable.
5.8
5.8. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 8 Observer‐reported outcomes involving patient's cooperation.
5.9
5.9. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 9 Observer‐reported outcomes not involving patient's cooperation.
5.10
5.10. Analysis
Comparison 5 Effect modification subgroup analysis: type of outcomes, Outcome 10 Laboratory outcomes.
6.1
6.1. Analysis
Comparison 6 Effect modification subgroup analysis: the purpose of the trials, Outcome 1 To study the effect of placebo was an explicit trial purpose.
6.2
6.2. Analysis
Comparison 6 Effect modification subgroup analysis: the purpose of the trials, Outcome 2 To study the effect of placebo was not an explicit trial purpose.
6.3
6.3. Analysis
Comparison 6 Effect modification subgroup analysis: the purpose of the trials, Outcome 3 To study the effect of placebo was an explicit trial purpose.
6.4
6.4. Analysis
Comparison 6 Effect modification subgroup analysis: the purpose of the trials, Outcome 4 To study the effect of placebo was not an explicit trial purpose.
7.1
7.1. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 1 Psychological placebos.
7.2
7.2. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 2 Physical placebos.
7.3
7.3. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 3 Pharmacological placebos.
7.4
7.4. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 4 Psychological placebos.
7.5
7.5. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 5 Physical placebos.
7.6
7.6. Analysis
Comparison 7 Effect modification subgroup analysis: type of placebo interventions, Outcome 6 Pharmacological placebos.
8.1
8.1. Analysis
Comparison 8 Effect modification subgroup analysis: patient information, Outcome 1 Binary outcomes: patients not informed that the trial involved placebo.
8.2
8.2. Analysis
Comparison 8 Effect modification subgroup analysis: patient information, Outcome 2 Binary outcomes: patients informed that the trial involved placebo (or not stated).
8.3
8.3. Analysis
Comparison 8 Effect modification subgroup analysis: patient information, Outcome 3 Continuous outcomes: patients not informed that the trial involved placebo.
8.4
8.4. Analysis
Comparison 8 Effect modification subgroup analysis: patient information, Outcome 4 Continuous outcomes: patients informed that the trial involved placebo (or not stated).
9.1
9.1. Analysis
Comparison 9 Effect modification subgroup analysis: placebo as add‐on treatment, Outcome 1 Add‐on treatment: yes.
9.2
9.2. Analysis
Comparison 9 Effect modification subgroup analysis: placebo as add‐on treatment, Outcome 2 Add‐on treatment: no or not stated.
9.3
9.3. Analysis
Comparison 9 Effect modification subgroup analysis: placebo as add‐on treatment, Outcome 3 Add‐on treatment: yes.
9.4
9.4. Analysis
Comparison 9 Effect modification subgroup analysis: placebo as add‐on treatment, Outcome 4 Add‐on treatment: no or not stated.
10.1
10.1. Analysis
Comparison 10 Risk of bias subgroup analysis: blinding of placebo treatment providers, Outcome 1 Placebo intervention provider blinded: yes.
10.2
10.2. Analysis
Comparison 10 Risk of bias subgroup analysis: blinding of placebo treatment providers, Outcome 2 Placebo intervention provider blinded: no or not stated.
10.3
10.3. Analysis
Comparison 10 Risk of bias subgroup analysis: blinding of placebo treatment providers, Outcome 3 Placebo intervention provider blinded: yes.
10.4
10.4. Analysis
Comparison 10 Risk of bias subgroup analysis: blinding of placebo treatment providers, Outcome 4 Placebo intervention provider blinded: no or not stated.
11.1
11.1. Analysis
Comparison 11 Risk of bias subgroup analysis: blinding of observer, Outcome 1 Blinding of observer: yes.
11.2
11.2. Analysis
Comparison 11 Risk of bias subgroup analysis: blinding of observer, Outcome 2 Blinding of observer: not stated.
11.3
11.3. Analysis
Comparison 11 Risk of bias subgroup analysis: blinding of observer, Outcome 3 Blinding of observer: yes.
11.4
11.4. Analysis
Comparison 11 Risk of bias subgroup analysis: blinding of observer, Outcome 4 Blinding of observer: not stated.
12.1
12.1. Analysis
Comparison 12 Risk of bias subgroup analysis: variance inequality and skewness, Outcome 1 No signs of unequal variance or skewness.
12.2
12.2. Analysis
Comparison 12 Risk of bias subgroup analysis: variance inequality and skewness, Outcome 2 Signs of either unequal variance or skewness.
13.1
13.1. Analysis
Comparison 13 Risk of bias subgroup analysis: selection of outcome, Outcome 1 Selection of outcome: primary trial outcome clearly indicated.
13.2
13.2. Analysis
Comparison 13 Risk of bias subgroup analysis: selection of outcome, Outcome 2 Selection of outcome: primary trial outcome not clearly indicated (or not selected).
13.3
13.3. Analysis
Comparison 13 Risk of bias subgroup analysis: selection of outcome, Outcome 3 Selection of outcome: primary trial outcome clearly indicated.
13.4
13.4. Analysis
Comparison 13 Risk of bias subgroup analysis: selection of outcome, Outcome 4 Selection of outcome: primary trial outcome not clearly indicated (or not selected).
14.1
14.1. Analysis
Comparison 14 Risk of bias subgroup analysis: format of outcome, Outcome 1 Outcome was final values.
14.2
14.2. Analysis
Comparison 14 Risk of bias subgroup analysis: format of outcome, Outcome 2 Outcome was change from baseline.
15.1
15.1. Analysis
Comparison 15 Risk of bias subgroup analysis: concealed allocation, Outcome 1 Concealed allocation adequate.
15.2
15.2. Analysis
Comparison 15 Risk of bias subgroup analysis: concealed allocation, Outcome 2 Concealed allocation unclear.
15.3
15.3. Analysis
Comparison 15 Risk of bias subgroup analysis: concealed allocation, Outcome 3 Concealed allocation adequate.
15.4
15.4. Analysis
Comparison 15 Risk of bias subgroup analysis: concealed allocation, Outcome 4 Concealed allocation unclear.
16.1
16.1. Analysis
Comparison 16 Risk of bias subgroup analysis: trial size, Outcome 1 Trial size >49.
16.2
16.2. Analysis
Comparison 16 Risk of bias subgroup analysis: trial size, Outcome 2 Trial size 49 or less.
16.3
16.3. Analysis
Comparison 16 Risk of bias subgroup analysis: trial size, Outcome 3 Trial size >49.
16.4
16.4. Analysis
Comparison 16 Risk of bias subgroup analysis: trial size, Outcome 4 Trial size 49 or less.
17.1
17.1. Analysis
Comparison 17 Risk of bias subgroup analysis: dropouts, Outcome 1 Dropout rates no more than 15%.
17.2
17.2. Analysis
Comparison 17 Risk of bias subgroup analysis: dropouts, Outcome 2 Dropout rates >15%, or not stated.
17.3
17.3. Analysis
Comparison 17 Risk of bias subgroup analysis: dropouts, Outcome 3 Dropout rates no more than 15%.
17.4
17.4. Analysis
Comparison 17 Risk of bias subgroup analysis: dropouts, Outcome 4 Dropout rates > 15%, or not stated.
18.1
18.1. Analysis
Comparison 18 Risk of bias subgroup analysis: clearly concealed allocation + trial size >49 + dropout max 15%, Outcome 1 Binary outcomes.
18.2
18.2. Analysis
Comparison 18 Risk of bias subgroup analysis: clearly concealed allocation + trial size >49 + dropout max 15%, Outcome 2 Continuous outcomes.
18.3
18.3. Analysis
Comparison 18 Risk of bias subgroup analysis: clearly concealed allocation + trial size >49 + dropout max 15%, Outcome 3 Pain heterogeneity.
See this image and copyright information in PMC

Update of

Comment in

  • Sind Placebo wirklich nützlich?
    Enck P. Enck P. Dtsch Med Wochenschr. 2011 May;136(18):934. doi: 10.1055/s-0031-1278429. Epub 2011 Apr 27. Dtsch Med Wochenschr. 2011. PMID: 21526456 German. No abstract available.

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Hossmann 1981 {published data only}
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Moffet 1996 {published data only}
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Molsberger 2002 {published data only}
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Moreland 2006 {published data only}
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Morton 1993 {published data only}
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Murphy 1982 {published data only}
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Mussell 1988 {published data only}
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Najnigier 1997 {published data only}
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Nandi 1976 {published data only}
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Naumann 1989 {published data only}
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Nawrocki 1997 {published data only}
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Nicassio 1974 {published data only}
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Nocella 1982 {published data only}
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O'Brien 1996 {published data only}
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Parker 1995 {published and unpublished data}
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Parker 2003 {published data only}
    1. Parker JC, Smarr KL, Slaughter JR, Johnston SK, Priesmeyer ML, Hanson KD, et al. Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive‐behavioral approach. Arthritis and Rheumatism 2003;49:766‐77. - PubMed
Pearl 1956 {published data only}
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Pelham 1992 {published data only}
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Quahagen 1995 {published data only}
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Rabkin 1990 {published data only}
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Rawling 2001 {published data only}
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Reading 1982 {published data only}
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Ristikankare 1999 {published data only}
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Robinson 2001 {published data only}
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Roongpisuthip 1999 {published data only}
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Roscoe 2002 {published data only}
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Roscoe 2005 {published data only}
    1. Roscoe JA, Matteson SE, Morrow GR, Hickok JT, Bushunow P, Griggs J, et al. Acustimulation wrist bands are not effective for the control of chemotherapy‐induced nausea in women with breast cancer. Journal of Pain and Symptom Management 2005;29:376‐84. - PubMed
Rosen 1976 {published data only}
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Rossi 1982 {published data only}
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Roughan 1981 {published data only}
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Rowbotham 1996 {published data only}
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Rupert 1978 {published data only}
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Rybarczyk 1990 {published data only}
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Röschke 2000 {published data only}
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    1. Rösche J. Wolf C, Kögel P, Wagner P, Bech S. Adjuvant whole body acupuncture for major depression. A placebo‐controlled study of patients in standardised mianserintreatment [Adjuvante Ganzkörper‐akupunktur bei Depression. Eine placebokontrollierte Studie unter standardisierter Mianserintherapie]. Nervenartz 1998;69:961‐7. - PubMed
Rösler 2003 {published data only}
    1. Rösler A, Otto B, Schreiber‐Dietrich D, Steinmetz H, Kessler KR. Single‐needle acupuncture alleviates gag reflex during transesophageal eccocardiography: a blinded, randomised, controlled pilot trial. The Journal of Alternative and Complementary Medicine 2003;9:847‐9. - PubMed
Sanders 1990 {published data only}
    1. Sanders G, Tepe R, Maloney P, Reinert O. The effect of spinal manipulation on subjects with acute low back pain: a comparison of visual analog pain scores and serum beta endorphin levels. Journal of Manipulative and Physiological Therapeutics 1990;13(1):58. - PubMed
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Schallreuter 2002 {published data only}
    1. Shallreuter KU, Moore J, Behrens‐Williams S, Panske A, Harari M. Rapid initiation of repigmentation in vitiligo with dead sea climatotherapy in combination with pseudocatalase (PC‐KUS). International Journal of Dermatology 2002;41:482‐7. - PubMed
Scharf 2006 {published data only}
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Scharff 2002 {published data only}
    1. Scharff L, Marcus DA, Masek BJ. A controlled study of minimal‐contact thermal biofeedback treatment in children with migraine. Journal of Pediatric Psychology 2002;27:109‐19. - PubMed
Seer 1980 {published data only}
    1. Seer P, Raeburn JM. Meditation training and essential hypertension: a methodological study. Journal of Behavioral Medicine 1980;3(1):59‐71. [MEDLINE: ] - PubMed
Senediak 1985 {published data only}
    1. Senediak C, Spence SH. Rapid versus gradual scheduling of therapeutic contact in a family based behavioural weight control programme for children. Behavioural Psychotherapy 1985;13:265‐87.
Shen 2000 {published data only}
    1. Shen J, Wenger N, Glaspy J, Hays RD, Albert PS, Choi C, Shekelle PG. Electroacupuncture for control of myeloablative chemotherapy‐induced emesis. JAMA 2000;284:2755‐61. - PubMed
Sibilio 1957 {published data only}
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Sinaiko 1991 {published and unpublished data}
    1. Gómez‐Marín O, Prineas RJ, Sinaiko AR. The sodium‐potassium blood pressure trial in children. Design, recruitment, and randomization: the children and adolescent blood pressure program. Controlled Clinical Trials 1991;12:408‐23. - PubMed
    1. Sinaiko AR, Gómez‐Marín O, Prineas RJ. Effect of low sodium diet or potassium supplementation on adolescent blood pressure. Hypertension 1993; Vol. 21:989‐994. - PubMed
Sipich 1974 {published data only}
    1. Sipich JF, Russell RK, Tobias LL. A comparison of covert sensitization and 'nonspecific' treatment in the modification of smoking behavior. Journal of Behavior Therapy and Experimental Psychiatry 1974;5:201‐3.
Sommerness 1955 {published data only}
    1. Sommerness MD, Lucero RJ, Hamlon JS, Erickson JL, et al. A controlled study of reserpine on chronically disturbed patients. AMA Archives of Neurology and Psychiatry 1955;74:316‐9. - PubMed
Spanos 1995 {published data only}
    1. Spanos NP, Mondoux TJ, Burgess CA. Comparison of multi‐component hypnotic and non‐hypnotic treatments for smoking. Contemporary Hypnosis 1995;12(1):12‐19.
Sprott 1993 {published data only}
    1. Sprott H, Mennet P, Stratz T, Müller W. Efficacy of acupuncture in patients with generalised tendomyopathy (fibromyalgia) [Wirksamkeit der Acupunktur bei Patienten mit generaliserter Tendomyopathie (Fibromyalgie)]. Aktuelle Rheumatologie 1993;18:132‐5.
    1. Sprott H, Müller W. Efficacy of acupuncture in patients with fibromyalgia. Reumatologia 1994;32(4):414‐21.
Stabholz 1991 {published data only}
    1. Stabholz A, Shapira J, Shur D, Friedman M, et al. Local application of sustained‐release delivery system of chlorhexidine in Down's syndrome population. Clinical Preventive Dentistry 1991;13(5):9‐14. [MEDLINE: ] - PubMed
Steinsbekk 2004 {published data only}
    1. Steinsbekk A, Bentzen N, Fønnebø V, Lewith G. Self treatment with one of three self selected, ultramelecular homeopathic medicines for the prevention of upper respiratory tract infections in children. A double‐blind randomized placebo controlled trial. British Journal of Clinical Pharmacology 2005;59:447‐55. - PMC - PubMed
    1. Steinsbekk A, Bentzen N, Fønnebø V, Lewith GT. Homeopathic care for the prevention of upper respiratory tract infections in children: A double‐blind randomized placebo controlled trial comparing individualised homeopathic care and waiting‐list controls. Complemantary Therapies in Medicine 2005;13:231‐8. - PubMed
    1. Steinsbekk A, Bentzen N, Fønnebø V, Lewith GT. Randomzed controlled trial on treatment by homeopaths and self‐treatment with homeopathic medicines: design and protocol. Journal of Alternative and Complementary Medecine 2004;10:1027‐32. - PubMed
Stewart 1991 {published data only}
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Stransky 1989 {published data only}
    1. Stransky M, Rubin A, Lava NS, Lazaro RP. Treatment of carpal tunnel syndrome with vitamin B6: a double‐blind study. Southern Medical Journal 1989;89(7):841‐2. [MEDLINE: ] - PubMed
Straub 2001 {published data only}
    1. Straub WF, Spino MP, Alattar MM, Pfleger B, et al. The effect of chiropractic care on jet lag of Finnish junior elite athletes. Journal of Manipulative and Physiological Therapeutics 2001;24:191‐8. - PubMed
Sumaya 2001 {published data only}
    1. Sumaya IC, Rienzi BM, Deegan JF, Moss DE. Bright light treatment decreases depression in institutionalized older adults: a placebo‐controlled crossover study. The Journals of Gerontology. Series A. Biological Sciences and Medical Sciences 2001;56A:M356‐60. - PubMed
Tan 1982 {published data only}
    1. Tan SY, Poser EG. Acute pain in a clinical setting: effects of cognitive‐behavioural skills training. Behaviour Research and Therapy 1982;20:535‐45. [MEDLINE: ] - PubMed
Tan 1986 {published data only}
    1. Tan SY, Bruni J. Cognitive‐behavior therapy with adult patients with epilepsy: a controlled outcome study. Epilepsia 1986;27(3):225‐32. [MEDLINE: ] - PubMed
Tarcin 2004 {published data only}
    1. Tarcin O, Gurbuz AK, Pocan S, Keskin O, Demirturk L. Acustimulation of the Neiguan point during gastroscopy: its effects on nausea and retching. Turkish Journal of Gastroenterology 2004;15:258‐62. - PubMed
Tarrier 1998 {published data only}
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Tashjian 2006 {published data only}
    1. Tashjian RZ, Banerjee R, Bradley MP, Alford W, Fadale PD. Zolpidem reduces postoperative pain, fatigue, and narcotic consumption following knee arthroscopy: a prospective randomized placebo‐controlled double‐blinded study. Journal of Knee Surgery 2006;19:105‐11. - PubMed
Theroux 1993 {published data only}
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Thomas 1987 {published data only}
    1. Thomas KB. General practice consultations: is there any point in being positive?. British Medical Journal 1987;294:1200‐2. [MEDLINE: ] - PMC - PubMed
Thomas 1999 {published data only}
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Thomas 2002a {published data only}
    1. Thomas KS, Muir KR, Doherty M, Jones AC, O'Reilly SC, Bassey EJ. Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial. BMJ 2002;325:752‐7. - PMC - PubMed
Thomas 2002b {published data only}
    1. Thomas KS, Muir KR, Doherty M, Jones AC, O'Reilly SC, Bassey EJ. Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial. BMJ 2002;325:752‐7. - PMC - PubMed
Tremeau 1992 {published data only}
    1. Tremeau ML, Fontanie‐Ravier P, Teurnier F, Demouzon J. Protocol of cervical maturation by acupuncture [Protocole de maturation cervicale par acupuncture]. Journal de Gynecologie Obstetrique et Biologie de la Reproduction 1992;21:375‐80. [MEDLINE: ] - PubMed
Tritrakarn 2000 {published data only}
    1. Tritrakarn T, Lertakyamanee J, Koompong P, Soontrapa S, Somprakit P, Tantiwong A, Jittapapai S. Both EMLA and placebo cream reduced pain during extracorporeal piezoelectric scock wave lithotripsy with the piezolith 2300. Anaesthesiology 2000;92:1049‐54. - PubMed
Tsay 2003 {published data only}
    1. Tsay SL, Chen ML. Acupressure and quality of sleep in patients with end‐stage renal disease: a randomised controlled trial. International Journal of Nursing Studies 2003;40(1):1‐7. - PubMed
Tsay 2004 {published data only}
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Tuomilehto 1980 {published data only}
    1. Tuomilehto J, Voutilainen E, Huttunen J, Vinni S, et al. Effect of guar gum on body weight and serum lipids in hypercholesterolemic females. Acta Medica Scandinavica 1980;208:45‐8. [MEDLINE: ] - PubMed
Turner 1979 {published data only}
    1. Ascher ML, Turner RM. A comparison of two methods for the administration of paradoxical intention. Behaviour Research and Therapy 1980;18:121‐6. [MEDLINE: ] - PubMed
    1. Turner RM, Ascher LM. Controlled comparison of progressive relaxation, stimulus control, and paradoxical intention therapies for insomnia. Journal of Consulting and Clinical Psychology 1979;47(3):500‐8. [MEDLINE: ] - PubMed
Tyler 1946 {published data only}
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Vlaeyen 1996 {published data only}
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Walton 1993 {published data only}
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Wang 1997 {published data only}
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Watzl 1986 {published data only}
    1. Watzl H, Olbrich R, Rist F, Cohen R. Placebo injections and alcohol surveillance in inpatient treatment of alcoholic women: An experimental study of two treatment characteristics [Placebo‐injektionen und Alkoholkontrollen in der stationären Behandlung alkoholkranker Frauen ‐ eine experimentelle Untersuchung zweier Behandlungsmerkmale]. Zeitschrift für Klinische Psychologie 1986;15(4):333‐45.
Weingaertner 1971 {published data only}
    1. Weingaertner AH. Self‐administered aversive stimulation with hallucinating hospitalized schizophrenics. Journal of Consulting and Clinical Psychology 1971;36(3):422‐9. [MEDLINE: ] - PubMed
Werntoft 2001 {published data only}
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Whittaker 1963 {published data only}
    1. Whittaker CB, Hoy RM. Withdrawal of perphenazine in chronic schizophrenia. The British Journal of Psychiatry; the Journal of Mental Science 1963;109:422‐7. - PubMed
Wilcock 2008 {published data only}
    1. Wilcock A, Walton A, Manderson C, Feathers L, Khoury B, Lewis M, et al. Randomised, placebo‐controlled trial of nebulised furosamide for breathlessness in patients with cancer. Thorax 2008;63:872‐5. [DOI: 10.1136/thx.2007.091538] - DOI - PubMed
Williams 1988 {published data only}
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Wilson 1980 {published data only}
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Witt 2005 {published data only}
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Wojciechowski 1984 {published data only}
    1. Wojciechowski FL. Behavioral treatment of tension headache: a contribution to controlled outcome research methodology. Gedrag ‐ Tijdschrift voor Psychologie 1984;12(5):16‐30.
Woods 2005 {published data only}
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Yan 2005 {published data only}
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    1. Yan T, Hui‐chan CWY, Li LSW. Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke. Stroke 2005;36:80‐85. - PubMed
Yates 1988 {published data only}
    1. Yates RG, Lamping DL, Abram NL, Wright C. Effects of chiropractic treatment on blood pressure and anxiety: a randomized, controlled trial. Journal of Manipulative and Physiological Therapeutics 1988;11(6):484‐8. [MEDLINE: ] - PubMed

References to studies excluded from this review

Abbot 1995 {published data only}
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Allen 1987 {published data only}
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Allen 1996 {published and unpublished data}
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Arnett 1990 {published data only}
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Babizhayev 2001 {published data only}
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Barrett 1999 {published data only}
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Beck 2002 {published data only}
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Benedetti 1998 {published data only}
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Benedetti 1999b {published data only}
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Benedict 1989 {published data only}
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Bennet 2001 {published data only}
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Bergmann 1994 {published data only}
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Beutler 1988 {published data only}
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Dobia 1985 {published data only}
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Dundee 1988 {published data only}
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Eickholz 2002 {published data only}
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Elkin 1985 {published data only}
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Feather 1972 {published data only}
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Fevery 1990 {published data only}
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Fillmore 1992 {published data only}
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Fillmore 1994 {published data only}
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Fillmore 1994b {published data only}
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Flor 1983 {published data only}
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Gam 1998 {published data only}
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Gryll 1978 {published data only}
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Haake 2007 {published data only}
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Hall 1994 {published data only}
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Hargreaves 1983 {published data only}
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Hayden 1996 {published data only}
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Jensen 1991 {published data only}
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Kanner 1999 {published data only}
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Kelley 1976 {published data only}
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Khandwala 1997 {published and unpublished data}
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Klosko 1990 {published data only}
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Korner 1982 {published data only}
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Lasagna 1954 {published data only}
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Levine 1980 {published data only}
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Liberman 1964 {published data only}
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Lopez 1999 {published data only}
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Lorr 1962 {published data only}
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Lujan 1992 {published data only}
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Lynn 1983 {published and unpublished data}
    1. Lynn FE. Acupressure for the treatment of menstrual distress. PhD‐thesis, University of California 1983.
Manner 1987 {published data only}
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Marchand 1993 {published data only}
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McGrath 1988 {published data only}
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Meehan 1985 {published data only}
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Montgomery 1996 {published data only}
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Nikolaou 1998 {published data only}
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Peart 1977 {published data only}
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Robertson 1991 {published data only}
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Rodriguez 1997 {published data only}
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Roehrich 1993 {published data only}
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Roelofs 2000 {published data only}
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References to studies awaiting assessment

References to ongoing studies

Barret 2007 {published data only}
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