Placebo effects

People who believe that a treatment will help to relieve their symptoms may well experience improvements in their condition – even though the treatment, in fact, has no active ingredient.

JLL Essay

1.2 Why treatment comparisons are essential

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Papin D (1704)
123. Papin an Leibniz. In: Gerland E (1881) Leibnizens und Huygens’ Briefwechsel mit Papin. Berlin:Verlag der Koniglichen Akademie der Wissenschaften. p 328.

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Smellie W (1752)
A treatise on the theory and practice of Midwifery. 2nd edition. London: D. Wilson, T Durham, p 224.

View

Pierce R (1763)
Quoted in Sutherland A. Attempts to revive ancient medical doctrines Volume 1. London: A Millar, pp xxiii-xxiv.

View

Cullen W (1772)
Clinical lectures. Edinburgh, Feb-April, 218-219.

View

Commission Royale. Bailly A (1784)
Rapport des commissaires chargés par le Roi, de l'examen du magnétisme animale [Report of the Comissioners required by the King to examine animal magnetism]. Imprimé par ordre du Roi. Paris: A Paris, de L'Imprimerie Royale.

View

Gordon A (1788)
The practice of physick. Unpublished manuscript.

View

Hunter J (1788)
A treatise on the venereal disease. London: G Nicol and J Johnson, pp 69-70.

View

Trotter T (1792)
Observations on the scurvy. London: Longman, pp 137-138, 184.

View

Ministry of Internal Affairs (1832)
[Conclusion of the Medical Council regarding homeopathic treatment] . Zhurnal Ministerstva Vnutrennih del;3:49-63.

View

Hunter J (1835)
The works of John Hunter FRS, edited by James F Palmer, Vol 1. London: Longman et al., p 360.

View

Forbes J (1846)
Homoeopathy, allopathy and “young physic”. British and Foreign Medical Review 225-265.

View

Flint A (1863)
A contribution toward the natural history of articular rheumatism; consisting of a report of thirteen cases treated solely with palliative measures. American Journal of the Medical Sciences 46:17-36.

View

Sutton HG (1865)
Cases of rheumatic fever treated for the most part by mint water. Guy’s Hospital Reports 2:392-428.

View

Anonymous (1890)
The placebo in medicine. Medical Press 1890:18th June p642.

View

Moll A (1891)
Hypnotism. London: Walter Scott, p 224.

View

Rivers WHR (1908)
The influence of alcohol and other drugs on fatigue. London: Edward Arnold.

View

Riseman JEF, Brown MG (1937)
Medicinal treatment of angina pectoris. Archives of Internal Medicine 60:100-118.

View

Bahnsen P, Jacobsen E, Thesleff H (1938)
Studien über die Wirkung von beta-phenyl-isopropylaminsulfdat (Mecodrin) auf normale Menschen. [Studies on the effect of beta-phenyl-isopropylaminsulfdat (Mecodrin) on normal volunteers]. Klinische Wochenschrift 17:1074-1078.

View

Rinzler SH, Bakst H, Benjamin Z, Bobb AL, Travell J (1950)
Failure of alpha tocopherol to influence chest pain in patients with heart disease. Circulation 1:288-293.

View

Rinzler SH, Travell J, Bakst H, Benjamin ZH, Rosenthal RL, Rosenfeld S, Hirsch BB (1953)
Effect of heparin in effort angina. American Journal of Medicine 14:438-447.

View

Greiner T, Bross I, Gold H (1957)
A method for evaluation of laxative habits in human subjects. Journal of Chronic Diseases 6:244-255.

View

Kerr DNS, Davidson S (1958)
Gastrointestinal intolerance to oral iron preparations. Lancet 2:489-492.

View

Gracely RH, Dubner R, Deeter WR, Wolskee PJ (1985)
Clinicians’ expectations influence placebo analgesia. Lancet 325:43. DOI:https://doi.org/10.1016/S0140-6736(85)90984-5

View

Waller LA (1997)
A note on Harold S Diehl, randomization, and clinical trials. Controlled Clinical Trials 18: 180-183.

View

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJF, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ (2014)
Use of placebo controls in the evaluation of surgery: systematic review. BMJ 348:g3253. doi: 10.1136/bmj.g3253.

View

Wartolowska KA, Collins GS, Hopewell S, Judge A, Dean BJF, Rombach I, Beard DJ, Carr AJ (2016)
Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review. BMJ Open 6: p.e010194.

View

Moustgaard H, Clayton GL, Jones HE, Boutron I, Jørgensen L, Laursen DRT, Olsen MF, Paludan-Müller A, Ravaud P, Savović J, Sterne JAC, Higgins JPT, Hróbjartsson A (2020)
Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ 368, l6802.

View

D'Aquila RT, Hughes MD, Johnson VA, Fischl MA, Sommadossi JP, Liou SH, Timpone J, Myers M, Basgoz N, Niu M, Hirsch MS (2021)
Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double- blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Annals of Internal Medicine 124:1019-1030.

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Faltinsen E, Todorovac A, Staxen Bruun L, Hróbjartsson A, Gluud C, Kongerslev MT, Simonsen E, Storebø OJ (2022)
Control interventions in randomised trials among people with mental health disorders. Cochrane Database of Systematic Reviews 4(4):MR000050.

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Laursen DRT, Nejstgaard CH, Bjørkedal E, Frost AD, Hansen MR, Paludan-Müller AS, Prosenz J, Werner CP, Hróbjartsson A. (2023)
Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo. Cochrane Database of Systematic Reviews 3(3):MR000055.

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Armitage P† (2003).
Some recollections of the early years of the Medical Research Council (MRC) Statistical Research Unit. JLL Bulletin: Commentaries on the history of treatment evaluation.

View

Marson Smith P, Colquhoun D, Chalmers I (2019).
John Henry Gaddum’s 1940 guidance on controlled clinical trials JLL Bulletin: Commentaries on the history of treatment evaluation.

View

Senn SJ, Chalmers I (2021).
Giving and taking: ethical treatment assignment in controlled trials. JLL Bulletin: Commentaries on the history of treatment evaluation.

View

Podolsky SH (2022).
The (Harry) Gold Standard: angina, suggestion, and the path to the “double-blind” test and Clinical Pharmacology. JLL Bulletin: Commentaries on the history of treatment evaluation.

View

Glasziou P, Matthews R, Boutron I, Chalmers I, Armitage P† (2023)
The differences and overlaps between ‘explanatory’ and ‘pragmatic’ controlled trials: a historical perspective. JLL Bulletin: Commentaries on the history of treatment evaluation.

View

Quiz: Why Treatment Comparisons Are Essential

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Topics

The need to address treatment uncertainties

Principles of Testing

Treatment comparisons are essential

Treatment comparisons must be fair

Biases

Double dummy

The play of chance

Bringing it all together for the benefit of patients and the public

James Lind LibraryIllustrating the development of fair tests of treatments in health care

Placebo effects

SORT date ▲ author

30 RECORDS

5 ARTICLES

1 BLOG

Papin D (1704) 123. Papin an Leibniz. In: Gerland E (1881) Leibnizens und Huygens’ Briefwechsel mit Papin. Berlin:Verlag der Koniglichen Akademie der Wissenschaften. p 328.

Smellie W (1752) A treatise on the theory and practice of Midwifery. 2nd edition. London: D. Wilson, T Durham, p 224.

Pierce R (1763) Quoted in Sutherland A. Attempts to revive ancient medical doctrines Volume 1. London: A Millar, pp xxiii-xxiv.

Cullen W (1772) Clinical lectures. Edinburgh, Feb-April, 218-219.

Commission Royale. Bailly A (1784) Rapport des commissaires chargés par le Roi, de l'examen du magnétisme animale [Report of the Comissioners required by the King to examine animal magnetism]. Imprimé par ordre du Roi. Paris: A Paris, de L'Imprimerie Royale.

Gordon A (1788) The practice of physick. Unpublished manuscript.

Hunter J (1788) A treatise on the venereal disease. London: G Nicol and J Johnson, pp 69-70.

Trotter T (1792) Observations on the scurvy. London: Longman, pp 137-138, 184.

Ministry of Internal Affairs (1832) [Conclusion of the Medical Council regarding homeopathic treatment] . Zhurnal Ministerstva Vnutrennih del;3:49-63.

Hunter J (1835) The works of John Hunter FRS, edited by James F Palmer, Vol 1. London: Longman et al., p 360.

Forbes J (1846) Homoeopathy, allopathy and “young physic”. British and Foreign Medical Review 225-265.

Flint A (1863) A contribution toward the natural history of articular rheumatism; consisting of a report of thirteen cases treated solely with palliative measures. American Journal of the Medical Sciences 46:17-36.

Sutton HG (1865) Cases of rheumatic fever treated for the most part by mint water. Guy’s Hospital Reports 2:392-428.

Anonymous (1890) The placebo in medicine. Medical Press 1890:18th June p642.

Moll A (1891) Hypnotism. London: Walter Scott, p 224.

Rivers WHR (1908) The influence of alcohol and other drugs on fatigue. London: Edward Arnold.

Riseman JEF, Brown MG (1937) Medicinal treatment of angina pectoris. Archives of Internal Medicine 60:100-118.

Bahnsen P, Jacobsen E, Thesleff H (1938) Studien über die Wirkung von beta-phenyl-isopropylaminsulfdat (Mecodrin) auf normale Menschen. [Studies on the effect of beta-phenyl-isopropylaminsulfdat (Mecodrin) on normal volunteers]. Klinische Wochenschrift 17:1074-1078.

Rinzler SH, Bakst H, Benjamin Z, Bobb AL, Travell J (1950) Failure of alpha tocopherol to influence chest pain in patients with heart disease. Circulation 1:288-293.

Rinzler SH, Travell J, Bakst H, Benjamin ZH, Rosenthal RL, Rosenfeld S, Hirsch BB (1953) Effect of heparin in effort angina. American Journal of Medicine 14:438-447.

Greiner T, Bross I, Gold H (1957) A method for evaluation of laxative habits in human subjects. Journal of Chronic Diseases 6:244-255.

Kerr DNS, Davidson S (1958) Gastrointestinal intolerance to oral iron preparations. Lancet 2:489-492.

Gracely RH, Dubner R, Deeter WR, Wolskee PJ (1985) Clinicians’ expectations influence placebo analgesia. Lancet 325:43. DOI:https://doi.org/10.1016/S0140-6736(85)90984-5

Waller LA (1997) A note on Harold S Diehl, randomization, and clinical trials. Controlled Clinical Trials 18: 180-183.

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJF, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ (2014) Use of placebo controls in the evaluation of surgery: systematic review. BMJ 348:g3253. doi: 10.1136/bmj.g3253.

Wartolowska KA, Collins GS, Hopewell S, Judge A, Dean BJF, Rombach I, Beard DJ, Carr AJ (2016) Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review. BMJ Open 6: p.e010194.

Moustgaard H, Clayton GL, Jones HE, Boutron I, Jørgensen L, Laursen DRT, Olsen MF, Paludan-Müller A, Ravaud P, Savović J, Sterne JAC, Higgins JPT, Hróbjartsson A (2020) Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ 368, l6802.

Faltinsen E, Todorovac A, Staxen Bruun L, Hróbjartsson A, Gluud C, Kongerslev MT, Simonsen E, Storebø OJ (2022) Control interventions in randomised trials among people with mental health disorders. Cochrane Database of Systematic Reviews 4(4):MR000050.

Show ALL ARTICLES Brief histories Commentaries Biographies Personal reflections Doctoral theses

Armitage P† (2003).Some recollections of the early years of the Medical Research Council (MRC) Statistical Research Unit. JLL Bulletin: Commentaries on the history of treatment evaluation.

Marson Smith P, Colquhoun D, Chalmers I (2019).John Henry Gaddum’s 1940 guidance on controlled clinical trials JLL Bulletin: Commentaries on the history of treatment evaluation.

Senn SJ, Chalmers I (2021).Giving and taking: ethical treatment assignment in controlled trials. JLL Bulletin: Commentaries on the history of treatment evaluation.

Podolsky SH (2022).The (Harry) Gold Standard: angina, suggestion, and the path to the “double-blind” test and Clinical Pharmacology. JLL Bulletin: Commentaries on the history of treatment evaluation.

Glasziou P, Matthews R, Boutron I, Chalmers I, Armitage P† (2023)The differences and overlaps between ‘explanatory’ and ‘pragmatic’ controlled trials: a historical perspective. JLL Bulletin: Commentaries on the history of treatment evaluation.

Quiz: Why Treatment Comparisons Are Essential

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James Lind Library
Illustrating the development of fair tests of treatments in health care

Papin D (1704)
123. Papin an Leibniz. In: Gerland E (1881) Leibnizens und Huygens’ Briefwechsel mit Papin. Berlin:Verlag der Koniglichen Akademie der Wissenschaften. p 328.

Smellie W (1752)
A treatise on the theory and practice of Midwifery. 2nd edition. London: D. Wilson, T Durham, p 224.

Pierce R (1763)
Quoted in Sutherland A. Attempts to revive ancient medical doctrines Volume 1. London: A Millar, pp xxiii-xxiv.

Cullen W (1772)
Clinical lectures. Edinburgh, Feb-April, 218-219.

Commission Royale. Bailly A (1784)
Rapport des commissaires chargés par le Roi, de l'examen du magnétisme animale [Report of the Comissioners required by the King to examine animal magnetism]. Imprimé par ordre du Roi. Paris: A Paris, de L'Imprimerie Royale.

Gordon A (1788)
The practice of physick. Unpublished manuscript.

Hunter J (1788)
A treatise on the venereal disease. London: G Nicol and J Johnson, pp 69-70.

Trotter T (1792)
Observations on the scurvy. London: Longman, pp 137-138, 184.

Ministry of Internal Affairs (1832)
[Conclusion of the Medical Council regarding homeopathic treatment] . Zhurnal Ministerstva Vnutrennih del;3:49-63.

Hunter J (1835)
The works of John Hunter FRS, edited by James F Palmer, Vol 1. London: Longman et al., p 360.

Forbes J (1846)
Homoeopathy, allopathy and “young physic”. British and Foreign Medical Review 225-265.

Flint A (1863)
A contribution toward the natural history of articular rheumatism; consisting of a report of thirteen cases treated solely with palliative measures. American Journal of the Medical Sciences 46:17-36.

Sutton HG (1865)
Cases of rheumatic fever treated for the most part by mint water. Guy’s Hospital Reports 2:392-428.

Anonymous (1890)
The placebo in medicine. Medical Press 1890:18th June p642.

Moll A (1891)
Hypnotism. London: Walter Scott, p 224.

Rivers WHR (1908)
The influence of alcohol and other drugs on fatigue. London: Edward Arnold.

Riseman JEF, Brown MG (1937)
Medicinal treatment of angina pectoris. Archives of Internal Medicine 60:100-118.

Bahnsen P, Jacobsen E, Thesleff H (1938)
Studien über die Wirkung von beta-phenyl-isopropylaminsulfdat (Mecodrin) auf normale Menschen. [Studies on the effect of beta-phenyl-isopropylaminsulfdat (Mecodrin) on normal volunteers]. Klinische Wochenschrift 17:1074-1078.

Rinzler SH, Bakst H, Benjamin Z, Bobb AL, Travell J (1950)
Failure of alpha tocopherol to influence chest pain in patients with heart disease. Circulation 1:288-293.

Rinzler SH, Travell J, Bakst H, Benjamin ZH, Rosenthal RL, Rosenfeld S, Hirsch BB (1953)
Effect of heparin in effort angina. American Journal of Medicine 14:438-447.

Greiner T, Bross I, Gold H (1957)
A method for evaluation of laxative habits in human subjects. Journal of Chronic Diseases 6:244-255.

Kerr DNS, Davidson S (1958)
Gastrointestinal intolerance to oral iron preparations. Lancet 2:489-492.

Gracely RH, Dubner R, Deeter WR, Wolskee PJ (1985)
Clinicians’ expectations influence placebo analgesia. Lancet 325:43. DOI:https://doi.org/10.1016/S0140-6736(85)90984-5

Waller LA (1997)
A note on Harold S Diehl, randomization, and clinical trials. Controlled Clinical Trials 18: 180-183.

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJF, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ (2014)
Use of placebo controls in the evaluation of surgery: systematic review. BMJ 348:g3253. doi: 10.1136/bmj.g3253.

Wartolowska KA, Collins GS, Hopewell S, Judge A, Dean BJF, Rombach I, Beard DJ, Carr AJ (2016)
Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review. BMJ Open 6: p.e010194.

Moustgaard H, Clayton GL, Jones HE, Boutron I, Jørgensen L, Laursen DRT, Olsen MF, Paludan-Müller A, Ravaud P, Savović J, Sterne JAC, Higgins JPT, Hróbjartsson A (2020)
Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ 368, l6802.

Faltinsen E, Todorovac A, Staxen Bruun L, Hróbjartsson A, Gluud C, Kongerslev MT, Simonsen E, Storebø OJ (2022)
Control interventions in randomised trials among people with mental health disorders. Cochrane Database of Systematic Reviews 4(4):MR000050.

Show

Armitage P† (2003).
Some recollections of the early years of the Medical Research Council (MRC) Statistical Research Unit. JLL Bulletin: Commentaries on the history of treatment evaluation.

Marson Smith P, Colquhoun D, Chalmers I (2019).
John Henry Gaddum’s 1940 guidance on controlled clinical trials JLL Bulletin: Commentaries on the history of treatment evaluation.

Senn SJ, Chalmers I (2021).
Giving and taking: ethical treatment assignment in controlled trials. JLL Bulletin: Commentaries on the history of treatment evaluation.

Podolsky SH (2022).
The (Harry) Gold Standard: angina, suggestion, and the path to the “double-blind” test and Clinical Pharmacology. JLL Bulletin: Commentaries on the history of treatment evaluation.

Glasziou P, Matthews R, Boutron I, Chalmers I, Armitage P† (2023)
The differences and overlaps between ‘explanatory’ and ‘pragmatic’ controlled trials: a historical perspective. JLL Bulletin: Commentaries on the history of treatment evaluation.