Contextual Effects: How To, and How Not To, Quantify Them

Overview

Journal BMC Med Res Methodol

Publisher Biomed Central

Specialties General Medicine
Health Services

Date 2024 Feb 13

PMID 38350852

Authors

Tobias Saueressig

Hugo Pedder

Patrick J Owen

Daniel L Belavy

Affiliations

Soon will be listed here.

Abstract

The importance of contextual effects and their roles in clinical care controversial. A Cochrane review published in 2010 concluded that placebo interventions lack important clinical effects overall, but that placebo interventions can influence patient-reported outcomes such as pain and nausea. However, systematic reviews published after 2010 estimated greater contextual effects than the Cochrane review, which stems from the inappropriate methods employed to quantify contextual effects. The effects of medical interventions (i.e., the total treatment effect) can be divided into three components: specific, contextual, and non-specific. We propose that the most effective method for quantifying the magnitude of contextual effects is to calculate the difference in outcome measures between a group treated with placebo and a non-treated control group. Here, we show that other methods, such as solely using the placebo control arm or calculation of a 'proportional contextual effect,' are limited and should not be applied. The aim of this study is to provide clear guidance on best practices for estimating contextual effects in clinical research.

Citing Articles

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References

Kessels R, Mozer R, Bloemers J . Methods for assessing and controlling placebo effects. Stat Methods Med Res. 2017; 28(4):1141-1156. DOI: 10.1177/0962280217748339. View

Simon G, Shortreed S, DeBar L . Zelen design clinical trials: why, when, and how. Trials. 2021; 22(1):541. PMC: 8371763. DOI: 10.1186/s13063-021-05517-w. View

Wartolowska K, Gerry S, Feakins B, Collins G, Cook J, Judge A . A meta-analysis of temporal changes of response in the placebo arm of surgical randomized controlled trials: an update. Trials. 2017; 18(1):323. PMC: 5508709. DOI: 10.1186/s13063-017-2070-9. View

Camerone E, Piedimonte A, Testa M, Wiech K, Vase L, Zamfira D . The Effect of Temporal Information on Placebo Analgesia and Nocebo Hyperalgesia. Psychosom Med. 2020; 83(1):43-50. DOI: 10.1097/PSY.0000000000000882. View

Maher C, Traeger A, Abdel Shaheed C, OKeeffe M . Placebos in clinical care: a suggestion beyond the evidence. Med J Aust. 2021; . PMC: 9293195. DOI: 10.5694/mja2.51230. View

Enck P, Bingel U, Schedlowski M, Rief W . The placebo response in medicine: minimize, maximize or personalize?. Nat Rev Drug Discov. 2013; 12(3):191-204. DOI: 10.1038/nrd3923. View

Friedrich J, Adhikari N, Beyene J . Ratio of means for analyzing continuous outcomes in meta-analysis performed as well as mean difference methods. J Clin Epidemiol. 2011; 64(5):556-64. DOI: 10.1016/j.jclinepi.2010.09.016. View

Mainka T, Erro R, Rothwell J, Kuhn A, Bhatia K, Ganos C . Remission in dystonia - Systematic review of the literature and meta-analysis. Parkinsonism Relat Disord. 2019; 66:9-15. DOI: 10.1016/j.parkreldis.2019.02.020. View

Hrobjartsson A, Gotzsche P . Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010; (1):CD003974. PMC: 7156905. DOI: 10.1002/14651858.CD003974.pub3. View

10.

Coleshill M, Sharpe L, Colloca L, Zachariae R, Colagiuri B . Placebo and Active Treatment Additivity in Placebo Analgesia: Research to Date and Future Directions. Int Rev Neurobiol. 2018; 139:407-441. PMC: 6179351. DOI: 10.1016/bs.irn.2018.07.021. View

11.

Kaptchuk T, Hemond C, Miller F . Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. BMJ. 2020; 370:m1668. DOI: 10.1136/bmj.m1668. View

12.

Friedrich J, Adhikari N, Beyene J . The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: a simulation study. BMC Med Res Methodol. 2008; 8:32. PMC: 2430201. DOI: 10.1186/1471-2288-8-32. View

13.

Altman D, Royston P . The cost of dichotomising continuous variables. BMJ. 2006; 332(7549):1080. PMC: 1458573. DOI: 10.1136/bmj.332.7549.1080. View

14.

Kirsch I . Are drug and placebo effects in depression additive?. Biol Psychiatry. 2000; 47(8):733-5. DOI: 10.1016/s0006-3223(00)00832-5. View

15.

Wartolowska K, Feakins B, Collins G, Cook J, Judge A, Rombach I . The magnitude and temporal changes of response in the placebo arm of surgical randomized controlled trials: a systematic review and meta-analysis. Trials. 2016; 17(1):589. PMC: 5154040. DOI: 10.1186/s13063-016-1720-7. View

16.

Zou K, Wong J, Abdullah N, Chen X, Smith T, Doherty M . Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2016; 75(11):1964-1970. PMC: 5099197. DOI: 10.1136/annrheumdis-2015-208387. View

17.

Nikolakopoulou A, Chaimani A, Furukawa T, Papakonstantinou T, Rucker G, Schwarzer G . When does the placebo effect have an impact on network meta-analysis results?. BMJ Evid Based Med. 2023; 29(2):127-134. PMC: 10982636. DOI: 10.1136/bmjebm-2022-112197. View

18.

Benedetti F . Mechanisms of placebo and placebo-related effects across diseases and treatments. Annu Rev Pharmacol Toxicol. 2007; 48:33-60. DOI: 10.1146/annurev.pharmtox.48.113006.094711. View

19.

Testa M, Rossettini G . Enhance placebo, avoid nocebo: How contextual factors affect physiotherapy outcomes. Man Ther. 2016; 24:65-74. DOI: 10.1016/j.math.2016.04.006. View

20.

Dworkin R, Evans S, Mbowe O, McDermott M . Essential statistical principles of clinical trials of pain treatments. Pain Rep. 2021; 6(1):e863. PMC: 7837867. DOI: 10.1097/PR9.0000000000000863. View