Methods for assessing and controlling placebo effects

Kessels, Rob; Mozer, Reagan; Bloemers, Jos

doi:10.1177/0962280217748339

Cited by 13 publications

(18 citation statements)

References 81 publications

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“…This argument though is not straightforward as the placebo response may differ between arms of a trial and there are statistical models that seek to overcome this issue 8. There are also trial designs that attempt to manage the placebo response 8–10. Evidence regarding the benefit of these strategies is not always clear 10…”

Section: Introductionmentioning

confidence: 99%

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

Rojí

Stone

Ricciardi

et al. 2020

BMJ Support Palliat Care

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BackgroundCancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors.MethodRCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool.ResultsFrom 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR.ConclusionThere is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.

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Section: Introductionmentioning

confidence: 99%

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

Rojí

Stone

Ricciardi

et al. 2020

BMJ Support Palliat Care

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“…Lastly, in this study, we used response as our primary outcome. We assumed that placebo response is a stable trait and classified response pattern into response and non-response as many previous models did,32 because we aimed to identify placebo responders in neurobiological studies. However, we are aware that there is some debate about the reliability and consistency of placebo response 33.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data

Shinohara

Tanaka

Noma

et al. 2019

Evid Based Mental Health

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BackgroundIdentifying potential placebo responders among apparent drug responders is critical to dissect drug-specific and nonspecific effects in depression.ObjectiveThis project aimed to develop and test a prediction model for the probability of responding to placebo in antidepressant trials. Such a model will allow us to estimate the probability of placebo response among drug responders in antidepressants trials.MethodsWe identified all placebo-controlled, double-blind randomised controlled trials (RCTs) of second generation antidepressants for major depressive disorder conducted in Japan and requested their individual patient data (IPD) to pharmaceutical companies. We obtained IPD (n=1493) from four phase II/III RCTs comparing mirtazapine, escitalopram, duloxetine, paroxetine and placebo. Out of 1493 participants in the four clinical trials, 440 participants allocated to placebo were included in the analyses. Our primary outcome was response, defined as 50% or greater reduction on Hamilton Rating Scale for Depression at study endpoint. We used multivariable logistic regression to develop a prediction model. All available candidate of predictor variables were tested through a backward variable selection and covariates were selected for the prediction model. The performance of the model was assessed by using Hosmer-Lemeshow test for calibration and the area under the ROC curve for discrimination.FindingsPlacebo response rates differed between 31% and 59% (grand average: 43%) among four trials. Four variables were selected from all candidate variables and included in the final model: age at onset, age at baseline, bodily symptoms, and study-level difference. The final model performed satisfactorily in terms of calibration (Hosmer-Lemeshow p=0.92) and discrimination (the area under the ROC curve (AUC): 0.70).ConclusionsOur model is expected to help researchers discriminate individuals who are more likely to respond to placebo from those who are less likely so.Clinical implicationsA larger sample and more precise individual participant information should be collected for better performance. Examination of external validity in independent datasets is warranted.Trial registration numberCRD42017055912.

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“…Future designs that represent alternatives to the classical placebo-controlled randomized trial design can be considered. 32 Adopting new methods for the statistical analysis of placebo and treatment effects to be implemented after the data have been collected may also control for placebo effects. 32…”

Section: Issues Related To Biasmentioning

confidence: 99%

Yoga for Substance Use Disorder in Women: A Systematic Review

Brooks

Lawlor

Turetzkin

et al. 2020

International Journal of Yoga Therapy

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It has been suggested that yoga may be an effective adjunct intervention in the management of substance use disorders (SUD). Additionally, women with SUD require different treatment approaches than men. The objective of this study was to critically evaluate the evidence for the effectiveness of yoga, specifically for women, as part of treatment for SUD. Nine electronic databases were searched from inception to January 2020. Randomized controlled trials (RCT) that evaluated any type of yoga, including yoga as a component of mindfulness-based treatment, against any type of control in individuals with any type of addiction were eligible. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist and Statement, methodological quality was appraised using Physiotherapy Evidence Database (PE Dro) criteria. Ten RC Ts (eight mixed-gender and two female-focused) met the eligibility criteria. Most of these RCTs were small to medium-sized, with various methodological and analytical flaws and deficits. The types of addictions included in these studies were alcohol, drug, and nicotine addiction. Most RCTs suggested that various types of yoga, primarily Hatha Yoga and its components, led to favorable or equivalent results for SUD as an adjunct to control or treatment-as-usual interventions. There are limited results on the impact of yoga for SUD specifically focused on women and their unique needs. Although the results of mixed-gender articles are encouraging, large RCTs with gender-specific subanalyses are required to better determine the benefits specific to women incorporating yoga for SUD.

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Methods for assessing and controlling placebo effects

Cited by 13 publications

References 81 publications

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data

Yoga for Substance Use Disorder in Women: A Systematic Review

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