Evidence map›Paper›PMID 34311793›Full record

SynthesisTrials2021

Placebo response and effect in randomized clinical trials: meta-research with focus on contextual effects.

Sigurlaug H Hafliðadóttir, Carsten B Juhl, Sabrina M Nielsen, Marius Henriksen, Ian A Harris, Henning Bliddal, Robin Christensen

Registry-linked trialAbstract readMeta-AnalysisReview
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Trials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06453408 (Validation of a Placebo Dry Needling Protocol in Patients With Non-specific Neck Pain), which is not on this map. Cited by 74 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06453408 naunknown statusnot on this mapstarted 2024, after this paper: background citation

Validation of a Placebo Dry Needling Protocol in Patients With Non-specific Neck Pain: a Randomised Controlled Clinical Trial

TypeinterventionalSponsorUniversity of AlcalaRan2024 to 2024Enrolled70ConditionsNeck PainArmsPunción seca con aguja retráctil, Punción seca con aguja normativa.
3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 8 syntheses or guidelines pooled it.

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  10. Qihuang Needle Therapy for Motor Symptoms in Parkinson's Disease: A Randomized Controlled Trial.Movement disorders : official journal of the Movement Disorder Society · 2026
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  18. Sex assigned at birth may modify health-related quality of life in children treated with peanut oral immunotherapy.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Sigurlaug H HafliðadóttirSection for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Copenhagen F, Denmark.ORCID http://orcid.org/0000-0002-7570-565X
Carsten B JuhlSEARCH Research Group, Research Unit of Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Sabrina M NielsenSection for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Copenhagen F, Denmark.
Marius HenriksenThe Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Ian A HarrisWhitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia.
Henning BliddalThe Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Robin ChristensenSection for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000, Copenhagen F, Denmark. Robin.Christensen@regionh.dk.

Funding

Oak Foundation OCAY-18-774-OFIL
6 · The paper itself

Abstract

backgroundContextual effects (i.e., placebo response) refer to all health changes resulting from administering an apparently inactive treatment. In a randomized clinical trial (RCT), the overall treatment effect (i.e., the post-treatment effect in the intervention group) can be regarded as the true effect of the intervention plus the impact of contextual effects. This meta-research was conducted to examine the average proportion of the overall treatment effect attributable to contextual effects in RCTs across clinical conditions and treatments and explore whether it varies with trial contextual factors.

methodsData was extracted from trials included in the main meta-analysis from the latest update of the Cochrane review on "Placebo interventions for all clinical conditions" (searched from 1966 to March 2008). Only RCTs reported in English having an experimental intervention group, a placebo comparator group, and a no-treatment control group were eligible.

resultsIn total, 186 trials (16,655 patients) were included. On average, 54% (0.54, 95%CI 0.46 to 0.64) of the overall treatment effect was attributable to contextual effects. The contextual effects were higher for trials with blinded outcome assessor and concealed allocation. The contextual effects appeared to increase proportional to the placebo effect, lower mean age, and proportion of females.

conclusionApproximately half of the overall treatment effect in RCTs seems attributable to contextual effects rather than to the specific effect of treatments. As the study did not include all important contextual factors (e.g., patient-provider interaction), the true proportion of contextual effects could differ from the study's results. However, contextual effects should be considered when assessing treatment effects in clinical practice.

trial registrationPROSPERO CRD42019130257 . Registered on April 19, 2019.

Indexed as

Placebo EffectFemaleHumansRandomized Controlled Trials as TopicContextual effectsPlacebo effectPlacebo responseProportional contextual effect

Identifiers

PMID34311793
PMCPMC8314506

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.