Evidence map›Paper›PMID 30526685›Full record

ReviewTrials2018

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials.

Jeremy Howick, Rebecca Webster, Nigel Kirby, Kerry Hood

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Trials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 4 pooled it
2.9field-weighted citation impact, top 9% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 4 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

4 authors at 3 institutions in 1 country.

Jeremy HowickNuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care Building, Oxford, OX2 6GG, UK.ORCID http://orcid.org/0000-0003-0280-7206
Rebecca WebsterDepartment of Psychological Medicine, King's College London, 3rd Floor Weston Education Centre, 10 Cutcombe Road, Denmark Hill, London, SE5 9RJ, UK.
Nigel KirbyCentre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 7th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK.
Kerry HoodCentre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 7th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. hoodk1@cardiff.ac.uk.
Cardiff University · GBKing's College London · GBUniversity of Oxford · GB

Funding

Medical Research Council G0800055
6 · The paper itself

Abstract

backgroundTrial participants in placebo groups report experiencing adverse events (AEs). Existing systematic reviews have not been synthesized, leaving questions about why these events occur as well as their prevalence across different conditions unanswered.

objectives(1) To synthesize the evidence of prevalence of AEs in trial placebo groups across different conditions. (2) To compare AEs in trial placebo groups with AEs reported in untreated groups within a subset of randomized trials. SEARCH

methodsWe searched PubMed for records with the word "nocebo" in the title and "systematic" in any field. We also contacted experts and hand-searched references of included studies. STUDY ELIGIBILITY: We included any systematic review of randomized trials where nocebo effects were reported. We excluded systematic reviews of non-randomized studies. PARTICIPANTS AND

interventionsWe included studies in any disease area. STUDY APPRAISAL AND SYNTHESIS

methodsWe appraised the quality of the studies using a shortened version of the Assessment of Multiple Systematic Reviews tool (AMSTAR) tool. We reported medians and interquartile ranges (IQRs) of AEs. Among the trials within the review that included untreated groups, we compared the prevalence of AEs in untreated groups with the prevalence of AEs in placebo groups.

resultsWe identified 20 systematic reviews. These included 1271 randomized trials and 250,726 placebo-treated patients. The median prevalence of AEs in trial placebo groups was 49.1% (IQR 25.7-64.4%). The median rate of dropouts due to AEs was 5% (IQR 2.28-8.4%). Within the 15 of trials that reported AEs in untreated groups, we found that the AE rate in placebo groups (6.51%) was higher than that reported in untreated groups (4.25%). LIMITATIONS: This study was limited by the quality of included reviews and the small number of trials that included untreated groups. CONCLUSIONS AND IMPLICATIONS OF KEY

findingsAEs in trial placebo groups are common and cannot be attributed entirely to natural history. Trial methodologies that reduce AEs in placebo groups while satisfying the requirement of informed consent should be developed and implemented.

Indexed as

Nocebo EffectDrug-Related Side Effects and Adverse ReactionsHumansRandomized Controlled Trials as TopicResearch DesignRisk AssessmentRisk FactorsSystematic Reviews as TopicAdverse eventsNoceboPlaceboRandomized trialSystematic review

Identifiers

PMID30526685
PMCPMC6288933
OpenAlexW2905013711

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.