Evidence map›Paper›PMID 24881045›Full record

SynthesisInternational journal of epidemiology2014

Bias due to lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to blind and nonblind sub-studies.

Asbjørn Hróbjartsson, Frida Emanuelsson, Ann Sofia Skou Thomsen, Jørgen Hilden, Stig Brorson

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in International journal of epidemiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 61 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed, 61 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.

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

203 citing papers in PubMed, 61 syntheses or guidelines pooled it.

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  12. Microwave coagulation for liver metastases.The Cochrane database of systematic reviews · 2024
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  16. Motivational interviewing for substance use reduction.The Cochrane database of systematic reviews · 2023
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143 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

5 authors.

Asbjørn HróbjartssonNordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark, Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark and Department of Orthopaedic Surgery, Herlev University Hospital, Herlev, Denmark ah@cochrane.dk.
Frida EmanuelssonNordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark, Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark and Department of Orthopaedic Surgery, Herlev University Hospital, Herlev, Denmark.
Ann Sofia Skou ThomsenNordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark, Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark and Department of Orthopaedic Surgery, Herlev University Hospital, Herlev, Denmark.
Jørgen HildenNordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark, Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark and Department of Orthopaedic Surgery, Herlev University Hospital, Herlev, Denmark.
Stig BrorsonNordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark, Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark and Department of Orthopaedic Surgery, Herlev University Hospital, Herlev, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBlinding patients in clinical trials is a key methodological procedure, but the expected degree of bias due to nonblinded patients on estimated treatment effects is unknown.

methodsSystematic review of randomized clinical trials with one sub-study (i.e. experimental vs control) involving blinded patients and another, otherwise identical, sub-study involving nonblinded patients. Within each trial, we compared the difference in effect sizes (i.e. standardized mean differences) between the sub-studies. A difference <0 indicates that nonblinded patients generated a more optimistic effect estimate. We pooled the differences with random-effects inverse variance meta-analysis, and explored reasons for heterogeneity.

resultsOur main analysis included 12 trials (3869 patients). The average difference in effect size for patient-reported outcomes was -0.56 (95% confidence interval -0.71 to -0.41), (I(2)=60%, P=0.004), i.e. nonblinded patients exaggerated the effect size by an average of 0.56 standard deviation, but with considerable variation. Two of the 12 trials also used observer-reported outcomes, showing no indication of exaggerated effects due lack of patient blinding. There was a larger effect size difference in 10 acupuncture trials [-0.63 (-0.77 to -0.49)], than in the two non-acupuncture trials [-0.17 (-0.41 to 0.07)]. Lack of patient blinding also increased attrition and use of co-interventions: ratio of control group attrition risk 1.79 (1.18 to 2.70), and ratio of control group co-intervention risk 1.55 (0.99 to 2.43).

conclusionsThis study provides empirical evidence of pronounced bias due to lack of patient blinding in complementary/alternative randomized clinical trials with patient-reported outcomes.

Indexed as

BiasDouble-Blind MethodRandomized Controlled Trials as TopicSingle-Blind MethodHumansBiasblindingpatient blindingrandomized clinical trialssystematic review

Identifiers

PMID24881045
PMCPMC4258786

What OpenQuestion holds

Textmetadata
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.