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Guidelines for reporting research

Doug AltmanCentre for Statistics in

Medicine Oxford

NCRI, 24 January 2006

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Biased reporting is scientific misconduct

“Failure to publish an adequate account of a well-designed clinical trial is a form of scientific misconduct which can lead those caring for patients to make inappropriate treatment decisions.”

[Chalmers, 1990]

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Clinical trials

Focus on randomised clinical trials (RCTs)– Principles of good reporting apply to all types of

research

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Outline

Importance of clinical trials Importance of good reporting Evidence of bad reporting Reporting guidelines - CONSORT Publication (dissemination) bias

– Bias from unpublished research– Bias in published research

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Chalmers & Altman. How can medical journals help prevent poor medical research? Some

opportunities presented by electronic publishing. Lancet 1999

Electronic publication of a protocol could be simply the first element in a sequence of “threaded” electronic publications, which continues with reports of the resulting research (published in sufficient detail to meet some of the criticisms of less detailed reports published in print journals), followed by deposition of the complete data set. Not only would this approach allow alternative explorations of the data, it would help to address some of the growing concerns about research misconduct.

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Data for clinical trials

Knowledge of existence (registration) Trial protocol

– Including detailed analysis plan Results of analyses Raw data Other documents

– e.g. Data collection forms

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Importance of good reporting

“The whole of medicine depends on the transparent reporting of

clinical trials”

Rennie D. CONSORT revised—improving the reporting of randomized trials. JAMA

2001;285:2006-7.

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Importance of good reporting

Assessment of quality and relevance of research is seriously impeded by inadequate reporting

Randomised controlled trials (RCTs) should be reported fully and accurately– Existence of trials and main findings, to ensure that we

see all the evidence, not a biased subset– Clear details of what was done, to enable evaluation of

the reliability of findings – Full reporting of all results (outcomes), to contribute to

the overall evidence of interventions (benefits and harms)

Much evidence indicates that all areas are deficient

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Poor reporting of RCTs is common 1

Not reporting an adequate method for generating random numbers – 68% of 206 trials in obstetrics & gynecology journals– 52% of 80 trials in general medical journals

Not reporting the mechanism used to allocate interventions – 89% of 196 trials in rheumatoid arthritis – 48% of 206 trials in obstetrics & gynecology journals– 44% of 80 trials in general medical journals– 93% of 73 trials in one dermatology journal – 96% of 2000 trials in schizophrenia– 99% of 122 trials of SSRIs

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Poor reporting of RCTs is common 2

Not stating whether blinding was used– 51% of 506 trials in cystic fibrosis– 33% of 196 trials in rheumatoid arthritis– 38% of 68 trials in dermatology

Poor reporting of adverse effects of interventions– 61% of 192 reports in 7 medical areas

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The CONSORT statement[Begg et al 1996; Moher et al 2001]

22 items which should be reported in a paper

Also a flow diagram showing patient progress through the trial (to be included in the trial report)

Evidence-based, whenever possible Accompanied by a long explanatory

document

www.consort-statement.org

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ExcludedExcluded

Not meeting inclusion criteriaNot meeting inclusion criteria

Refused to participateRefused to participate

Other reasonOther reason

Assessed Assessed for eligibilityfor eligibility

(n=…)

RandomizedRandomized

Allocated to interventionAllocated to intervention

Received allocated interventionReceived allocated intervention

Did not receive allocatedDid not receive allocated intervention (give reasons) intervention (give reasons)

Lost to follow upLost to follow up

Discontinued intervention Discontinued intervention (give reasons)(give reasons)

AnalysedAnalysed

Excluded from analysisExcluded from analysis

Allocated to interventionAllocated to intervention

Received allocated interventionReceived allocated intervention

Did not receive allocatedDid not receive allocated intervention (give reasons) intervention (give reasons)

Lost to follow upLost to follow up

Discontinued intervention Discontinued intervention (give reasons)(give reasons)

AnalysedAnalysed

Excluded from analysisExcluded from analysis

Anal

ysis

Anal

ysis

Follo

w up

Follo

w up

Allo

catio

nAl

loca

tion

Enro

llmen

tEn

rollm

ent

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CONSORT checklist (22 items)TITLE & ABSTRACTINTRODUCTION BackgroundMETHODS Participants Interventions Objectives Outcomes Sample size Randomization

Sequence allocation Allocation concealment Implementation

Blinding (Masking) Statistical methods

RESULTS Participant flow Recruitment Baseline data Numbers analyzed Outcomes and

Estimation Ancillary analyses Adverse eventsDISCUSSION Interpretation Generalisability Overall evidence

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CONSORT items

There are really >22 items

Item 6:– Clearly defined primary and secondary outcome

measures and, when applicable, any methods used to enhance the quality of measurements (e.g., multiple observations, training of assessors).

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Avoid unhelpful labels

CONSORT does not use term “double blind”

Item 11:– Whether or not participants, those administering

the interventions, and those assessing the outcomes were blinded to group assignment.

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Secondary goal of CONSORT

“To encourage and provide incentives for researchers to conduct high-quality, unbiased randomized trials”– Arguably even more important

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Extensions

Cluster RCTs (BMJ 2004) Harms (Ann Intern Med 2004) Noninferiority RCTs (JAMA 2006)

More planned

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Factors in success of CONSORT

Membership of Group– Methodologists– Trialists– Editors

Reporting rather than conduct Focus on main issues

– ‘One side of paper’ No competitors High profile publications Supported by Editorial groups, >150

journals, peer review granting agencies

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Process 1

Preparation– Assessment of existing literature on reporting– Identification of relevant empirical evidence

Meeting of experts– Clear scope– Clear aim – reporting not conduct– Develop checklist (& flow diagram)

Small group fine-tunes checklist and develops publications– Seek input from wider group (e.g. on web)

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Process 2

Publications– Statement– Explanatory document

Web site – Extra material– Invite comments– etc

Periodic revision – Take account of feedback / criticism– Take account of new evidence

NB no funding!!

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Some history of reporting guidelines developed by

consensus 1993-94 SORT RCT1994 Asilomar RCT1995-96 CONSORT RCT1996-99 QUOROM SR/M-A of RCTs1997-00 MOOSE M-A of obs studies1999-01 CONSORT II RCT2000-03 STARD Diagnostic2003-04 TREND NonRCT/Behavioural2001-05 REMARK Prognostic (cancer)2004-?? STROBE Observational 2005-?? QUOROM II SR/M-A of RCTs

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Impact of CONSORT

Review of ‘Instructions to Authors’ of 167 high impact medical journals in 2003 – 36/166 (22%) referred to CONSORT

8 published studies show that adoption of CONSORT by journals is associated with improved reporting of RCTs– Much room remains for improvement

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Publication (dissemination) bias

Study not published Only selected findings published Stopping a trial early for benefit

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Outcomes

Publication

Outcomes

From trial to review

Trial 2Trial 1 Trial 3

Systematic review

Publication Publication

Outcomes

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Publication biases

Study publication bias selective publication of entire studies

Outcome reporting bias selective reporting of outcomes within

published studies

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Study publication bias

Studies reported at conferences are less likely to be fully published if not significant– Statistically significant results are about 20% more

likely to be published [Scherer et al, CDMR 2004]

Even when published nonsignificant studies take longer to reach publication that those with significant findings– Trials with null or negative findings took an average

just over a year longer to be published than those with positive results [Hopewell et al, CDMR 2001]

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Full publication bias (abstracts not leading to full

papers)

Cohort of 500 oncology trials with >200 participants [Krzyzanowska et al, JAMA 2003]

Preliminary results presented at ASCO 26% not published in full within 5 years

– 81% with P<0.05 were published– 68% with P>0.05 were published

So not just a problem of small trials!

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3 studies of selective reporting of trial results [Chan et al, 2004

& 2005]

• Study of published reports of RCTs– All Medline-indexed RCTs published in Dec 2000

• 519 RCTs, >10000 outcomes

Comparison of protocols and publications– 102 RCTs submitted to the Copenhagen and

Frederiksberg Research Ethics committee in 1994-95

– 48 RCTs funded by CIHR 1990-98

Questionnaire sent to all authors in each cohort

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Pooled OR for outcome reporting bias (fully versus incompletely reported

outcomes) by study design and cohort

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Impact of these biases

Study publication bias: odds ratio of 2.0– 81% of studies with P<0.05 were published– 68% of studies with P>0.05 were published

Selective reporting: odds ratio of 2.4– 71% of outcomes with P<0.05 are fully reported

– 50% of outcomes with P>0.05 are fully reported

Biases are cumulative– Hard to quantify overall impact

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Major discrepancies in the specification of primary outcomes

between protocols and publications

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Protocols

Clearly, trial protocols need to be in the public domain– Preferably before the trial finishes

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Biased reporting is scientific misconduct

“In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly.”

[“Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors”, September 2004]

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Data for clinical trials

Knowledge of existence (registration) Trial protocol

– Including detailed analysis plan Results of analyses Raw data Other documents

– e.g. Data collection forms

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