Core Outcome Measures in Effectiveness Trials
www.comet-initiative.org
Acknowledgements
• COMET Management Group:
Doug Altman, Jane Blazeby, Mike Clarke, Paula
Williamson
• COMET project coordinator: Elizabeth Gargon
• Funding: MRC, FP7
• Collaborators: Peter Tugwell, Maarten Boers, Caroline
Terwee, Holger Schunemann, Michael Rose, Sunita
Vohra, Roberto D’Amico, Lorenzo Moja
Health care research is untidy
• It needs to be tidied up if it is to achieve its
aim of helping practitioners and patients to
improve health care and health
• This needs initiatives such as The Cochrane
Collaboration for the preparation and
maintenance of systematic reviews and
COMET for core outcome sets
Systematic review of evidence on
selective outcome reporting
• Studies reporting positive or significant results
are more likely to be published
• Outcomes that are statistically significant are
more likely to be fully reported
• 40–62% of publications had at least one
primary outcome changed, newly introduced
or omitted compared to protocol
[Dwan et al, PLoS ONE 2008]
4
Interviews with trialists (n=59)
• Discussion of outcomes listed in their protocol
but not their trial report
• 29% trials displayed outcome reporting bias
• All trialists mentioned either
- outcomes not measured
- outcomes measured but not analysed
- Lack of clarity about importance or feasibility
of measurement for outcomes chosen
[Smyth et al, BMJ 2010]
5
Core outcome set
• An agreed standardised set of
outcomes that should be
measured and reported, as a
minimum, in all clinical trials in
specific areas of health or
health care
Core outcome set
• Consider both benefits and harms
• The minimum (other outcomes can be
collected)
• Focus is on trials of effectiveness
• “What” to measure, then “How”
Scope of the COS
• “The specific area of health or healthcare that the COS is to
apply to, in terms of health condition, population and types
of interventions needs to be determined.”
• All stages or severity of a specific health condition or
focussed on a particular disease category
- e.g. in colorectal cancer, a COS might be developed for all
patients or it may focus on patients with metastatic disease
• All treatment types or for a particular intervention
- e.g. in morbid obesity, a COS may be created to use in trials of
all interventions or just bariatric surgery alone
Advantages of core outcome sets
• Increases consistency across trials
• Maximise potential for trial to
contribute to systematic reviews of
these key outcomes
• Much more likely to measure
appropriate outcomes
• Major reduction in selective reporting
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• www.omeract.org
• Trials 2007 8:38
Improvements over time (Kirkham et al, Trials 2013)
Studies reporting
full RA COS (%)
Mean number of
clinical outcomes
100
7.0
80
60
drug studies
6.5
40
20
non-drug studies
6.0
0
0.0
1985
1990
WHO/ILAR
RA COS
1995
EMA
guideline
2000
FDA
guideline
2005
2010
The COMET Initiative
• To raise awareness of current problems with
outcomes in clinical trials
• To encourage COS development and uptake
• To provide resources to allow practitioners to
develop COS, e.g. COMET database
• An international network of trialists, systematic
reviewers, health service users, practitioners,
editors, funders, policy makers, regulators
COMET Initiative
• ‘What’ to measure
• ‘How’ to measure (validity, reliability,
feasibility)
- COSMIN
- PROMIS
- PROQOLID
- TREAT-NMD ROM
Website
Background
COMET Database
• A publically accessible internet-based
resource to collate the knowledge base for
core outcome set development
• To include planned and ongoing work, as well
as published core outcome set development
• 200+ published, 50+ ongoing
Search results
Scope
Identifying existing knowledge
Stakeholder involvement
Consensus methods
Achieving global consensus
Regular review, feedback, updating
Implementation
Clear presentation
Stakeholder involvement
•
•
•
•
•
Health care practitioners
Patients, carers, representatives
Regulators
Industry representatives
Researchers
• Stage of involvement may vary by group
Patient and public involvement
• Impact of involvement
– Rheumatology (OMERACT): fatigue
– Chronic pain (IMMPACT): expansion of
previously proposed core outcome
domains
– Multiple sclerosis: fatigue, continence
– Paediatric asthma
Comparison of studies
SINHA ET AL
REDDELL ET AL
BUSSE ET AL
5-11 years
TOP 6 PARENTS +/- CLINICIANS
ESSENTIAL
Symptoms
√
√
Exacerbations
√
√
QoL
√
√
Death
√
Normal activities
√
Exercise ability
√
OPTIONAL
ESSENTIAL
12+ years
OPTIONAL
ESSENTIAL
√
√
√
√
√
√
√
Reliever use
√
Lung function
√
Tx side effects
√
OPTIONAL
√
Healthcare utilisation
√
Biomarkers
√
Hyper-responsiveness
√
√
√
√
√
Professor Hywel Williams, Chair of the NIHR HTA
Commissioning Board: ‘Patients and professionals
making decisions about health care need access to
reliable evidence. The new COMET database will help
researchers across the NIHR family and beyond when
choosing the outcomes to include in the studies that will
establish this evidence base'.
Impact
• Since the COMET website and database were launched in
August 2011:
– 3800+ searches have been undertaken
– 12000+ individuals visited
– 110+ countries visiting the site
www.comet-initiative.org
e.gargon@liv.ac.uk
Twitter: @COMETinitiative