Core outcome sets and trial registries
Clarke and Williamson Trials
Core outcome sets and trial registries
Mike Clarke 0
0 Northern Ireland Network for Trials Methodology Research, Centre for Public Health, Institute of Clinical Sciences , Block B , Queens University Belfast, Royal Hospitals , Grosvenor Road, Belfast BT12 6BJ , UK
Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.
There are many reasons for registering trials. Some of
these might be considered as self-serving, such as
satisfying the requirement that trials be prospectively
registered before the first patient is randomised if the
researchers wish to publish their findings in certain
journals  or publicising the trial to try to boost
recruitment. Registry entries also help others to know
what studies are ongoing and will help future
systematic reviewers to examine the risks to their review of
reporting biases and to see what was planned at the
start of a trial. Trial registration contributes to reducing
waste in research by helping to avoid unnecessary
duplication of effort  and making it easier for health
and social care research to be cumulative . It is also
an opportunity to focus the attention of the researchers
on ensuring that their trial is designed in a way that will
maximise its potential for impact on future decisions
and policy. To maximise impact, however, it is vital that
the outcomes that will be measured and reported are
carefully chosen and will be relevant to those making
decisions and setting policy in the future. This
commentary highlights how careful consideration of core
outcome sets when registering trials might help with
choosing outcomes and how a trial registry such as
ISRCTN might assist with this.
Some of the advantages of trial registration rely on
clarity in the registry entry, so that the trial design is
clear; furthermore, preparing the entry may be an
opportunity for the researchers to give careful consideration to
each of its elements. Of course, much of this
consideration is likely to have taken place during earlier stages in
the trial such as during the preparation of the trial
protocol, when making submissions for funding, while
seeking ethical approval and when satisfying other
requirements such as research governance. The
researchers should have already considered the scientific,
ethical and environmental justification for the trial.
Ideally, this might have been through a systematic review
of the existing evidence to elucidate the need for the trial
and to demonstrate the uncertainty that it seeks to resolve
. In many areas of health and social care, one of the
things that a systematic review is likely to have made even
clearer to the researchers is the problem caused by
inconsistencies in how earlier research has chosen, measured
and reported outcomes.
The need to standardise outcomes across research in the
Heterogeneity in how trials have been done can bring
richness to systematic reviews and meta-analyses by
testing different forms of an intervention, action or strategy
and by testing these in different settings and with
different populations. However, heterogeneity in the outcomes
can hamper or prevent the ability of reviewers to pool
the findings of studies in meta-analyses [5, 6] and will
impede efforts to streamline the systematic reviewing
process . Inconsistency in outcome measurement
across trials in the same area, a lack of data on
important outcomes from all trials, and selective reporting of
outcomes compound the problems faced by users of
research [8, 9]. One way to reduce this waste is through
the development of agreed upon, standardised sets of
outcomes for research in specific areas of health and
social care. The implementation of these core outcome
sets in all trials in a particular topic area would
maximise the ability of the researchers themselves, reviewers
and others to compare, contrast and combine the
findings of the separate trials. Their use is now encouraged
by funders of research, including the National Institute
for Health Research in the UK .
Core outcome sets
If core outcome sets are to meet their potential to help
researchers ensure that the outcomes they measure and
report are the most relevant to users of their trial, these
outcome sets need to be developed in a collaborative
way with appropriate representation from key
stakeholders. This is likely to include practitioners, patients
and others users of health and social care services, as
well as researchers, research funders, policy makers and
those who pay for health and social care services.
Although sporadic examples of what might now be
considered to be core outcome sets have existed for some time
, and well-established ones, such as OMERACT for
rheumatoid arthritis, appear to have had an impact on
trial design , the use of these sets is still in a period
of relative infancy. Over the last five years, the COMET
Initiative has been seeking to support others in the
development and uptake of core outcome sets across
health and social care  and has shown the wide
variety of methods that have been used to develop them
. Guidance is beginning to appear , and a recent
systematic review identified nearly 200 examples .
Using core outcome sets when registering a trial
These core outcome sets have been brought together in
a unique resource in the COMET database, which is
freely available on the internet (www.cometinitiative.org/
studies/search). This makes it much easier for researchers
to identify a core outcome set if one already exists, as is
evidenced by the fact that more than 25,000 records had
to be checked as part of the systematic review . As
part of the planning for their trial, researchers who wish to
maximise the potential impact of their findings need to
ensure that they will measure outcomes that will make
it easier to show the relevance of those findings. They
can do this by determining whether or not a core
outcome exists, and in some cases, people embarking on a
programme of research have developed a core outcome
set to ensure the relevance of the outcomes they will
measure and report . Researchers should consider a
core outcome set when designing their trial. This does
not restrict the outcomes that they will measure but
does provide them with the minimum outcomes that
they need to include. They remain able to include
additional outcomes, especially those that may be
particularly pertinent to their study.
Then, when it comes to registering a trial, the trial
registry should encourage researchers to note their use
of the core outcome set and to specify each of the
outcomes from the core set, as well as any additional
outcomes, that they will measure. Specifying the outcomes
from the core outcome set and using the terms for these
outcomes that were used in that core outcome set will
facilitate searching by users of the registry. In fact, this
could be made even easier if the registry entry could be
automatically populated with the outcomes through a
dynamic link to the core outcome set cited by the
researchers. Another benefit from considering the core
outcome set in the design and registration of their trial
is that researchers may be helped in their choice of
primary outcomes. These outcomes are likely to be used to
determine the sample size for the trial but also will
highlight the areas on which the researchers will focus. For
example, the primary outcomes will be those on which
they will focus most when seeking to minimise loss to
follow-up and missing data.
When others inspect the registry entry for a closed
trial, the explicit use of a core outcome set will facilitate
one of the other benefits of a prospective registry: the
ability to determine the risk of bias from measured, but
not reported, outcomes. If outcomes from the core
outcome set are not subsequently included in reports of the
trial, this will help reviewers and others to investigate
the potential impact of selective reporting bias on any
decisions they wish to make.
Trial registries can facilitate these efforts to make new
trials as useful as possible and to reduce waste.
Guidelines for reporting protocols for research acknowledge
the potential value of core outcome sets , and an
important next step would be for trial registries to do
likewise. The section in the registry entry for the outcomes
for the trial could prompt the researcher to consider
using a core outcome set, facilitate the specification of
that core outcome set and its component outcomes
through linking to the original core outcome set, and
encourage the choice of one or more primary outcomes
from within the core outcome set. In doing this, trial
registries will contribute to the global effort to ensure
that trials answer important uncertainties and can be
brought together in systematic reviews. We welcome
comments on these suggestions and on how greater use
of core outcome sets in trial registries might help
researchers to achieve their ultimate aim of improving
health and well-being through improving health and
COMET has received funding from the Medical Research Council
Methodology Research Programme (grant number MR/J004847/1) and
European Union Seventh Framework Programme ([FP7/2007-2013] [FP7/
2007-2011]) under grant agreement n 305081.
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