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EDITORIAL
Why should clinical trials be registered?
Elizabeth Wager and Nadia Elia
European Journal of Anaesthesiology 2014, 31:397–400
Would you enter a clinical trial if the consent form included
the statement ‘Although clinical trials aim to improve
medical knowledge, only about half ever get published
in medical journals and, of those that are published, around
half the measurements won’t be reported in the article, so
doctors won’t have a chance to read about them’? Or, even
worse: ‘If this trial doesn’t produce results that support the
sponsor’s product (or the investigator’s theory) it probably
won’t be published’. It is hard to imagine any patient
consenting to take part in a trial under these circumstances.
To make matters worse, positive findings may be pub-
lished more than once, and sometimes in ways that delib-
erately obscure the fact that they are duplicates, and this
can further skew the evidence base towards the positive
findings.
1
Nonpublication, selective publication and cov-
ert duplicate publication all contribute to the problem of
publication bias.
2
What is the evidence of publication bias?
Trial registers have been used to measure the problem of
nonpublication. Ross et al.
3
found that only 46% of a
sample of 677 trials (excluding phase I studies) that were
registered on ClinicalTrials.gov, and had completed by
2005, were published by 2007. (If they could not find a
publication on Medline, Ross’s team emailed a trial
official to ask whether the trial had been published; of
the 117 contacted, four provided a publication, 40 con-
firmed that the trial had not been published, and 73 did
not reply). More recently, Jones et al.
4
assessed 585
clinical trials that had recruited at least 500 participants,
were registered on ClinicalTrials.gov and had completed
by January 2009. They found that, by November 2012,
29% of these trials remained unpublished. These studies
show the worrying rate of nonpublication in both regis-
tered and large trials. It is likely that the problem is even
worse among nonregistered and smaller studies.
Yet, until recently, publication bias has received little
attention in the medical literature. One reason for this
may have been the fact that, by its very nature, nonpu-
blication is difficult to investigate, and is hidden from
journal editors. Although peer-review can be used to assess
and improve reports submitted to journals, editors are
powerless about research that is never written up. One
factor that has raised the profile of publication bias is the
growing influence of evidence-based medicine with its
emphasis on systematic reviews and meta-analyses. The
process of assembling and analysing all publications on a
topic may uncover redundant publications and may also
suggest the existence of trials that have remained unpub-
lished.
1
Although editors can do little or nothing about studies that
are not submitted to their journals, they can help to
alleviate the problems of publication bias by supporting
trial registration and by making a commitment to consider
reports of well designed studies regardless of the direction
or statistical significance of their findings. It is, therefore,
good news that the European Journal of Anaesthesiology will
make trial registration a requirement for the publication of
interventional trials. This editorial explains the policy in
more detail and the reasons for its adoption.
What is trial registration?
Registration involves entering details of a trial’s design on
a public database. The WHO has published a 20-item
minimum dataset, which has been adopted by many
registers and used as a criterion for complete registration
by several journals.
5,6
When a trial is accepted onto the
database, it receives a registration number, which can be
quoted on subsequent publications. Some databases
(notably the US register, ClinicalTrials.gov) also enable
a summary of trial results to be posted, but this is a
separate function from the initial registration, which
should, ideally, occur before patients are recruited (and
therefore long before results are available).
Why register trials?
There are several reasons why trials should be registered.
The first reason is that trial registration helps to alleviate
Eur J Anaesthesiol 2014; 31:397–400
From Sideview, Princes Risborough, UK (EW), and Division of Anaesthesiology, University Hospitals of Geneva, Geneva, Switzerland (NE)
Correspondence to Dr Nadia Elia, MD, MSc, Division of Anaesthesiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland
Tel: +41 22 382 74 41; fax: +41 22 382 75 11; e-mail: nadia.elia@hcuge.ch
0265-0215 ß 2014 Copyright European Society of Anaesthesiology DOI:10.1097/EJA.0000000000000084