Concerns about selective reporting of clinical trial results by
pharmaceutical companies has become so pronounced that the International
Committee of Medical Journal Editors (ICMJE) has taken the very unusual step
of attempting to directly influence trial reporting procedures(1). The
concern arises from the increasing knowledge that pharmaceutical
companies may only publish trials that show their particular drug works and
omit trial results where a drug doesn't work or is no better than
currently available drugs.
Iain Chalmers, editor at the James Lind Library, wrote recently to the
British Medical Journal describing the laudable action of GlaxoWellcome
announcing its decision to register and seek to report all its
randomised clinical trials(2). However, after GlaxoWellcome had become part of
GlaxoSmithKline (GSK) the company sacked one of the leaders of the
"full reporting" initiative and closed the department she headed.
Actions like this, Lind writes, plus the past record of the
pharmaceutical industry, "prompt deep scepticism that the industry will ever
voluntarily implement ethical trial registration and publication
policies..... Biased under-reporting of clinical trials kills patients...."
A much more in-depth investigation of selective reporting of drug
trials was recently published by a team of researchers from the Institute of
Health Sciences in Oxford, the Cochrane Centre and the University of
Toronto(3). This was the first time an investigation like this had been
done.
This team reviewed 102 medical trials and the reports of them published
in 122 separate journal articles.
Disturbingly, the research found that; "..."....incomplete outcome
reporting is common" and that; "the majority of trials had unreported
outcomes". The team concluded that, bad as these findings were, they
almost certainly under reported the true situation. They came to this
conclusion after finding that researchers would only rarely voluntarily
admit that they had withheld trial results from publication - "86% of
survey responders initially denied the existence of unreported outcomes
despite clear evidence to the contrary".
Overall 50% of outcomes investigating whether a drug or medical
procedure actually worked were "incompletely reported". 65% of outcomes
investigating whether a drug or procedure caused harm were also incompletely
reported.
The reviewers concluded that; "The reporting of trial outcomes is not
only frequently incomplete but also biased and inconsistent with
protocols. Published trials, as well as [subsequent] reviews that incorporate
them, may therefore be unreliable and overestimate the benefits of an
intervention." "... reporting of trial outcomes... is frequently
inadequate to provide sufficient data for interpretation and meta-analysis,
is biased to favour statistical significance, and is inconsistent with
primary outcomes specified in trial procedure. These deficiencies in
outcomes pose a threat to the reliability of the randomised trial
literature."
To try an begin to restore trust in and the reliability of research
reports the ICMJE proposes;
"The International Committee of Medical Journal Editors (ICMJE) will
require, as a condition of consideration for publication [of medical
studies in their journals], registration in a public trials registry...."
"Honest reporting begins with revealing the existence of all clinical
studies, even those that reflect unfavorably on a research sponsor's
product...."
"Trials must register at or before the onset of patient enrollment.
This policy applies to any clinical trial starting enrollment after July
1, 2005. For trials that began enrollment before this date, the ICMJE
member journals will require registration by September 13, 2005, before
considering the trial for publication...."
"Irrespective of their scientific interest, trial results that place
financial interests at risk are particularly likely to remain unpublished
and hidden from public view."
"The case against selective reporting is particularly compelling for
research that tests interventions that could enter mainstream clinical
practice...... We are far from this ideal at present, since trial
registration is largely voluntary, registry data sets and public access to
them varies, and registries contain only a small proportion of trials.
To our knowledge, at present, only www.clinicaltrials.gov, sponsored by
the United States National Library of Medicine, meets [our proposed]
requirements; there may be other registries, now or in the future, that
meet all these requirements.
Research sponsors may argue that public registration of clinical trials
will result in unnecessary bureaucratic delays and destroy their
competitive edge by allowing competitors full access to their research plans.
We argue that enhanced public confidence in the research enterprise
will compensate for the costs of full disclosure. Patients who volunteer
to participate in clinical trials deserve to know that their
contribution to improving human health will be available to inform health care
decisions. The knowledge made possible by their collective altruism must
be accessible to everyone. Trial registration will advance this goal."
Reference: 1. C De Angelis and others. Clinical Trial Registration: A
Statement from the International Committee of Medical Journal Editors
(Editorial). The New England Journal of Medicine. September 8, 2004.
2. "Government regulation is needed to prevent biased under-reporting
of clinical trials" Chalmers I., BMJ 2004;329:462 (21 August)
3. "Empirical Evidence for Selective Reporting of Outcomes in
Randomized Trials", Chan AW., et al., JAMA, May 26, 2004 - Vol 291, No 20 pp
2457-2465.
The ICMJE comprises the editors of; JAMA, New England Journal of
Medicine, The New Zealand Medical Journal, Norwegian Medical Journal, CMAJ,
The Lancet, MEDLINE at the National Library of Medicine, Annals of
Internal Medicine, Croatian Medical Journal, Nederlands Tijdschrift voor
Geneeskunde (Dutch Journal of Medicine), Journal of the Danish Medical
Association, Annals of Internal Medicine and The Medical Journal of
Australia.
