Still couldn't get the link to work. Perhaps the text copy will do.
The
new england journal
of
medicine
n engl j med
352;23
www.nejm.org june
9, 2005
2436
editorials
Is This Clinical Trial Fully Registered? — A Statement
from the International Committee of Medical Journal Editors
In September 2004, the members of the International
Committee of Medical Journal Editors (ICMJE)
published a joint editorial aimed at promoting registration
of all clinical trials.
1
We stated that we will
consider a trial for publication only if it has been
registered before the enrollment of the first patient.
This policy applies to trials that start recruiting on
or after July 1, 2005. Because many ongoing trials
were not registered at inception, we will consider
for publication ongoing trials that are registered
before September 13, 2005. Our goal then and now
is to foster a comprehensive, publicly available database
of clinical trials. A complete registry of trials
would be a fitting way to thank the thousands of participants
who have placed themselves at risk by volunteering
for clinical trials. They deserve to know
that the information that accrues from their altruism
is part of the public record, where it is available
to guide decisions about patient care, and deserve to
know that decisions about their care rest on all of
the evidence, not just the trials that authors decided
to report and that journal editors decided to publish.
We are not alone in pursuing this goal. The
World Health Organization (WHO), through meetings
in New York, Mexico City, and Geneva, has
brought us close to the goal of a single worldwide
standard for the information that trial authors must
disclose. Around the world, governments are beginning
to legislate mandatory disclosure of all trials.
For example, among the bodies considering new
legislation is the U.S. Congress, where the proposed
Fair Access to Clinical Trials (FACT) Act would expand
the current mandate for registration of clinical
trials. Many other journals have adopted our policy
of requiring trial registration. These initiatives
show that trial registration has become a public issue.
But, as our deadline for registration approaches,
trial authors and sponsors want to be sure that
they understand our requirements, so that reports
of their research will be eligible for editorial review.
The purpose of this joint and simultaneously published
editorial is to answer questions about the
ICMJE initiative and to bring our position into harmony
with that of others who are working toward
the same end.
Our definition of a clinical trial remains essentially
the same as in our September 2004 editorial:
“Any research project that prospectively assigns
human subjects to intervention and comparison
groups to study the cause-and-effect relationship
between a medical intervention and a health outcome.”
By “medical intervention” we mean any intervention
used to modify a health outcome. This
definition includes drugs, surgical procedures, devices,
behavioral treatments, process-of-care changes,
and the like. We update our 2004 editorial to state
that a trial must have at least one prospectively assigned
concurrent
control or comparison group in order
to trigger the requirement for registration.
Among the trials that meet this definition, which
need to be registered? The ICMJE wants to ensure
public access to all “clinically directive” trials — trials
that test a clinical hypothesis about health outcomes
(e.g., “Is drug X as effective as drug Y in treating
heart failure?”). We have excluded trials from
our registration requirement if their primary goal
is to assess major unknown toxicity or determine
pharmacokinetics (phase 1 trials). In contrast, we
think the public deserves to know about trials that
could shape the body of evidence about clinical effectiveness
or adverse effects. Therefore, we require
registration of all trials whose primary purpose is
to affect clinical practice (phase 3 trials). Between
these two extremes are some clinical trials whose
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n engl j med
352;23
www.nejm.org june
9, 2005
editorials
2437
prespecified goal is to investigate the biology of disease
or to provide preliminary data that may lead to
larger, clinically directive trials.
We recognize that requiring public registration
of trials whose prespecified goal is to investigate the
biology of disease or to direct further research might
slow the forces that drive innovation. Therefore,
each journal editor will decide on a case-by-case basis
about reviewing unregistered trials in this category.
Authors whose trial is unregistered will have
to convince the editor that they had a sound rationale
when they decided not to register their trial. The
ICMJE will maintain this policy for the next two
years. We will then review our experience.
Our September 2004 editorial specified the information
that we would require for trial registration.
Attendees at a recent meeting of the WHO
registration advisory group identified a minimal
* The data fields were specified at a meeting convened by the WHO in April 2004; the explanatory comments are largely
from the ICMJE.
Table 1. Minimal Registration Data Set.*
Item Comment
1. Unique trial number The unique trial number will be established be the primary registering entity
(the registry).
2. Trial registration date The date of registration will be established by the primary registering entity.
3. Secondary IDs May be assigned by sponsors or other interested parties (there may be none).
4. Funding source(s) Name of the organization(s) that provided funding for the study.
5. Primary sponsor The main entity responsible for performing the research.
6. Secondary sponsor(s) The secondary entities, if any, responsible for performing the research.
7. Responsible contact person Public contact person for the trial, for patients interested in participating.
8. Research contact person Person to contact for scientific inquiries about the trial.
9. Title of the study Brief title chosen by the research group (can be omitted if the researchers wish).
10. Official scientific title
of the study
This title must include the name of the intervention, the condition being studied,
and the outcome (e.g., The International Study of Digoxin and Death from
Congestive Heart Failure).
11. Research ethics review Has the study at the time of registration received appropriate ethics committee approval
(yes/no)? (It is assumed that all registered trials will be approved by an
ethics board before commencing.)
12. Condition The medical condition being studied (e.g., asthma, myocardial infarction,
depression).
13. Intervention(s) A description of the study and comparison/control intervention(s). (For a drug or
other product registered for public sale anywhere in the world, this is the generic
name; for an unregistered drug the generic name or company serial number is
acceptable). The duration of the intervention(s) must be specified.
14. Key inclusion and exclusion
criteria
Key patient characteristics that determine eligibility for participation in the study.
15. Study type Database should provide drop-down lists for selection. This would include choices
for randomized vs. non-randomized, type of masking (e.g., double-blind, singleblind),
type of controls (e.g., placebo, active), and group assignment (e.g., parallel,
crossover, factorial).
16. Anticipated trial start date Estimated enrollment date of the first participant.
17. Target sample size The total number of subjects the investigators plan to enroll before closing the trial
to new participants.
18. Recruitment status Is this information available (yes/no)? (If yes, link to information.)
19. Primary outcome The primary outcome that the study was designed to evaluate. Description should
include the time at which the outcome is measured (e.g., blood pressure at
12 months).
20. Key secondary outcomes The secondary outcomes specified in the protocol. Description should include time
of measurement (e.g., creatinine clearance at 6 months).
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new england journal
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n engl j med
352;23
www.nejm.org june
9, 2005
registration data set of 20 items (Table 1). The
WHO-mandated items collectively address every key
requirement that we established in our September
2004 editorial. The ICMJE supports the WHO minimal
data set and has adopted it as the ICMJE’s requirement:
we will consider a trial for publication
if the authors register it at inception by completing
all 20 fields in the WHO minimal data set. As individual
editors, we will review the data in the registration
fields when we decide whether to consider
the trial for publication. We will consider a registration
data set inadequate if it has missing fields or
fields that contain uninformative terminology. If
an investigator has already registered a clinical trial
in a publicly owned, publicly accessible registry
using the data fields that we specified in our 2004
editorial, we will consider that registration to be
complete as long as each field contains useful information.
Acceptable completion of data fields is an important
concern. It shouldn’t be, but it is. Many entries
in the publicly accessible clinicaltrials.gov database
do not provide meaningful information in
some key data fields. A search conducted on May 4,
2005 (Zarin D.: personal communication) indicates
that certain pharmaceutical-company entries list a
meaningless phrase (e.g., “investigational drug”)
in place of the actual name of the drug, even though
a U.S. law requires trial registrants to provide
“intervention name” (
www.fda.gov/cder/guidance/
4856fnl.htm). Many companies and other entities
are completing the data fields in a meaningful fashion.
Data entries must include information that
will be of value to patients and health professionals;
the intervention name is needed if one is to
search on that intervention.
We recognize that clinical trial registries have
many uses, but whatever the use, a worldwide uniform
standard for a minimal database is necessary.
We have participated in the WHO effort to establish
a clinically meaningful trial registration process.
The ICMJE supports this ongoing project. When it
is complete we will evaluate the process, and if it
meets our primary objectives, we will adopt it.
We stated our requirements for an acceptable
trial registry in the September 2004 editorial, and
they remain the same. The registry must be electronically
searchable and accessible to the public at no
charge. It must be open to all registrants and not for
profit. It must have a mechanism to ensure the validity
of the registration data.
The purpose of a clinical trials registry is to promote
the public good by ensuring that everyone can
find key information about every clinical trial whose
principal aim is to shape medical decision-making.
We will do what we can to help reach this goal. We
urge all parties to register new and ongoing clinical
trials. If in doubt about whether a trial is “clinically
directive,” register it. Don’t use meaningless phrases
to describe key information. Every trial participant
and every investigator should be asking, “Is
this clinical trial fully registered?”
1.
De Angelis C, Drazen JM, Frizelle FA, et al. Clinical trial registration:
a statement from the International Committee of Medical Journal
Editors. N Engl J Med 2004;351:1250-1.
Catherine D. De Angelis, M.D., M.P.H.
Editor-in-Chief,
JAMA
Jeffrey M. Drazen, M.D.
Editor-in-Chief,
New England Journal of Medicine
Prof. Frank A. Frizelle, M.B.,Ch.B., M.Med.Sc.,
F.R.A.C.S.
Editor,
The New Zealand Medical Journal
Charlotte Haug, M.D., Ph.D., M.Sc.
Editor-in-Chief,
Norwegian Medical Journal
John Hoey, M.D.
Editor,
CMAJ
Richard Horton, F.R.C.P.
Editor,
The Lancet
Sheldon Kotzin, M.L.S.
Executive Editor, MEDLINE
National Library of Medicine
Christine Laine, M.D., M.P.H.
Senior Deputy Editor,
Annals of Internal Medicine
Ana Marusic, M.D., Ph.D.
Editor,
Croatian Medical Journal
A. John P.M. Overbeke, M.D., Ph.D.
Executive Editor,
Nederlands Tijdschrift voor Geneeskunde
(
Dutch Journal of Medicine
)
Torben V. Schroeder, M.D., D.M.Sc.
Editor,
Journal of the Danish Medical Association
Harold C. Sox, M.D.
Editor,
Annals of Internal Medicine
Martin B. Van Der Weyden, M.D.
Editor,
The Medical Journal of Australia
Copyright © 2005 Massachusetts Medical Society.
Copyright © 2005 Massachusetts Medical Society. All rights reserved.
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