Amanda Burton and
I am a results information research
specialist at clinicaltrials.gov.
This presentation will describe
the history of the clinical trial,
transparency and disclosure landscape.
The first part in this micro
learning of the overview of the
clinical trial disclosure landscape.
During this presentation I
will cover 4 main topics.
First I will discuss the public benefits
of access to clinical trial information.
Next I would describe three key
publication issues and the
impact of these issues within the
transparency and disclosure landscape.
Finally, we will discuss some
key clinical trial reporting
requirements that have been enacted
in order to address this impact.
The transparency of clinical
trial information is vital
in increasing public trust in
and advancing clinical research.
There are many public benefits of
access to clinical trial information.
Primarily transparent reporting of
clinical trials meets an ethical
obligation to human subjects.
The registration of trials enhances
patient access to enrollment
in clinical trials,
while the reporting of clinical trial
results can inform future research
and research funding decisions and
mitigate the potential for information
bias that can stem from non publication
or alteration of trial results.
Access to clinical trial information
also allows the research community to
evaluate adherence to the pre-specified
study protocol and by extension,
the integrity of the research to
prevent duplication of trials of
unsafe or ineffective interventions
and to provide access to data to
support evidence based medicine.
Each of these benefits of transparency
contributes to increase public
trust in clinical research.
There have been important issues impacting
the transparency and disclosure landscape,
however, that have led to the development of
key clinical trial reporting requirements
to address the impact of these issues.
Next I will discuss some key issues
and relying on publications alone to
convey the results of clinical trials
in the impact of these issues in the
clinical trial disclosure landscape.
The first key publication issue
is that not all clinical trials
are published in the literature.
Studies that failed to produce
significant results or are terminated
due to safety concerns can be
unknown to other researchers in.
This could potentially result
in the duplication of efforts,
expend valuable funding and
resources on unproductive efforts,
and bias interpretation of
existing results in the literature.
One prominent article in the New England
Journal of Medicine by Turner and
colleagues highlights comparisons made
between published outcomes and reviews
from the Food and Drug Administration.
The FDA on the same or matched
outcomes in industry trials.
Looking at the effectiveness
of anti-depressants.
This figure shows the authors
found that the majority of study
is viewed by the FDA as having
positive results were published.
But studies viewed by the FDA is having
negative or questionable results were
largely not published or published
in a way that in the author's
opinions conveyed a positive outcome.
Largely biasing the literature
towards positive results of
these treatments being effective.
Another article from the British
Medical Journal indicates that the
issue of not all clinical trials
being published in the literature.
Has also been the case for NIH
federally funded clinical trials.
This study found that fewer than half
of NIH funded trials registered on
clinicaltrials.gov after September of
2005 and completed by December of 2008,
were published in a peer reviewed
biomedical journal indexed by Medline
within 30 months of trial completion.
And after a median of 51 months
after study completion,
1/3 of NIH funded trials in the
sample remained unpublished.
The next key issue is that publications
do not always include prespecified outcome
measures assessed during the clinical trial.
Leading to discrepancies in
what may be reported elsewhere,
such as the ClinicalTrials.gov database.
In a study done by Hartung and colleagues
they found from a random sample of 110
phase three or phase four trials with
results in the clinicaltrials.gov database.
That 8% of the trials had inconsistent
numbers of primary outcome measures,
and 80% of the trials had inconsistent
numbers of secondary outcome measures
reported in the database versus what
was reported in the match publication.
Our discrepancies such as this
appear to be common.
This can make it difficult to know
which source has the most accurate
account of results and points to
the larger issue of not relying on
the publication alone as the only
source of clinical trial information.
Finally,
another key issue is that publications
may contain unacknowledged changes
made from the trial protocol.
For example, changes to the prespecified
outcome measures that can affect
the interpretation of the findings.
One important case from the trial literature
is the analysis of the class study.
Looking at the effects of Cox
two inhibitors such as celecoxib or Celebrex
versus non steroidal anti inflammatory
drugs on gastrointestinal complications
in the treatment of arthritis conditions.
The publication for this trial concluded
that the drug under study celecoxib or
Cox two inhibitor was associated with
a lower incidence of complications
compared with traditional non
steroidal anti inflammatory drugs.
However, it was found that complete
information available from the FDA
showed that the publication was actually
reporting a combined analysis of the
first six months of two separate longer
trials deviating from the prespecified
outcome of a 12 month analysis.
The results at six months showed a
significant reduction in the percentage of
ulcer complications while on celecoxib.
Compared to traditional non
steroid anti inflammatory drugs.
However,
the originally specified analysis
of the 12 month data
showed that over time there was
no difference between treatments.
The change in the pre specified 12
month analysis to show the significant
results at the six month time point in
the publication highlights the important
issue of relying only on the publication,
the generate conclusions or
interpretations of the results.
These issues show that because of
incomplete or inconsistent disclosure,
of results.
For example,
in publications that this can
impede the scientific process.
Further,
the implications for incomplete
reporting and subsequent lack of
availability of clinical trial
data is particularly problematic.
Clinical trials depend on human volunteers,
and it is important to acknowledge their
time and effort and to encourage future
participation from patient populations.
The results of trials,
whether significant or not,
can inform whether future research
opportunities should be pursued.
and informed medical decisions.
In summary,
the impact of these historical issues
across the clinical trial disclosure
landscape have led to the development of
key clinical trial reporting requirements,
such as by the International
Committee of Medical Journal Editors,
the ICMJE,
and the federal government.
This table breaks down key
reporting requirements by policy
and when they became effective,
what the policy requires and the scope, phase,
and intervention type under that policy.
In addition,
there are other selected reporting
requirements located on the resources
page where you access this video.
Thank you for your attention
to this presentation.
For additional resources related to
the history of the clinical trial,
transparency and disclosure landscape,
please review the page from
which you accessed this video.