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JAMA Article
Calls For Overhaul Of Clinical Trials To Improve Patient Safety
DURHAM, N.C. -- The current system for protecting people
participating in clinical drug trials is outdated and needs to be overhauled,
according to an article in Wednesday's issue of the Journal of the American
Medical Association (JAMA).
"Serious concerns have been raised regarding the processes by which
the safety of participants in clinical trials is currently monitored,"
wrote senior author Dr. Jeremy Sugarman, director of the Center for the Study
of Medical Ethics and Humanities at the Duke University Medical Center. "All
the players in the system recognize that patient safety is a critical issue
that must be addressed."
While no one knows exactly how many people are harmed from adverse events
during clinical trials, Sugarman and Duke co-authors Drs. Michael Morse and
Robert Califf said additional steps need to be taken to further safeguard
clinical trial participants. Clinical trials are tests in which limited
numbers of people use new or experimental medications and medical devices to
ascertain their safety and efficacy. Only after the medications and devices
are tested can they obtain approval from the federal Food and Drug
Administration for broad-based use.
First and foremost, the authors suggest, a formal method of monitoring
must be a part of every clinical trial to review and assess adverse events
during trials. In large trials that may take place at many locations, data
monitoring committees can perform this task. More importantly, they said
information obtained by monitoring committees must be rapidly communicated to
institutional review boards (IRBs). In addition, there needs to be a way to
help IRBs understand whether an adverse event is caused by a problem from the
drug under study or was brought about by a natural course of the disease for
which the patient is being treated. Institutional review boards have long
been the standard for reviewing and approving a study before it begins and
then monitoring its progress to ensure patient safety.
"People in clinical trials are generally sick or are already being
treated for a disease. The experts on a data monitoring committee must be
able to quickly discern between natural occurrences or actual effects of the
disease and what is a truly harmful effect of a study drug," Sugarman
said.
Data monitoring committees recently have been required in all federally
funded late-phase studies. Traditionally, they report each individual adverse
event occurring in a clinical trial, but this practice has made it difficult
for IRBs to accurately evaluate the events, particularly when the trial is
being conducted at multiple sites throughout the country and, even more so,
when studies involve international study sites.
"Moreover, IRBs have become inundated with AERs (adverse event
reports) with as many as several hundred reports submitted to IRBs. Some of
the excessive burden that AERs create for IRBs may be attributed to confusing
terminology in the regulations that govern trials, differing requirements of
the governmental regulatory bodies involved in ensuring patient-subject
safety and inconsistencies in the regulations themselves," Sugarman
said.
In certain cases it is not clear precisely what adverse event reports must
be reported, how rapidly they must be reported, who shoulders the main
responsibility for reporting or to whom completed reports must be submitted,
the authors said. Flooded by adverse event reports and poorly positioned to
interpret the emerging trial data, IRBs have tended to focus on optimizing
regulatory compliance instead of using adverse event reports to determine whether
the risk-benefit assessment for locally enrolled patients is affected.
Federal regulations lack provisions about how IRBs should handle these
reports once they have been received.
"Simply put, communication between all parties involved in clinical
trials must be improved," Sugarman said. "Communication must be
better between the IRBs, the data monitoring committees and the sponsors of
studies. The information must be condensed and better compiled for enhanced
communication. Furthermore, sponsors such as pharmaceutical companies often
do not disclose to researchers data on the true meaning of adverse
events."
Trials sponsors often possess considerable information from other studies
about adverse events, the authors said. They said sponsors should compile and
maintain up-to-date information with cumulative summary of adverse events so
that IRBs can decide on an ongoing basis whether additional safeguards are
required.
The authors also said that safety parameters should be established at the
outset of each study. They said data monitoring committees should provide a
simple, understandable report to each IRB at appropriate and regular
intervals indicating that the safety parameters have not been exceeded and
that there are no reasons, based on evolving information concerning the risks
and benefits, that the study should not continue.
Finally, the authors urged preventing sponsors from being the sole monitor
of a trial, thus removing all potential conflicts of interest.
Note: This story has been adapted from a news release
issued by Duke University Medical Center for journalists and other members of
the public. If you wish to quote from any part of this story, please credit
Duke University Medical Center as the original source. You may also wish to include
the following link in any citation:
http://www.sciencedaily.com/releases/2001/03/010308072201.htm
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