Testimony
Before the
United States Senate
Health Education Labor and Pensions
Committee
Protecting Human Subjects in Research:
Are Current Safeguards Adequate?
April 23, 2002
Presented by:
Cherlynn Mathias, RN, C
6111 N. Beach
Apt. 1916
Fort Worth, TX 76137
817-820-4954 (w)
817-264-2035 (h)
I am Cherlynn Mathias a Registered Nurse currently working as
the Manager of the Clinical Research Department at Harris Methodist Fort
Worth, a large community hospital in Texas. However, today I am here to
testify about my experiences as a study coordinator at the University of
Oklahoma.
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I was hired in June of 1999 and almost immediately I realized that
ineligible subjects were being enrolled into the Melanoma Clinical Trial
that Dr. J. Michael McGee was conducting. The trial had actually opened
three years before my employment. When I asked about the subjects
being ineligible, I was told that McGee as the Principal Investigator,
(clinical researcher) could enroll whomever he wished and that the
conduct of the study was his responsibility. In late July, Dr. McGee
requested that I build a database, which contained endpoints not described
in his study design. The purpose of the database was to gather statistics
for publication and also for an upcoming medical conference in which
McGee was scheduled to speak. The building of the database required me
to do a retrospective chart review of all the melanoma vaccine patients. In
the course of doing the chart reviews, I discovered that several patients
had been allowed to self inject the vaccine. The patients who were selfinjecting
were storing the vaccine at home in their refrigerators. Not only
was I surprised by this finding because of the obvious concern for drug
accountability record keeping and storage of the experimental drug in an
unsecured environment, but also I was concerned about patient safety.
The Vaccine Protocol called for the drug to be stored at the temperature of
liquid nitrogen. I wondered if the vaccine was stable at the higher
temperatures? Also the patients were at risk for drug reactions that might
be serious and life threatening, such as anaphylactic reactions. It was
obvious that adverse event monitoring was lacking.
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In July after discovering that a monitoring plan had never been
developed, I was able to convince Dr. McGee to travel to another clinical
site. The site was an Oncologist office in Springfield, Missouri. We
discovered that the drug was being kept in the refrigerator freezer, which
was located in the staff lounge. Once again the drug was not being stored
at the proper temperatures and the drug was being subjected to a freeze
thaw cycle. Nor was the drug in a secure location. In fact there was not
any temperature monitoring occurring at all. Institutional Review Boards,
IRB's, are the gatekeepers for the safety and well fare of the human
subject, as mandated by the federal regulations. However we found out
that the Oncologist had never sought local IRB approval, although he
himself was an IRB member.
In October I discovered that the current version of the protocol had
never been submitted to the IRB, although it had been in use for seven
months. However, the OU IRB had approved a change in the inform
consent, which new title and contact information included St. John's
Medical Center. This is significant because the study was never submitted
to the St. John's IRB, even though St. John's IRB chair was also a member
of the OU IRB and he was present when the change was voted on.
I informed McGee that we were using an unapproved version of
the protocol and inform consent. He was surprised and disbelieved the
information. After a discussion he agreed that I should contact the OU
IRB administrator.
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The administrator met with Dr. McGee and I in late October. He
gave us some bad advice. He said that the IRB was not concerned about
monitoring, or study design issues. He also said that the problems
concerning the other sites and their approval was none of the IRB's
business, but rather a FDA matter. He instructed us to write protocol
amendments that he would get approved to cover us retrospectively.
In November protocol amendments were submitted to the IRB.
They included a change to allow patients to self-inject, increase the size of
the trial, change the statistical power, addition of a second drug GM-CSF,
and other modifications to the protocol that were already ongoing. These
are but a few examples that patient's safety and welfare were compromised
as mandated by the federal regulations.
I continued to be concerned about the trial. I had already started
staying late and reading everything I could find on the FDA website
concerning Good Clinical Practices, Good Manufacturing Practices, and
Good Laboratory Practices. The more I read the more alarmed I became.
I started asking questions about the manufacturing process and became
convinced that the lab was out of compliance as well. Many of the
required safety testing for new lots of vaccine had never been completed.
Plus the vaccine was not being manufactured in a sterile environment. Dr.
McGee continued to increase enrollment.
Soon thereafter I started following the chain of command within
the medical college and sounding the alarm for what I saw as serious non-
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compliance with the federal regulations that were put in place to protect
human subjects. Eventually this led me all the way to the top of the
medical college. By the time I blew the whistle in June of 2000 the
University had formed a committee that included the Dean of the Medical
College; the Director of the Office of Research; the IRB Chair; the Lab
Director; Dr. McGee; Our Department Chair and myself. The committee
was engaged in acts of cover-up instead of promptly reporting as required
by the federal regulations.
What led me to contact the Office of Human Research Protections?
It was the pledge that I took when I became a registered nurse, that I
would be a patient advocate. I was haunted by many images, but
particularly one image continued to eat at me. It was the inform consent
process. By now I knew that it had been coercive to promise subjects that
the melanoma vaccine offered hope of a cure.
Adverse events reporting were practically non-existent.
Unfortunelty, this sad situation of not reporting adverse events is the same
across the nation as was found by a study conducted by the University of
Maryland School of Medicine, Dr. Adil Shamoo.
Today the University had adopted many positive changes in the
way research is conducted. The President of OU is David Boren. I believe
in David Boren. In my opinion he is one of Oklahoma's greatest assets.
The University is in the process of implementing a model compliance
program and David Boren; the president of OU is committed to doing so.
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One of the changes is he has put in place is greater protections for whistle
blowers. I am a graduate of OU and actually in my own way I love the
University.
Now that I have moved from an academic medical center to a
community setting, I have recognized a new set of inadequacies in the
system. It is common practice for physicians in private practice to select
potential participants from their own patient databases. The inform
consent process in such instances needs to be more carefully monitored.
In such circumstances the relationship and role between patient and
doctor; researcher and participant becomes convoluted. Participants too
often are mislead concerning possible benefits and risks. Many physicians
who have experienced a loss of revenue due to the restructuring of health
care are using the monies paid for research as a way to supplement
income.
Conflicts of interest do not escape even those at the lowest level in
research operations, the research staff. I like many of my peers, job
performance is predominately gauged on the number of participants
enrolled and not necessarily on the quality of these data. I believe the
pressure on the research staff to meet enrollment quotas puts the inform
consent process at jeopardy.
Another threat to the research process and human subject
protections is the lack of adequately trained research personnel.
Individuals are frequently given the tasks of study coordination without
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proper training. Investigators often know even less than the research staff
about the expectations involved in research implementation. Certification
by all those involved in research would certainly be of benefit. I strongly
urge you to pass such legislation and I believe the concern for the
American Public's safety should mandate it.
I also urge you to pass legislation that allows the regulators to fine
individual investigators and to increase the budget that would allow for
more oversight. The regulators are hamstrung when it comes to
enforcement. We must give them the tools to hold individuals accountable
for their actions.
Lastly, an organization which I recently joined, CIRCARE,
Citizens for the Responsible Conduct In Research, is predominately
troubled by the fact that federal guidelines do not apply to privately
funded research (except for drug applications to the Food and Drug
Administration (FDA)), thus creating a two-tiered system of human
subject research standards and safeguards. I urge you to pass legislation
that would require all research to be subject to the jurisdiction of FDA and
OHRP; therefore, I appeal to you for the passage of the National Human
Research Protection Act.
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