Report Assails F.D.A. Oversight of Clinical
By GARDINER HARRIS
Published: September 28, 2007
WASHINGTON, Sept. 27 — The Food and Drug
Administration does very little to ensure the safety of the millions
of people who participate in clinical trials, a federal investigator
In a report due to be released Friday, the inspector general of the
Department of Health and Human Services, Daniel R. Levinson, said
federal health officials did not know how many clinical trials were
being conducted, audited fewer than 1 percent of the testing sites
and, on the rare occasions when inspectors did appear, generally
showed up long after the tests had been completed.
The F.D.A. has 200 inspectors, some of whom audit clinical trials
part time, to police an estimated 350,000 testing sites. Even when
those inspectors found serious problems in human trials, top drug
officials in Washington downgraded their findings 68 percent of the
time, the report found. Among the remaining cases, the agency almost
never followed up with inspections to determine whether the
corrective actions that the agency demanded had occurred, the report
“In many ways, rats and mice get greater protection as research
subjects in the United States than do humans,” said Arthur L.
Caplan, chairman of the department of medical ethics at the
University of Pennsylvania.
Animal research centers have to register with the federal
government, keep track of subject numbers, have unannounced spot
inspections and address problems speedily or risk closing, none of
which is true in human research, Mr. Caplan said.
Because no one collects the data systematically, there is no way to
tell how safe the nation’s clinical research is or ever has been.
The drug agency oversees just the safety of trials by companies
seeking approval to sell drugs or devices. Using an entirely
different set of rules, the Office for Human Research Protections
oversees trials financed by the federal government.
Privately financed noncommercial trials have no federal oversight.
“It’s crazy that we have all these different sets of rules,”
said Dr. Ezekiel J. Emanuel, chairman of the bioethics department at
the National Institutes of Health. “It would facilitate things a
lot if we had one agency overseeing things.”
Dr. Janet Woodthingy, chief medical officer at the drug agency,
acknowledged that it needs to put more “teeth” in its
enforcement. “We are working to address these problems very
aggressively,” Dr. Woodthingy said.
The case of Audine Graybill demonstrates the flaws in the system.
According to the F.D.A., in the spring of 2005, she decided to try
an experimental drug to treat mania associated with bipolar
disorder. The consent form that she signed on May 29 stated that she
could change her mind at any point in the study.
She checked into High Pointe Healthcare in Oklahoma City, a
psychiatric center owned by a psychiatrist, Dr. David Linden. On
June 3, Ms. Graybill changed her mind and asked to leave.
Dr. Linden refused to let her go.
On June 6, she was given the experimental medicine. Ms. Graybill’s
lawyer, Anthony Sykes, obtained a writ of habeas corpus for her to
appear in court and took the writ to the hospital, where the staff
refused to honor it and said it would not give it to Dr. Linden, Mr.
Mr. Sykes tracked Dr. Linden to another office and had him served
with the writ, Mr. Sykes said. Within hours, Dr. Linden’s lawyer
called Mr. Sykes and said Ms. Graybill was free to go. Mr. Sykes
took her home on June 7.
Ms. Graybill could not be reached.
More than nine months later, an F.D.A. inspector appeared at Dr.
Linden’s research center and uncovered myriad other problems.
The agency sent its warning letter more than two years after Ms.
Last November, the Oklahoma Board of Medical Licensure and
Supervision suspended Dr. Linden’s license for three months
because he had sex with two patients and gave them genital herpes
infections, according to board records. Dr. Linden, who also owns a
psychiatric center in Las Vegas, did not return repeated telephone
Dr. Linden has conducted clinical trials for most major
pharmaceutical companies and continues to do research, according to
his Web site.
The F.D.A. disqualified investigators from conducting further
clinical trials 26 times from 2000 to 2005 and disqualified their
data just twice even though the agency found serious problems at
trial sites 348 times in that period, the inspector general found.
While some of the report’s findings surprised ethicists, its
conclusion that the agency’s oversight of clinical trials is
disorganized and underfinanced has long been known and is, in many
ways, identical to criticisms leveled at other agency functions,
including its oversight of imported food, foreign drug
manufacturers, animal food and the safety of older medicines.
In each case, the size and complexity of the tasks facing the agency
have grown enormously as the number of inspectors for those tasks
has generally declined.
An inspector general’s report in 2000 criticized the oversight of
clinical trials and noted that the inspections mostly focused on
whether study information was accurate and not on whether human
subjects were protected. That is still true.
In the present report, the inspector general recommended that the
agency create a registry of all continuing clinical trials, an idea
signed into law by President Bush on Thursday.
The report also recommended that the agency create a complete
registry of research ethics boards, create a single comprehensive
database to track its research inspections and obtain greater
authority to regulate research assistants.
Senator Charles E. Grassley, Republican of Iowa, said the agency
“needs to implement these recommendations to meet its duty.”
Representative Rosa DeLauro, Democrat of Connecticut, said it needed
more money and guts.
“They’re passive, they’re reactive, and they often side with
industry over public health,” Ms. DeLauro said.
The agency’s reserve is apparent in some of its warning letters.
On May 24, 2005, an inspector, Barbara Breithaupt, went to the
office of Dr. Frank A. Wingrove of Ames, Iowa, and for weeks asked
to see records of his study of an experimental topical treatment for
periodontal disease. Dr. Wingrove refused. Dr. Wingrove did not
return telephone messages seeking comment.
More than two years later, the agency sent Dr. Wingrove a warning
letter. The inspector general’s report suggests that if Dr.
Wingrove promised to reform, the agency was unlikely to show up
again to see whether he had followed through.