April 13, 2003
Nationwide Inquiry at Veterans' Hospitals
By ROBERT PEAR


WASHINGTON, April 12 - The Bush administration has ordered
a nationwide review of medical research at 115 veterans'
hospitals and has halted some studies after investigators found serious
violations of federal rules, including some that may have
contributed to the deaths of patients.

The Department of Veterans Affairs said it was
investigating the deaths of patients in research projects at hospitals in
Detroit, Albany and Fargo, N.D. The department also said it had
found "serious noncompliance" with federal rules at its hospitals in
Pittsburgh; Providence, R.I.; Martinez, Calif.; and Long Beach,
Calif, and detected problems at hospitals in Northampton, Mass.,
and Portland, Ore.

The new director of the veterans research program, Dr.
Nelda P. Wray, ordered the review last month after learning of cases
in which researchers falsified data and did not tell patients
about the risks of experimental treatments. "Those practices will
not be tolerated," Dr. Wray said.

Research is one of the principal missions of the Department
of Veterans Affairs, which spends nearly $1 billion a year on
about 15,000 studies involving 150,000 patients. Ethics committees
are supposed to monitor each study to protect patients.

An internal investigation by the department found that a
huge overdose of a prescription drug "led to the death of a
research participant in a clinical trial" at the veterans' hospital in
Detroit last year.

The department has joined federal prosecutors in a criminal
investigation of two researchers who worked at the veterans'
hospital in Albany. Fabrication of data in those studies may have
"contributed to the death of one or more patients," a memorandum
from the department says.

At the veterans' hospital in North Dakota, all clinical
research was halted on Feb. 28. Federal experts who inspected the
hospital said one patient had died and 22 had suffered adverse
reactions to drugs in research projects since September. The adverse
reactions were not promptly reviewed by the hospital, according
to the veterans agency's office of research compliance and
assurance, a watchdog body.

An official report on the Fargo hospital says that a doctor
there was listed, "without his knowledge or consent," as being
responsible for patients in a clinical trial comparing drugs for
high blood pressure. In a letter suspending research there, Dr.
Jonathan B. Perlin, deputy under secretary of veterans affairs, said
the study, involving 87 patients, was not properly supervised.

Some hospital administrators said they did not have enough
money or employees to comply with all the federal requirements.

Doctors at veterans' hospitals have done pioneering
research on spinal cord injuries and schizophrenia, helped develop the
implantable cardiac pacemaker and the nicotine patch, and
performed some of the first successful liver transplants. The agency has
also been a leader in analyzing medical errors.

But officials at those hospital now say they are reluctant
to discuss possible improprieties because they fear being sued.
Jayne M. Steubing, the widow of the Albany patient, Carl Steubing,
sued last month, asserting that researchers had falsified test
results and improperly enrolled him in the trial of a cancer drug,
hastening his death from stomach cancer.

"Our whole purpose is to ensure that this kind of thing
does not happen to other people," Mrs. Steubing said in an
interview.

Investigators said the Detroit patient, Cyril V. Krcmarik,
died after a series of medical errors.

The Department of Veterans Affairs and the Food and Drug
Administration faulted researchers who treated Mr. Krcmarik for
prostate cancer. He received a large overdose of dexamethasone, a
steroid to combat side effects of chemotherapy.

Mr. Krcmarik lived near Saginaw, Mich., so he was allowed
to fill his prescription at the veterans' hospital there. But,
investigators said in a recent report, the prescription was
"incorrectly rewritten" by a doctor at the Saginaw hospital and the
pharmacist further changed the instructions, and as a result the
patient used a nine-month supply of the drug in less than three weeks.
Moreover, the report said, the government twice refilled Mr.
Krcmarik's prescription and thus "missed opportunities" to correct
his dosing schedule before he died on April 2, 2002.

Mr. Krcmarik's daughter-in-law, Claudia S. Krcmarik, said
in an interview: "The veterans' hospital appeared to be a research
machine, using these elderly patients without enough oversight.
This is a vulnerable age group. You have people who are hard of
hearing, may have difficulty understanding instructions and tend to
trust their doctors."

Ann Talbot, a spokeswoman for the Detroit hospital, said:
"Somebody died. That was awful, and we are very seriously
concerned."

The researcher directing the study, Dr. Joseph A. Fontana,
said: "The patient was given more drug than he was supposed to
get. That was a pharmacy error. It will never happen again. I am
doing things differently now."

Federal officials told researchers at the V.A. Northern
California Health Care System, in Martinez, that they could not
recruit or enroll any new patients because they had not adequately
protected veterans in clinical research.

Inspectors from the Department of Veterans Affairs said the
California researchers did not properly assess the safety of
experimental treatments, overstated the benefits and did not
adequately explain the risks to patients, many with Alzheimer's disease
and other brain disorders.

Dr. Kenneth W. Kizer, who was under secretary of veterans
affairs from 1994 to 1999, said: "The problems at the V.A. are not
unique. Some prestigious universities have similar problems.
Clinicians view a lot of the federal requirements as administrative
hassles and do not take them seriously."

But the chief of the agency's research compliance office,
Dr. John H. Mather, said: "The rules are important. They reflect
the ethical underpinnings for the conduct of research, the need to
treat other human beings with dignity and respect."

The agency's Dr. Wray said all employees engaged in
clinical research would have to take courses in research ethics and
"good clinical practice." In addition, she said, all researchers must
have their credentials verified once a year.

Federal officials said such verification procedures might
have detected problems with one of the Albany researchers, whose
medical license was revoked by Iowa and Pennsylvania in the early
1990's.

Members of Congress recently introduced bipartisan
legislation to strengthen the research compliance office after learning
that the Bush administration was considering a proposal to reduce
its autonomy.



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