May 4, 2000
By PHILIP J. HILTS
BOSTON, May 3 -- Researchers at St. Elizabeth's Medical Center here failed to report the death of a patient in gene therapy experiments and might have contributed to the growth of cancer in another patient, whose condition was also reported improperly, investigators for the Food and Drug Administration have said.
Their accusation were made in April in a letter to the hospital and the chief researcher in the experiment, Dr. Jeffrey M. Isner, and was recently posted on the agency's Web site.
The experiment has been stopped.
The news comes as scientists, hospitals and companies sponsoring gene therapy experiments have been working to assure the public of the safety of the experiments after the death of a patient in a gene experiment at the University of Pennsylvania last year.
Jack Cumming, president of the Vascular Genetics Inc. of Durham, N.C., the company sponsoring the experiment at St. Elizabeth's, acknowledged today that there had been some "problems" in the gene therapy experiment. Mr. Cumming said the company would do everything it could to satisfy the F.D.A. in correcting the problems. He said he was "very optimistic" that positive results would be presented to the agency this summer.
Mr. Cumming said he would not dispute the agency's findings and said that his company had hired two outside groups to audit and monitor all the experiments it had begun around the country, including the one at St. Elizabeth's. The groups were hired after the company learned that the federal agency was writing a warning letter, he said.
Sonia Hagopian, a spokeswoman for the St. Elizabeth's, said the hospital took the warning letter very seriously, and added: "We are focusing all our resources on producing a thorough and thoughtful response to the F.D.A."
The hospital's public relations office said Dr. Isner would not be available for comment at this time.
The problems in the experiment were reported on Tuesday in The Washington Post and The Boston Herald.
In the experiment at St. Elizabeth's, which was jointly sponsored by Tufts University, a gene that makes a substance called V.E.G.F. (for vascular endothelial growth factor) was injected directly into the hearts of patients with blocked heart vessels. Researchers hoped the gene would start making the growth factor, which is the body's natural substance to make blood vessels grow.
Inspectors for the federal agency said they found several violations of the rules of the experiment in a routine check in March. One patient in the experiment died two months after receiving the experimental therapy, but the researchers failed to report the death to the agency. The agency is investigating to determine if the treatment was the cause of the death.
In another case, a patient was included in the study although he should have been kept out under the rules of the experiment. The patient was a heavy smoker and a small mass had appeared in one lung, the agency said. Because the experimental therapy used a chemical designed to increase the growth of blood vessels, the agency said, it was possible that it increased the supply of blood to the growing tumor.
The agency's warning letter noted that the St. Elizabeth's researchers saw the mass when it was less than a centimeter in July 1999, then again in August when it was two centimeters in diameter, but went ahead with the treatment on Sept. 21, 1999. Two months later, the agency said, the patient was hospitalized with chest pain, and the mass was found to have grown to five centimeters.
There was no evidence in the patient's records or the experiment records that either the patient or his doctor was notified of the growth of the mass, investigators said.
The hospital and the researchers have 15 days to tell the agency how they will correct the problems in the experiment. The F.D.A. has the authority to ban the researchers from future work using federal money.
This and three other experiments carried on by Dr. Isner were stopped when the agency first began its inspection in February and have not resumed.
Dr. Isner is a founder of the company leading the trials and is a major
stockholder in it.