A longtime heart specialist at the University of Arizona has been banned from conducting research on humans due to violations he committed during a nationwide study of heart-failure patients.
The cardiologist, Dr. Paul Fenster, said his violations involved only "clerical mistakes."
However, UA officials said it remains unclear whether the violations caused patient harm.
"The heart-failure patients in the study were very ill, which makes it difficult to determine if there was actual patient harm," said George Humphrey, spokes-man for the Arizona Health Sciences Center, one of 130 U.S. research sites involved in the four-year study, with results published in the New England Journal of Medicine.
Fenster is the only UA researcher ever forbidden to conduct human-subject research, although the university did fire a prominent Alzheimer's disease researcher in 1998 for scientific misconduct.
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An investigation by the U.S. Food and Drug Administration cited Fenster for reporting the death of one patient six months after it happened, but it did not say any of Fenster's violations actually caused the death.
The FDA cited nine "failures" that it said Fenster committed during the study. They involved not following regulations for "protecting rights, safety and welfare of subjects"; not obtaining informed consent from patients; and not maintaining complete and accurate records.
Fenster led the UA arm of the study, which tested an experimental pacemaker on patients with moderate to severe heart failure. The effort enrolled a total of 1,500 patients, including 31 at the UA.
The study found that the device — a biventricular pacemaker — improved symptoms and prolonged the survival of certain patients, according to a 2004 report in the New England Journal.
Fenster's problems first were uncovered during a routine audit of research studies done by the university, Humphrey said.
After irregularities were found, the UA contacted the FDA, which then conducted a two-month, on-site investigation last fall. That resulted in an FDA warning letter to Fenster in March and the UA's permanent ban on further human research by him.
"The doctor and the university were at odds about the severity of these irregularities, so we bowed out and called the FDA," Humphrey said.
"What this means is that the University of Arizona has a very good program in place to protect human subjects," he said.
"That's how these problems came to light in the first place."
In his response to the FDA's findings, Fenster wrote: "A thorough review of the evidence clearly demonstrates that all of my errors were clerical mistakes, and that these errors had absolutely no impact on patient safety or well-being and did not compromise the scientific validity of the data."
Fenster's patient data were accepted and included in the final study results, despite the violations. The study was sponsored by Guidant Corp., the manufacturer of the device.
Fenster also wrote that the FDA did not recommend punitive action against him and that the UA's decision "that I be harshly judged and punished" was based on "several serious errors and incorrect conclusions."
Most families of patients enrolled in the study "expressed their gratitude for the excellent care we provided," he wrote. "The families of those who died thanked us for our efforts."
The FDA is now reviewing Fenster's responses to the warning letter and his "corrective-action plan" before deciding on any final action against him.
Among the "failures" cited by the FDA in its warning:
● A physician not approved for the study implanted devices in three patients and attempted to implant one in a fourth.
In his response, Fenster said the error was due to a "miscommunication" between him and Guidant, and he acknowledged that there should have been a written clarification of this physician's status in the study.
● A patient was enrolled in the study before his eligibility was determined.
Fenster said the patient had suffered heart failure for 5 1/2 months instead of the required six months, which he thought was allowed due to the severity of the patient's condition.
● Screening and enrollment records were not maintained for any of the patients.
Fenster said his nurses were told such records were necessary only for centers that were not enrolling enough patients.
● Fenster failed to report the death of a patient for six months and the kidney transplant of another patient for seven months, despite the requirement that all "adverse events" be reported within five days.
Calling these "simple clerical errors," Fenster said the study sponsor was notified of the death within days, and he did not realize he had failed to report the transplant.
● Two patients did not sign proper consent forms.
Fenster said one patient did initial and date the consent form, while the other mix-up was due to a printing mistake.
● Progress notes for three patients had unsigned and undated additions.
Fenster described these as "clerical errors" and noted that they were a small number "among thousands of notes" during the course of the study.
● An electrocardiogram for one patient was missing.
Fenster responded that it was only one of "hundreds obtained" during the study.
