VA Tells Doctor to Halt Studies

Months after a patient became dangerously ill from a medication overdose in a drug company-sponsored study, UC San Diego and Veterans Affairs officials have suspended research by a top liver specialist accused of violating regulations that protect volunteers.

Dr. Tarek Hassanein, a chief of clinical hepatology at the medical school who also has a limited practice at the affiliated veterans hospital, was ordered in April and May to stop enrolling patients in 15 clinical studies and account for “possible research misconduct,” according to documents from the two institutions.

The allegations suggest to some scholars that ethics problems persist within the VA system despite recent efforts to strengthen safeguards. Others say the institution’s firm response shows that heightened vigilance is working.

Officials acted after an internal VA probe allegedly found problems in three studies that Hassanein oversaw. In letters and memos obtained by The Times under the Freedom of Information Act, the officials cite preliminary findings and allege that Hassanein:

* Failed to obtain or properly document legally required informed consent from several research volunteers.

* Disregarded guidelines for recruiting patients to take part in studies, exposing them to “inappropriate” medications.

* Relied on an unlicensed employee to dispense study medications, in possible violation of California law.

* Did not notify officials when research volunteers had adverse reactions to study medications.

Hassanein denied the allegations, saying in an interview that they were based on misinformation or were paperwork glitches.

“None of the issues was really a major issue . . . other than making sure that every piece of paper was in the right place,” Hassanein, a hepatitis expert and transplant surgeon, said of the probe’s findings.

The documents tell a different story. Lucille Pearson, director of the UC San Diego office that monitors clinical research, wrote to Hassanein that the findings “raise questions about your standards as an investigator conducting research involving human subjects.”

The San Diego VA’s acting research chief, Dr. Robert Henry, wrote last month of Hassanein’s research subjects that the “the quality of care provided to these patients is questionable.”

According to the documents obtained by The Times, the VA opened its inquiry after a veteran with hepatitis developed serious anemia while taking a test medication. Over several months, half of the patient’s red blood cells disappeared, putting him at increased risk of a heart attack and other problems.

The patient, whose name was blotted out on the documents, was treated in the VA emergency room with a blood transfusion. Anemia is a known side effect of the antiviral drug product, a combination of interferon and ribavirin distributed by Schering-Plough. Hassanein said the patient is now off the study medication and doing fine.

At issue is whether the patient accidentally overdosed on the medication as a result of lax practices. Hospital authorities allege that the patient received the drugs in unlabeled containers in a brown paper bag from a research administrator not licensed by California to dispense controlled medication.

UC’s ethics committee “found this especially troubling since individuals enrolled in this research are very ill,” Pearson wrote.

Moreover, dispensing test medications haphazardly could invalidate study results because the dosages would be uncertain. “Handing people things in a brown paper bag isn’t science,” said George Annas, a law and medical ethics scholar at Boston University. A reporter described the findings to Annas, who was not involved in the inquiry.

Hospital officials also allege that Hassanein, contrary to regulations, failed to notify the ethics committee of such serious adverse reactions, the documents show.

Hassanein, who also practices at Riverside Community Hospital in Riverside, disputed that version of events. He said the administrator “did not give the patient medications because she had no access to the medication.” Instead, Hassanein said, the administrator only gave the patient a prescription. Hassanein said he thought it wasn’t necessary to report the case of anemia because it is a predicted side effect.

It is quite unusual for a medical center to suspend a researcher for alleged wrongdoing, medical experts say. Still, researchers run afoul of federal regulations and institutional policies fairly frequently.

Recent academic analyses have shown that about a third of clinical researchers surveyed failed to solicit proper informed consent from prospective volunteers. Some shortcomings were merely bureaucratic, such as misplacing consent records, but others posed a threat to subjects’ civil rights by minimizing a study’s risks, for instance.

Veterans Affairs research practices have lately been under a microscope. In 1999, U.S. officials temporarily suspended all studies at the VA medical center in West Los Angeles because of lax research oversight. Last year, a U.S. General Accounting Office audit of eight VA medical facilities found a “disturbing pattern” of failures to comply with human subject protections.

The VA system has created a new office to oversee research practices and commissioned an outside group to inspect clinical research facilities.

The UC San Diego School of Medicine also has had its ups and downs. In 1994, a Food and Drug Administration audit led federal authorities to briefly suspend all research using human subjects at the university. A 1995 survey commissioned by UC San Diego revealed “an inability to assure that all human subjects research was being reviewed” by the required ethics committee, according to a UC San Diego report.

The medical school and VA San Diego Healthcare System, both in La Jolla, share some teaching and research operations. Clinical studies at the VA facility are reviewed by a UC ethics committee.

The VA runs 172 medical centers nationwide, and the 355-bed San Diego facility has the most research funding of all: $42 million. UC San Diego’s medical school consistently ranks as one of the nation’s best.

Since suspension of Hassanein’s research, staffs at both institutions have been required to undergo ethics and regulatory training, a UC document says. Officials did not indicate how long they expect the suspension to last.

Henry of the VA said the inquiry into Hassanein’s research is nearly complete. “My job is to ensure that the health of veterans undergoing human research is absolutely protected to the top degree. I did not think it was in this case.”