UCI Conceded ‘Unacceptable’ Monitoring

Faced with a fast-developing crisis at its fertility clinic, UC Irvine conceded earlier this year to federal investigators that its system for overseeing research on humans had suffered a severe and “unacceptable” breakdown.

The stunning admission came in a Feb. 4 letter to National Institutes of Health investigators who had dressed down UCI for failing to adequately monitor human research at its Center for Reproductive Health.

Federal investigators visited the university in January to probe allegations that its prized fertility experts might have blurred the lines between research and clinical practice.

The doctors--Ricardo H. Asch, Jose P. Balmaceda and Sergio Stone--have repeatedly denied any intentional wrongdoing.

Asch’s attorney, Ronald G. Brower, said that Asch “never did any research without prior approval. . . . You get to that point--his level--you don’t have to do unapproved research.”

The university alleged last week in court that the three clinic doctors transplanted patients’ eggs without their consent and used patients and their eggs for research without approval.

“This particular matter escaped detection as a research issue because the two usual checkpoints were either not involved or avoided altogether,” Executive Vice Chancellor Sidney Golub wrote to the NIH’s Office for Protection From Research Risks in a 14-page letter, one of a set of documents released Thursday.

Golub said the NIH investigators had “alerted the campus to a completely unacceptable situation in which human-subjects research may have been conducted without institutional review.”

The documents reveal for the first time the mad scramble by UCI officials to address the allegations after a warning that the NIH might pull the university’s authorization to conduct research on humans.

Dr. Michael Brodsky, who chairs the university’s Human Subjects Review Committee, said Thursday that his committee will meet with federal investigators next week to discuss plans to enlarge the research budget to create “basically a new police organization” to monitor research more closely.

“The university hasn’t particularly had a police type of mentality with regards to research,” Brodsky said. “We trust researchers to explain to us what they’re doing and present us with copies of their research and consent forms. If they don’t do that, we don’t have people running around looking under desks to see who’s doing something that they aren’t telling us about.”

The current revelations, however, will change all that, he said.

“We’re now realizing that we have to police the faculty or anyone who is going to put UCI’s name on a research paper,” he said. “I think people will realize that they’ve got to play by the rules and we’re going to be watching. . . . I think that will make things better here. The reality is we’re doing everything we think is appropriate.”

The tense exchange of letters between UCI and National Institutes of Health investigators that began one week after the federal investigators’ visit also shows the escalating concern that Asch, Balmaceda and Stone were increasingly out of the university’s control.

In one letter, NIH officials said they found the doctors to be startlingly unaware of the severity of the allegations, as well as basic protocols for human research.

As the university moved to sever ties with the doctors in late April, federal investigators sent an urgent letter to Golub by fax and overnight mail warning that the agency held the university responsible for all patient records.

“Let there be no doubt that OPRR expects UCI to have at its disposal all records necessary” to the completion of the federal investigation into human-subject research, OPRR senior policy adviser F. William Dommel Jr. wrote.

But by May 4, the letters show, Golub informed Dommel that the doctors were not cooperating with the university’s inquiry into research misconduct and that documents crucial to the investigation had been removed from the UCI Center for Reproductive Health.

Most of the federal investigators’ concerns hinged on problems with research by the doctors separate from allegations that doctors might have transferred eggs or embryos to other women without the donors’ permission.

The university appointed a three-member clinical panel of doctors last fall to explore the alleged misappropriation of eggs and other allegations of misconduct. But research problems also came to the panel’s attention.

After the January visit by federal investigators, UCI appointed another committee to explore the alleged research misconduct.

“Prior to the Feds coming here, we had no reason to think there was anything wrong at all,” Brodsky said Thursday. “The research people [at the university] were totally unaware.”

Among the problems later flagged in a university inquiry: three fertility research publications that relied on data from patient charts without obtaining proper human-research authorizations.

More significantly, the inquiry found that the doctors had conducted fertility research on patients without notifying the university, an April 7 letter from Golub to Dommel shows.

Brodsky, who is also part of a university committee appointed to figure out what might have gone wrong and how to correct the system’s inadequacies, said these studies were clear research violations.

Patrick Moore, Balmaceda’s attorney, said the research misconduct allegations have not been proved.

“They’re being investigated in the university, in accordance with university policies and procedures, and we fully intend to cooperate with that investigation--as long as it’s limited to issues relevant to the investigation,” he said.

The letters obtained Thursday show that the university took the research allegations seriously.

In the Feb. 4 letter to federal overseers, the university outlined its plan of action to correct problems. The measures included seizing control of all research and patient records, freezing human-subject research and appointing proctors to monitor all clinical research.

In a Feb. 21 letter to Golub, the OPRR’s Dommel said the moves had, “for the moment, avoided the need to restrict” the NIH approval for university human-subject research.