A Strict Protocol

With a blue-chip pedigree, Dr. William Frederick McGuirt Jr. used to be a respected member of the faculty at the Wake Forest University School of Medicine.

Now, he is scheduled to go before the N.C. Medical Board on charges that he falsified research data for an industry-sponsored clinical trial – violating a fundamental tenet of research ethics. If he is found guilty at a hearing in December, he could lose his license for at least two years.

McGuirt resigned from his job as an associate professor of surgical sciences in otolaryngology at Wake Forest in April, and began seeing patients at Piedmont Ear Nose and Throat Associates, a private clinical practice. He declined to comment on his case.

The incident provides a window into the world of industry-sponsored research, where pharmaceutical companies depend on the work of impartial academics, and universities compete to attract billions of dollars of research contracts each year.

Professors of medicine are often expected to earn a part of their salary from research grants. The need to conduct research, in addition to teaching and seeing patients, can amount to a high-pressure honor system.

“We’re creating an environment where it’s very hard,” said Bette-Jane Crigger, an expert on human-subjects research at the Hastings Center, a bioethics study group.
“There are so many pressures to do as much as you can that it can lead to error, or outright fraud.”

For Wake Forest, which through hustle and skill has become a major winner of public and private grants for research, the incident was the spark for re-examining the way that researchers are monitored. It also came at a time when the medical school was reorganizing the administration of clinical trials.

Pharmaceutical grants
McGuirt, 39, graduated from the University of North Carolina School of Medicine in 1989. He completed his residency at Presbyterian University Hospital in 1990 and a fellowship at Montefiore University Hospital, both in Pittsburgh, in 1994.

McGuirt also has family ties to the medical school. His father, Dr. William Frederick McGuirt, is the chairman of the otolaryngology department, where the younger McGuirt served on the faculty.

In 2001, he began working on two grants from Alcon Laboratories, a major pharmaceutical company with U.S. headquarters in Fort Worth, Texas, to study whether putting antibiotics drops into children’s ears after surgery helps prevent infections in the months after surgery. The research protocols specified that McGuirt was to follow up with patients within two to five days after surgery.

But he didn’t do that, according to officials at the medical school.

In February, the school began an internal investigation of McGuirt’s research after two nurse clinicians in the Office of Clinical Trials Research reported evidence of protocol violations to Dr. Sheila Vrana, an assistant dean for research and the research-integrity officer. According to the investigators, McGuirt tried to hide the violations by entering false data in the patients’ charts and signing off on them.

Based on the investigation, the school decided that the second clinical trial should be suspended. It also found problems with McGuirt’s data in the first study, said Mark Wright, a medical-school spokesman.

“We found that the protocol was not followed, but the documents indicated that it had been. In the medical school’s view, this is not the way the medical school conducts clinical trials,” he said.

McGuirt is widely regarded as a good doctor, Wright said, and no patients were hurt by his actions.

Dr. John Butterworth is the director of the Office of Clinical Trials Research. He wrote a long memo to Dr. William Applegate, the medical school dean, and Dr. James Smith, the associate dean, about the McGuirt incident and the medical school’s response.

“We were generally in the position of scrambling to gather our data-collection forms, drugs, etc., after Dr. McGuirt informed us that he had enrolled a patient and that he would need the drug in 30-60 minutes,” Butterworth wrote. “My colleagues in the OCTR (Office of Clinical Trials Research) and I saw much evidence of Dr. WF McGuirt’s disorganization and the frenetic pace of his clinical activity … I encouraged my staff to tolerate Dr. McGuirt’s disorganization (but to work to eliminate protocol violations) because there was no evidence for knowing and willful misconduct.”

In the June 6, 2002, memo, Butterworth wrote that he believed that McGuirt wanted to do industry-sponsored research to better his chances for promotion and attract more money for his own research.

Undermine validity of trial
Even if no one gets hurt, making up research data is ethically wrong, Crigger said.
“I would say that there is a dignitary wrong done to them,” Crigger said. “They (patients) weren’t partners in research – they’ve just been used.”

Clinical trials are carefully designed to test specific outcomes, she said. Faking data can undermine the validity of a trial, or stop it entirely.

“No sponsor is going to sit for that,” Crigger said. “They’re going to have to go before the FDA and show why the list of applications (for the product) can be extended. They need to be sure that the data is accurate. If the data is faked, potentially the integrity of the whole trial collapses.”

Wake Forest was one of several sites for the testing of a new application for Alcon antibiotics Ciprodex and Ciloxan, as well as a moxifloxacin solution in children and young adults who had had ear surgery, said Mary Dulle, an Alcon spokeswoman.

The clinical trial was suspended at Wake Forest, but not at the other sites, she said.
The legal, ethical and financial consequences of research fraud weigh heavily on officials at the medical school, Wright said. In this case, once the allegations of research violations were made in February, the school notified Alcon Labs, the Office of Human Subjects Research, the Food and Drug Administration and the N.C. Medical Board, Wright said.

No other industry-sponsored trials were stopped as the result of questions about McGuirt’s data, and no federal agency intervened, Wright said.

Large sums of money
A lot of money – as well as credibility – rides on a medical school’s ability to conduct clinical trials properly.

Researchers at Wake Forest bring in about 15,000 patients a year to take part in clinical research. Last year, the university won a record $146 million in research financing – less than 11 percent of it from industry-sponsored research projects such as the one in which McGuirt was participating.

Federal regulators rely on universities to oversee their own research programs, but do step in if discrepancies are found. For example, the federal Office for Protection from Research Risks shut down human-subjects studies at Duke University in 1999 after a random site visit in which investigators found inadequate oversight on the part of the school’s Institutional Review Board.

Last year, the government shut down Johns Hopkins University’s research program after the death of a healthy subject in an asthma-drug trial.

It’s impossible to know how often research fraud occurs, but there have been some recent high-profile cases, including the discovery that a physicist at Lawrence Berkeley National Laboratory used deliberately faked data in his quest to identify a new element.

“We’re hearing about more of it,” Crigger said. “Is it because it’s happening more often, or are we just hearing about it more? I don’t know.”

After the shutdown at Duke, Wake Forest instituted a mandatory ethics exam for faculty who are conducting research with human subjects.

Following the investigation into McGuirt’s data, medical-school administrators reviewed research policies and took steps to tighten research oversight further, Wright said.

A clinical-research investigator/coordinator certificate program began in February, and the school is developing a mentoring program for inexperienced researchers.

The school has also taken steps to hire a research-compliance officer whose only job will be to monitor clinical trials. It has also closed its Office of Clinical Trials Research – which mainly served to recruit industry sponsors – as part of an administrative reorganization that was already under way in February.

“No system will be foolproof,” Wright said. “But we want to make sure that we have learned the most from every situation.”

The N.C. Medical Board is expected to hear testimony in the matter Dec.19.
If McGuirt is found guilty of an ethical violation, the board could revoke, annul or suspend his license for a specified period of time. McGuirt could appeal the decision in Wake County Superior Court.

Published Oct. 20, 2002 in the Winston-Salem Journal