About 2,000 experiments at the Medical Center ground to a halt for four days last week when the federal government imposed a temporary ban on enrolling human subjects in research. The Office for Protection from Research Risks cited a host of organizational and administrative problems in Duke's procedures for approving human research projects, making the Medical Center the first major academic research institution to ever receive such a suspension.
Within four days, Medical Center officials created a corrective plan of action, met with OPRR representatives to improve administrative procedures and received the go-ahead to reinstate clinical research trials.
OPRR's action followed a five-month dialogue between federal officials and the Medical Center. In December 1998, representatives of OPRR, a tiny branch of the Department of Health and Human Services, observed the Medical Center's Institutional Review Board on a routine site visit and found many procedural deficiencies, including:
lack of quorum and consistent record-keeping at meetings of the IRB, which reviews and approves all human research;
an inconsistent number of members voting on specific protocols;
a failure to show how Duke followed the processes required by OPRR in reviewing research involving children;
the conflict of interest posed by having Duke's director and assistant director of grants and contracts serve on the IRB;
and a failure to conduct "substantive and meaningful continuing review" of ongoing projects.
In addition, Dr. Michael Carome of OPRR wrote in a December letter that "...such a large volume of human subjects research warrants more than one fully functional IRB."
Following the visit, OPRR asked Duke to submit a corrective action plan by Feb. 1. But this response and a second one submitted April 1 were deemed unsatisfactory.
In a May 10 letter to Chancellor for Health Affairs Dr. Ralph Snyderman, OPRR suspended the Medical Center's ability to enroll human research subjects. "In summary, OPRR finds the scope and pace of [the Medical Center's] implementation of corrective actions required... to be inadequate," according to the letter. "Indeed, the significant lack of progress demonstrated by [the Medical Center] over the more than three-month period since OPRR presented its findings to you... suggests a failure of leadership in [the Medical Center's] human subject protection system."
In an interview, Carome explained the decision. "It was certainly something that did not have to happen," said the chief of the Compliance Oversight Branch of OPRR, "[but] we felt that we had no choice."
Researchers suspended all studies that did not provide essential therapeutic benefits to patients while Duke officials scrambled to create an acceptable corrective plan. An ad hoc 12-member task force developed the plan and met last Thursday with OPRR officials in Maryland.
The next day, May 14, OPRR lifted the ban. "The plan they presented to us was very good and required minimal changes," Carome said. "We were satisfied with the scope and timing of their response."
Snyderman said the Medical Center should have acted sooner. "We did what we thought was appropriate under the conditions, but using the benefit of retrospective skills, we should have done it faster," he said. "It is fair to say it is a learning experience."
Under the corrective action plan, Duke will improve education for IRB members, increase the number of community and minority IRB members and re-review research projects approved at several IRB meetings earlier this year.
"It's going to be a lot of work, but it's doable," said task force member Dr. Richard Surwit, professor and vice chairman of the division of medical psychology.
Duke must also create a second IRB by June 1 and submit quarterly progress reports to OPRR.
Dr. Joseph Farmer, professor and acting chief of the division of otolaryngology, head and neck surgery, will head the second IRB. "With the assistance of the OPRR, our goal is to develop a model IRB program here at Duke," he said.
Dr. James Jollis, assistant professor in the division of cardiology, was one of several researchers directly affected by the suspension. "I had to have a patient sent home on the first day of therapy," he said. The patient, he explained, was complaining of chest pains and could have been treated using new therapy that may help severe coronary disease.
Researchers who had similar experiences with the temporary shutdown of research were cautious about pointing blame at either the Medical Center or OPRR.
"It was quite a shock when the initial ban came through," said Dr. Redford Williams, director of the Behavioral Medicine Research Center and professor of psychiatry and behavioral science.
Williams said he had to turn away a potential subject for a study on the effects of stress on biological and behavioral functions. "I think Duke should have responded more quickly. It would have been nice if OPRR had said, 'You have to do this now-or else'.... It's nobody's fault."
Snyderman said that last week's events point to a larger problem. "I believe there is a lot of confusion on the part of most clinical organizations as to the requirements for documentation in regards to IRBs," he said.
Although Duke is the first major academic health center to have its human research halted, OPRR has enacted similar but more serious punishments at three other institutions, most recently at the West Los Angeles Veterans Affairs Medical Center.
OPRR's actions against Duke last week have drawn national attention to the safety of human research subjects, but Carome said the action was not indicative of a new approach by the agency. "There are always investigations under our office," he said. "Our stance toward trying to ensure regulations are implemented has not changed."
Although Duke managed to have the ban lifted in just a matter of days, many said the shutdown could tarnish the Medical Center's reputation as a leading research institution. "The credibility that we have both to patient confidence and [to] those who might work with us-to have this type of situation occur might erode this confidence," Jollis said.
President Nan Keohane, however, said the University's prestige is undiminished. "Duke earned its reputation by the great many accomplishments by a great many people," she said. "We are convinced that the work that is done at the Medical Center is done to the highest standards. We do not feel it reflects on our stature as a premier research institution."
Katherine Stroup contributed to this story.
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