For a year, the University of Illinois at Chicago has downplayed problems in its oversight of the work of a prominent child psychiatrist who violated research protocols and put vulnerable children with bipolar disorder at risk.
But newly obtained documents show UIC acknowledged to federal officials that it had missed warning signs that Dr. Mani Pavuluri’s clinical trial on lithium had gone off track — problems that resulted in the university having to repay a $3.1 million federal grant.
The records show UIC’s Institutional Review Board, the university committee responsible for protecting research subjects at the school:
- Improperly fast-tracked approval of Pavuluri’s clinical trial.
- Didn’t catch serious omissions in the consent forms parents were required to sign.
- And allowed children to be enrolled in the study even though they weren’t eligible under the research guidelines.
The review panel’s shortcomings violated federal regulations meant to protect human subjects, putting it in “serious non-compliance,” according to one of five letters UIC officials sent federal officials.
The university released those letters only after a nearly yearlong appeal by ProPublica Illinois under public records laws.
Despite what the letters say, UIC continues to place blame for the problems solely on Pavuluri. As it did last year when ProPublica Illinois revealed Pavuluri’s research misconduct and the university’s failures of oversight, the university now says that “internal safeguards did not fail” and that its researchers are “responsible for the ethical and professional conduct” of their own projects.
The stories last year, co-published with the Chicago Sun-Times, revealed that, in a rare rebuke, the National Institute of Mental Health ordered UIC in November 2017 to repay millions in grant money it received for one of Pavuluri’s lithium studies.
But the University of Illinois system withheld or redacted some documents, citing federal and state privacy laws. After the university declined to turn them over, ProPublica Illinois appealed to the Illinois attorney general’s public access counselor. The agency decided last month that the school had improperly refused to release all or parts of five letters UIC sent the National Institute of Mental Health and the U.S. Department of Health and Human Services’ Office for Human Research Protections. Other requested records remain under review by the attorney general’s office.
In one of the newly released letters, dated March 22, 2013, James Fischer, then UIC’s director of the Office for the Protection of Research Subjects, told the Office for Human Research Protections an initial internal audit had determined that the university review panel’s shortcomings had “the potential to compromise the integrity of the human subjects protections program.”
Another letter from Fischer, sent in October 2015, explained why a university investigative panel concluded children probably were harmed by Pavuluri’s studies. The university has refused to release the panel’s report, but a summary — which the October 2015 letter refers to — says children were found to have been harmed based on reports from parents and “a preponderance of evidence.”
“It is clear that it is not because of [Pavuluri’s] actions that harms may have been avoided,” the panel concluded, according to part of the report Fischer included in his letter. “It is despite her actions that no subject came to worse harm.”
Pavuluri’s “Affective Neuroscience of Pediatric Bipolar Disorder” study began in 2009, aiming to use imaging to examine how the brains of adolescents with bipolar disorder functioned before and after taking lithium. The brain scans were compared with images from healthy, unmedicated children.
The study was almost complete, and the money spent, when it was shut down in 2013. That was after one of the young subjects became ill after withdrawing from other medication to begin receiving lithium for the study.
According to the study protocol the National Institute of Mental Health had approved, subjects should not have been able to participate if they previously had taken psychotropic medication. The university’s review board did not approve medication withdrawal, records show.
The child’s hospitalization was reported to the review board and to federal officials, who requested more information. UIC conducted the initial audit and then an investigation, keeping federal officials informed of its findings over the next two years.
The National Institute of Mental Health ultimately found that Pavuluri and the UIC review board failed in numerous ways and demanded the $3.1 million be refunded. They determined that the study had been compromised and that its results had no scientific merit.
The university previously had returned about $800,000 for two of Pavuluri’s other federally funded projects that also were shut down early when similar problems were uncovered.
The newly obtained documents regarding Pavuluri’s work describe poor record-keeping that included missing dates and identification numbers for the research subjects, among other problems, making it difficult for university officials who reviewed the research to tell who took part in the trial and the details of their participation.
The records also contain details that explain why 89 of the 103 children who participated should have been ineligible, for reasons including a history of substance abuse, seizures or suicidal tendencies.
Though the federal grant limited the study to teenagers between 13 and 17, the university review board approved Pavuluri’s request to also include 10- to 12-year-olds despite a prohibition by the National Institute of Mental Health against doing this and a lack of proper documentation by Pavuluri about the reasons for the expansion.
Pavuluri veered even further from the protocol, records show, enrolling 8- and 9-year-olds in the study.
In another significant violation, the university review board approved the inclusion of study subjects as long as they hadn’t taken lithium, though the federal grant barred participation of anyone who previously had taken any psychotropic medication. Nearly 25 percent of the children and teenagers in the study withdrew from or tapered off other medications before participating, including the girl whose illness ultimately led the study to be shut down.
The federal mental health agency has said it was not informed about the eligibility changes to allow younger participants and those who had been on other medications. It said “the changes were significant because they increased risk to the study subjects.”
In written responses to questions, a UIC spokeswoman said no university employees were disciplined for the noncompliance and that the university did not fail in its oversight.
UIC officials have said they took appropriate steps once they realized there were problems with Pavuluri’s research, including reporting the concerns to the federal agencies, suspending her research and ultimately ordering her to retract journal articles. They have said UIC “does not allow non-compliance” and that research on human subjects “was performed upholding the highest standards in ethical and responsible research conduct.”
In its only university-wide communication about Pavuluri’s research, sent last spring, days after the initial story about the problems, school officials discussed Pavuluri’s missteps but did not mention the review board’s failings, saying UIC “did not have any systemic issues of lax research oversight.”
But “corrective actions” were taken, including changes to the university’s review process, records show. Review board panels were instructed to focus on the research protocol when reviewing researchers’ requests to make changes to ensure compliance with the approved criteria.
UIC did an audit to determine whether consent documents research subjects in other studies were given followed the rules. The UIC spokeswoman wouldn’t discuss the results of that audit, but one of the documents indicates the audit found deficiencies in consent forms for 11 of the 28 protocols examined.
Pavuluri, who founded UIC’s Pediatric Mood Disorders Clinic when she joined the university in 2000, retired in June and has opened a private practice, the Brain and Wellness Institute, in Lincoln Park.
She didn’t respond to an interview request. But last year she said her mistakes were oversights and that she made decisions in the best interests of her patients. She said she received minimal research guidance and training from the university, though she received $7.5 million in National Institutes of Health grants while at UIC.
Pavuluri said then that she expanded the criteria for who could enroll in the study because it was difficult to find enough subjects within the narrow age range who were not taking other medication.
She said university officials placed too much blame on her, rather than recognizing those responsible for oversight also were responsible.
“It was in their interest to kind of maybe see this as one person’s mistake [rather] than the responsibility of the IRB as well,” Pavuluri said.
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UIC officials have said that although there were problems with Pavuluri’s research, a review of her medical practice found she provided “high-quality patient care.”
Still, after the reports last year, the Illinois Department of Financial and Professional Regulation opened an investigation into Pavuluri, issuing three subpoenas to UIC in August and September seeking records related to Pavuluri and her research.
Results of state investigations of doctors aren’t made public unless the department imposes discipline.
Pavuluri’s research also has been under investigation by two divisions of HHS, according to subpoenas, emails and other documents: the inspector general’s office, which examines waste, fraud and abuse in government programs, and the Office of Research Integrity, which reviews claims of scientific misconduct.
Redacted documents before and after
Jodi S. Cohen is a reporter for ProPublica Illinois.