HJLR Mar/Apr 2019

Healthcare Journal of Little Rock I  MAR / APR 2019 33 NIMH said it was never informed of these IRB-approved changes. “The changes were significant, because they increased risk to study subjects,” according to the November letter in which NIMH demanded repayment from the university. Five subjects younger than 10 enrolled in the study; Pavuluri said only a few that young were enrolled, and they got in “by mistake.” The IRB also failed to catch omissions in the consent forms, including informing sub- jects and their parents that lithium is not FDA-approved for children under 12 and there are alternative courses of treatment for bipolar disorder. Lithium is not FDA-approved for that age group because there have not been enough studies of its use. The drug continues to be tested in clinical trials; some psychiatrists say it is one of the best available treatments. As Pavuluri’s study progressed, there were other oversight failures. NIH policy recommends that individuals on a study’s data and safety monitoring board, which is tasked with observing a trial’s progress and the safety of its participants, “are in no way associated with the trial.” But the board for Pavuluri’s study included Pavuluri and a co- investigator, while a report by the monitor- ing board, submitted partway through the study, was prepared by a member of Pavu- luri’s research staff, records show. UIC officials said Pavuluri’s co-investiga- tor was originally an independent member before joining the research team and that there were other independent members on the panel. Nicholas Steneck, an emeritus profes- sor of history at the University of Michi- gan who was a consultant to the U.S. Office of Research Integrity, said it is difficult to understand how such a large research insti- tution could have such a “poorly function- ing IRB.” He called the UIC board’s failures “IRB 101 mistakes.” “In this case, it is the institution that failed,” he said after reviewing the case for ProPublica Illinois. “It could be a case of an overstressed system simply losing a sense of what they were responsible for and where they needed to draw lines.” In fact, UIC’s research oversight problems were not limited to Pavuluri’s studies. In 2014, prompted at least in part by the problems with Pavuluri’s research, the NIH and the OHRP conducted an on-site evalu- ation of UIC’s system for protecting human research subjects. Federal officials deter- mined that, in approving other research projects, university IRBs “sometimes lacked sufficient information tomake the determi- nations required for approval of research,” according to a December 2014 letter from OHRP to UIC. The letter cited a study — not a Pavuluri project — that the IRB approved before it had enough information and other studies for which research approval was expedited when it shouldn’t have been. UIC officials said in a statement that they have tightened oversight. IRBs, they said, now completemore detailed reviews of pro- tocols before approving changes, and they conduct more randomaudits of clinical tri- als to determine if researchers are follow- ing protocols. Still, in the case of Pavuluri’s studies, the officials put the blame on her. “The principal investigator is responsible for the ethical and professional conduct of sponsored research projects in compliance with applicable laws and regulations, includ- ing for timely and accurately informing the IRB of all changes in scope,” UIC officials said in their emailed responses to questions. But Amneh Kiswani, who served as an assistant director in the campus’ Office of Research Services, said the university bears at least some of the responsibility. When Pavuluri sought an amendment to expand the age of participants, for example, the IRB should have made sure that NIMH had already approved of that change, Kiswani said. “There are supposed to be controls and policies and procedures in place so these types of occurrences don’t happen,” said Kiswani, who left UIC in 2014. “In this par- ticular situation, both are responsible: the institution for failing to follow the rules for changes in scope and the investigator for not knowing her responsibility as a princi- pal investigator.” Carl Elliott, a professor of bioethics at the University of Minnesota, agreed that the NIMH’s determination of wrongdoing “sounds at least as critical of the IRB as it does” of Pavuluri. And he noted that the problems began even before her research got underway. “It baffles me how an IRB could give its ethics approval without reading the proto- col,”said Elliott, who also reviewed the case at ProPublica Illinois’ request. “If it doesn’t have the protocol, they can’t really know what it is they are approving. It doesn’t make any sense at all.” Pavuluri said she is shouldering more than her share of the blame when the uni- versity was also at fault. “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,” she said.