The University of Louisville plans to resume a highly scrutinized research study that was previously halted amid data collection and oversight problems.
Earlier this year, a division of the U.S. Department of Health and Human Services made the rare decision to stop funding a U of L study that evaluated treatments for paralyzed patients.
Last month, a different federal agency -- the U.S. Office for Human Research Protections -- found several violations in researcher Susan Harkema’s trials but declined to levy any sanctions. The federal agency accepted U of L’s pledge that it had remedied the issues.
Harkema, a prominent spinal cord researcher and U of L fundraiser, previously vowed to restart her trial if the federal inquiry cleared her.
Gary Mans, spokesman for U of L Health Sciences Center, said researchers will resume enrolling new participants in all the challenged studies. That includes the discontinued study, which measured the effect of the muscle relaxer Baclofen on paralyzed patients using treadmills.
Mans said in an email that researchers have implemented improvements for trial participants.
“All allegations of increased patient risk and adverse event reporting were found to be unsubstantiated,” Mans said.
Several allegations were, in fact, substantiated, according to the letter issued last month to U of L by the federal agency.
The letter, authored by Kristina Borror of the Division of Compliance Oversight, noted several violations: unanticipated problems weren’t reported to institutional officials, research was changed without permission, and Harkema used an inadequate informed consent document.
Michael Carome, director of the health research group at the nonprofit watchdog group Public Citizen, said the university is trying to put a positive spin on the letter. The letter, Carome noted, included examples of researchers not monitoring potential problems that are meant to ensure the safety of patients.
“Those types of findings are serious,” said Carome, who was associate director for regulatory affairs at the U.S. Office for Human Research Protections for eight years. “That type of noncompliance can put subjects at risk. I think the university is downplaying the significance.”
Carome reviewed the documents at KyCIR’s request.
The U.S. Office for Human Research Protections investigation was spurred by complaints about Harkema-led trials from now-former colleagues, one of whom has since filed a whistleblower lawsuit against U of L.
In July, experts told WFPL’s Kentucky Center for Investigative Reporting that the study problems might have compromised the accuracy of its research for vulnerable patients who hope to walk again.
An internal U of L report found evidence of problems in the Baclofen study. (Read "Top U of L Researcher Loses Federal Funding For Paralysis Study")
The findings included:
- possible adverse events that weren’t reported
- “inconsistencies” that led some patients to pay for therapy when insurance stopped covering part of the treatment
- patients signing the wrong consent forms
- records that lacked follow-up data or information about patients’ medication compliance.
The internal report played a role when the division of the U.S. Department of Health and Human Services pulled its funding. The funding agencyquestioned the validity of the data collected in light of a lack of follow-up records or even medication checks.
The problems raised "critical questions about the investigators' ability to reliably measure" the very questions they sought to answer about the drug, the agency said.
Harkema said in a June interview that record-keeping problems were fixed, patients were not put at risk and concerns about her study were overblown by disgruntled ex-colleagues.
Harkema didn’t respond to a request for comment. Mans said Tuesday he didn’t know who will fund the re-started study.
TheU.S. Office for Human Research Protections found that research protocol was changed in the Baclofen study without institutional approval and researchers continued training sessions with a participant who had swelling and instability, but wasn’t given an X-ray.
The investigation also found that participants in the Baclofen study “may have been misinformed” on the costs to participate.
Experts told KyCIR that it’s unusual for a study participant to be responsible for any costs; the complaint against Harkema alleged that patients who weren’t expecting to pay anything were asked to pay up to $15,000 to stay in the study after their insurance benefits were exhausted.
U of L said it had educated Harkema on reporting guidelines, revised consent forms, and asked a physician to review all research medical reports, among other tweaks. The federal protection agency found that U of L’s own corrective actions were sufficient.
“At this time, there should be no need for further involvement by our office in this matter,” the letter said.
Although the feds could take action against the institution or the researcher, action stronger than a letter of findings like it issued to U of L is very uncommon, according to Carome.
Kate Howard can be reached at khoward@kycir.org and (502) 814.6546.
Disclosures: In 2015, the University of Louisville, which for years has donated to Louisville Public Media, earmarked $3,000 to KyCIR as part of a larger LPM donation. University board member Stephen Campbell and former member Sandra Frazier have donated.
