USC Neuroscientist’s Research and Stroke Drug Trial Under Scrutiny
Investigation Prompts NIH to Suspend Clinical Trials
Introduction
In a bombshell revelation, a group of whistle-blowers have raised concerns about the integrity of Dr. Berislav V. Zlokovic’s neuroscience research and the safety of an experimental stroke treatment developed by his company. This has prompted the National Institutes of Health (NIH) to pause clinical trials for the drug, 3K3A-APC.
Retractions, Corrections, and Expressions of Concern
Three of Zlokovic’s research papers have been retracted due to data and image manipulation. Seven additional papers have received corrections, with one receiving a second correction after the new data was also found to be problematic. A further paper has been flagged with an expression of concern.
Volume of Retractions Highlights Systemic Issues
“The high volume of retractions, corrections, and expressions of concern is highly unusual, especially in influential journals,” said Dr. Matthew Schrag, an assistant professor of neurology at Vanderbilt who co-authored the whistle-blower report independently of his university affiliation.
USC Initiates Internal Review
Both Zlokovic and USC have declined to comment, citing an ongoing review initiated in response to the allegations. The university emphasizes its commitment to research integrity but is bound by confidentiality regulations.
Attorney Defends Zlokovic, Cites Typical Scientific Process
Zlokovic’s attorney dismisses the concerns as based on incorrect information and faulty premises. He asserts that corrections and retractions are a normal part of the scientific process.
Authors Challenge Assertion of Typical Scientific Process
Critics dispute this assertion. “Authors should be able to provide original data if errors are genuine,” said Elisabeth Bik, a microbiologist and scientific integrity consultant who co-wrote the whistle-blower report. “The numerous errors and signs of image manipulation raise deeper concerns.”
Whistle-Blower Report Alleges Data Manipulation in 35 Papers
The whistle-blower report submitted to NIH identifies alleged doctored images and data in 35 research papers where Zlokovic is the sole common author.
Concerns about Blowback on Stroke Trial
Schrag emphasized the heightened stakes when unreliable data forms the basis of clinical trials. “Patients undergoing such trials are often at their most vulnerable medical moment,” he said.
ZZ Biotech’s Drug Faces Scrutiny
Zlokovic co-founded ZZ Biotech, which is developing 3K3A-APC. USC received an initial grant of $4 million from NIH for Phase III trials of the drug on 1,400 patients.
Phase II Trial Results Questioned
The Phase II trial, published in 2018, reported higher mortality and disability rates among patients receiving 3K3A-APC compared to placebo. However, these differences were not statistically significant.
USC Neurologist Defends Trial Safety
Dr. Patrick Lyden, a USC neurologist who was involved in the Phase II trial, disputes claims of undue risk. He attributes the errors in the published data to an oversight and believes the trial demonstrated the drug’s safety.
Questions Linger over Trial Pause
Despite Lyden’s defense, Schrag highlights the red flags in the trial data, such as a trend towards higher early mortality and worse disability outcomes for patients receiving the drug. He argues that these concerns warrant scrutiny, especially in light of the ethical issues surrounding Zlokovic’s pre-clinical research.
NIH and ZZ Biotech Remain Silent
NIH declined to provide specific reasons for the clinical trial pause, citing confidentiality. ZZ Biotech’s CEO also declined to comment or provide information on the trial’s status.
Zlokovic’s Academic Career and Affiliations
Zlokovic is a renowned researcher in blood-brain barrier and its role in stroke and dementia. After a brief departure, he returned to USC in 2011 as department chair and director of the Zilkha Neurogenetic Institute. USC confirmed that he retains these positions despite the ongoing review.
Conclusion
USC’s internal review continues to investigate allegations of research integrity issues surrounding Dr. Zlokovic and his neuroscience research. The suspension of clinical trials for 3K3A-APC has raised questions about the drug’s safety and the reliability of the underlying data. The outcome of these investigations has implications for the affected patients, the reputation of USC, and the broader scientific community.