15 Jul 2015

Paul Aisen’s departure from the University of California San Diego on June 21, to head up a new Alzheimer's institute affiliated with the University of Southern California, has precipitated an acrimonious, public feud that is being widely followed in the Alzheimer’s research community. On July 2, UCSD filed suit in California Superior Court against USC, Aisen, and eight other researchers. Almost daily since then, both sides have issued claims and counterclaims. Yesterday, USC sought a restraining order against UCSD to prevent it from accessing administrative areas of the ADCS servers, which could potentially unblind clinical trial data, and requesting continuance of a hearing scheduled for July 24. UCSD promptly filed a document in opposition. According to the San Diego Union Tribune, California Superior Court Judge Judith Hayes has ordered Aisen to reappear in court today, while she tries to sort out the legalities over ownership and administration of sensitive clinical trial data.

The initial complaint filed by UCSD claims, among other things, breach of fiduciary duty, breach of duty or loyalty by employees, interference with contract, and commission of computer crimes. Most of the charges stem from Aisen's attempt to transfer the grant for the Alzheimer's Disease Cooperative Study (ADCS) from UCSD to the new venture, called the Alzheimer's Therapeutic Research Institute (ATRI). Speaking to Alzforum, researchers in the field were concerned that the fracas might threaten the integrity of this $100 million-plus project for cutting-edge clinical studies.

Contractually, some ADCS studies allow for termination of the study if Aisen is not in charge, though Aisen told Alzforum he doubts that will happen.

"The situation is unprecedented," said Steven DeKosky, former vice president/dean at the University of Virginia, now deputy director of the McKnight Brain Institute at the University of Florida, Gainesville. "There have been disagreements over faculty transfers before, but none has ever reached this level of publicity." The debacle has spilled onto the pages of the San Diego Union Tribune, the Los Angeles Times, and Science.

Suit and Counter
Academic scientists tend to move several times during their career, and they often take their grant awards with them; however, since grants are usually contracted to universities and institutes, not to individual researchers, host institutes must agree to relinquish the funds. This is often done in a "gentlemanly" way, as some researchers put it, but the larger and more lucrative a grant becomes, the more reluctant a university can be to let it go, as seems to be the case here.

Aisen was appointed associate director of ADCS in 2003 while at Georgetown University in Washington, D.C. After ADCS founder Leon Thal died in 2007, Aisen became director, moved to San Diego, and grew the project’s size and national prominence. Aisen told Alzforum that he faced substantial administrative, financial, and infrastructural challenges at UCSD during the last eight years, despite repeated requests for improvement. Rachelle Doody, Baylor College of Medicine, Houston, and a member of the ADCS Steering Committee, told Alzforum that the National Institutes of Health supported the committee’s concerns about contracting and payment operations at ADCS, and that the NIH had expressed this to UCSD, as well. Alzforum’s request for related documents on the matter is pending at the NIH, and NIH officers declined to comment in the interim.

Other scientists who insisted their names not be used noted that contractual operations at ADCS seemed to be a major bone of contention. Aisen explained that the ADCS needs extensive legal support to manage hundreds if not thousands of contracts among study sponsors, clinical research sites, the NIH, and other trial partners, and that this had become a bottleneck in moving studies forward. Aisen's resignation from UCSD, along with those of several dozen members of the ADCS team he managed there, prompted the lawsuit. "Being sued for disloyal behavior is emblematic of the problem," Aisen told Alzforum.

The UCSD complaint reads more like a John le Carré novel than legalese. It charges Aisen and USC with conspiracy to misappropriate UCSD’s role in the ADCS, and it claims the eight named co-defendants who joined Aisen at ATRI acted as "double agents," conspiring to advance their personal interests and those of USC while working at UCSD. Sources told Alzforum that faculty and officers at UCSD were particularly irked after Aisen called a meeting of ADCS staff last May to tell them of his plans for moving to USC. According to the complaint, and UCSD employees, Aisen erroneously told ADSC staff that they would lose their jobs at UCSD after his departure.

UCSD also charges Aisen and his co-defendants with computer crimes and "conversion," a legal term for depriving an owner of his/her personal property without consent. This is because Aisen gave UCSD access to but not administrative control over ADCS data stored on an Amazon server after he left. The complaint claims that only UCSD is contracted to maintain and control ADCS data.

In a counter declaration filed July 7, Aisen claims that UCSD no longer has personnel qualified to maintain the electronic data capture (EDC) system he developed for the ADCS. He told Alzforum that upon leaving UCSD he tried to do what was right for the ongoing trials and their data. "That decision was the only way to protect the safety of [trial] participants and integrity of the data set, which must be in a form that satisfies the regulatory compliance system, with a chain of custody and tight audit trail," he told Alzforum. He said that he left all data on campus and that the current directors have the software, the code, and access to all the data. He insisted that contrary to some media reports, he never stole or erased data. The only thing UCSD lacks is administrative control, he said. Aisen said that even he does not even have passwords to fully access the system. This ensures that trial results are blinded to investigators.

USC has requested a temporary restraining order to block UCSD from trying to gain "root control" over the data. Declarations filed in support of this request note that only two people have such access to the EDC: Gustavo Jimenez-Maggiora, formerly director of informatics at the ADCS at UCSD, and Phuoc Hong, a programmer/analyst there. Root control allows the user to see all aspects of the data, including study participants’ personal information and clinical test data. Jimenez-Maggiora and Hong, now both at USC, were therefore the only people unblinded to study data handled by the ADCS. The declarations also warn that users who are unfamiliar with the proprietary EDC software could inadvertently delete or destroy the system if they had root control. UCSD demanded that the court deny USC's request for a restraining order, saying that UCSD owns the data and the defendants are simply trying to delay court proceedings.

Caught in the Middle
The quarrel has embroiled third parties. The ADCS coordinates several large clinical trials sponsored by public/private collaborations and runs at nearly 60 clinical centers in the United States, Canada, and Australia. Both sponsors and investigators have expressed concern that these trials continue to operate smoothly.

In its suit, UCSD claims that Aisen and colleagues tried to coerce Toyama Chemical Company to cancel contracts with UCSD and sign identical agreements with USC instead. Toyama sponsors the NOBLE study, which is run by the ADCS to test a neurotrophin called T-817MA in people with mild to moderate AD. Toyama was concerned with the overtures. "The complexity of these requested actions raises a series of significant logistical, contractual, and regulatory compliance issues," the company wrote to Aisen, according to the UCSD suit.

On the other hand, letters filed with Aisen's July 7 declaration indicate that sponsors and principal investigators of three other ADCS trials want Aisen to continue overseeing these studies. Eli Lilly & Company, which sponsors the A4 trial of solanezumab, wrote to UCSD to request that Aisen stay on, at least for the time being. "The current individuals running the study have the knowledge and experience of the trial and have been trained on Lilly Quality standards and completed a successful audit by Lilly and an external auditor. Until the time that a new staff has been named, trained and certified in a similar fashion, we ask that the A4 study remain with the current team in order to avoid unnecessary risk, inconveniences or disruptions," they wrote.

Likewise, A4 project director Reisa Sperling of Brigham and Women's Hospital, Boston, suggests that Aisen and his team run the trial at USC. "As Project Director of the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) Study, I am writing to express my strong support for Dr. Paul Aisen and the Alzheimer's Therapeutic Research Institute (ATRI) at University of Southern California (USC) to retain the oversight of the A4 Study data and day-to-day Alzheimer’s Disease Cooperative Study (ADCS) operations supporting the A4 Study. In particular, I strongly believe that USC ATRI personnel should continue to maintain the A4 Study data system during this transitional period, as this is clearly in the best interest of the ongoing A4 clinical trial," she wrote in an open letter.

Suzanne Craft, Wake Forest School of Medicine, Winston-Salem, North Carolina, requested that Aisen continue to oversee the ADCS Intranasal Insulin (INI) trial while the disputes are being resolved. (This trial is on enrollment hold because of a problem with the delivery device, not because of the dispute.) "It is the express wish of myself, as Principal Investigator, and the contracting office of Wake Forest as the award institution, that Dr. Aisen and his team retain operational oversight of the INI trial during resolution of any disputes with UCSD, including maintenance of and full access to the INI database and supervision of trial site operations," she wrote to William Mobley, who chairs UCSD’s department of neurosciences and was named interim co-director of the ADCS at UCSD along with ADCS medical director Michael Rafii. Mobley declined to speak with Alzforum.

And in an open letter, Christopher van Dyck, Yale University, New Haven, Connecticut, wrote that the university would transfer the Yale-UCSD subcontract for the FYN study to USC, and that during this transitional period ATRI personnel should maintain the FYN data system. "This is clearly in the best interest of the ongoing FYN clinical trial and the safety of its participants," he wrote. The FYN trial will test the fyn kinase inhibitor AZD0530 in mild AD.

What Happens Next?
Few researchers in the field would speak about this dispute on the record. Many were hoping for the best but preparing for the worst. Some felt the chance to arbitrate had slipped by; others feared that far beyond a tiff over an academic move, a criminal investigation might ensue if laws have indeed been broken. Some expressed concern for the co-defendants in the lawsuit who are now finding themselves in hot water over what was intended as a routine career move.

How this will affect the ADCS remains to be seen. Nina Silverberg, National Institute on Aging Program Officer for the ADCS, declined to speak with Alzforum, but she outlined the NIA’s position in an email to the ADCS steering committee that Alzforum obtained through a Freedom of Information Act request. "To clarify NIH policy regarding this situation, grants, including cooperative agreements (which the ADCS is) are awarded to institutions rather than to principal investigators. Therefore, currently, the ADCS cooperative agreement remains at UCSD," Silverberg wrote. In a follow-up email, Laurie Ryan, NIA Project Scientist for the ADCS, addressed concerns about continuity. "Our goal of course is to assure that operations of the ADCS network continue as seamlessly as possible, with a focus on the safety of study participants and the integrity and utility of data from ongoing ADCS studies," she wrote to the steering committee.

The legalities continue to play out in court. Today's hearing may determine who will maintain administrative control over the ADCS data, at least until another hearing scheduled for July 24. Meanwhile, an ADCS staffer at UCSD told Alzforum, “This is hard because we all like each other but now have to work across this chasm. I hope cooler heads will prevail.”—Tom Fagan

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References

Therapeutics Citations

1. Edonerpic
2. Saracatinib

Other Citations

1. UCSD complaint

Further Reading

No Available Further Reading