Attorneys defending Duke University are preparing to argue that no patients were harmed in the institution’s phase II clinical trials of genomic predictors that were later shown fraudulent.
The technology in question came from the laboratories of Duke stars Joseph Nevins and Anil Potti, and was based on findings that, from the outset, seemed too good to be true—and were ultimately discredited and retracted.
The suit claims negligence, breach of fiduciary duty, unjust enrichment, infliction of emotional distress, loss of chance, battery, deceptive trade practices, civil conspiracy and obstruction of justice.
The trial is scheduled to begin Jan. 26 at Durham County Superior Court. Altogether, 117 patients enrolled in the three clinical studies at Duke.
The essence of Duke’s argument—which forms the basis of a flurry of motions for a partial summary judgment—is that patients who entered the clinical studies were, for the most part, in late stages of disease and that the predictor models were used to assign them to existing therapies.
The plaintiffs’ attorneys argue that Duke had ample opportunities to recognize that the technology tested in the three trials was fraudulent. Instead, in the spring of 2008, Duke officials silenced a whistleblower, frustrated an NCI inquiry, and, in the fall of 2009, set up a biased internal review of the three trials.
On top of that, the deans who were directly involved in silencing the whistleblower later told a committee of the Institute of Medicine that no whistleblower had come forward from Potti’s lab.
These signals—had they been taken seriously—could have led Duke to stop the three clinical experiments it was conducting.
The consent forms signed by the patients who enrolled in the studies extolled the potential of Duke’s technology.
This genomic predictor looks at hundreds of genes (pieces of DNA—a short form of deoxyribonucleic acid that contains information needed to construct and operate the human body) in your tumor. In initial studies, the genomic predictor seemed to determine which drug would be effective in a given patient with an accuracy of approximately 80%. The genomic predictor is still being tested in research studies and is therefore considered investigational.”
As the case moves to the courtroom, it will demonstrate how the fundamentals of medical ethics translate into the context of legal disputes.
“There is no question that serious ethical lapses occurred,” said Wylie Burke, professor in the Department of Bioethics and Humanities and adjunct professor in the Department of Medicine (Medical Genetics) at the University of Washington.
“The first set of lapses related to Potti’s research misconduct. He evidently either fabricated or manipulated data to support the validity of the genomic predictor test that was presented as a scientific breakthrough and then used in clinical trials.
“Were others implicated in this misconduct? It is hard to know, but certainly there was a failure of effective research participation on the part of his collaborators. At best, the sequence of events illustrates the willingness of others on the scientific team to accept Potti’s results without questioning or even fully understanding them; at worst, others may have been complicit in the misconduct.
“The second set of lapses was the failure on the part of several people at Duke to take concerns about Potti’s research seriously,” said Burke, who was asked by The Cancer Letter to review several court filings. “The unwillingness to respond effectively to Perez’s concerns might be a symptom of the hierarchical bias often seen in academic institutions: the word of a lowly medical student (even an obviously talented one, who has carefully substantiated his concerns) tends to carry much less weight than that of a professor (problem in itself).
“At the very minimum, however, Nevins should have followed up on Perez’s concerns with an independent look at the data, if only (in his own mind) to assure himself that all was well. The concerns expressed by [MD Anderson Cancer Center statistician Keith] Baggerly [who led an independent investigation of the Duke results] and colleagues should also have led to re-evaluation of the data. Much would have turned out differently if Nevins had done so, and his failure on this point remains incomprehensible.
“The third set of lapses was the cover-up,” Burke said. “It is difficult to escape the impression that at a certain point officials at Duke decided to circle the wagons and deny knowledge of events (such as Perez’s communication of concerns) in order to limit damage to the institution. That they did so through several stages of investigation, including in testimony to an IOM committee, is deeply troubling.
“I defer to legal experts on the implications from the perspective of the law. It is probably accurate to say that the patients enrolled in the trials were by and large not harmed by their participation, in the sense that their life expectancy was likely not changed. Yet the claim that patient’s quality of life was harmed by decisions she made based on Potti’s false assertions must be taken seriously.
“And there are harms that are not effectively addressed by the courts. It is a harm to be lied to; it is a harm to be given false hope. The harm is first and foremost to the research participants, but it is also a harm to the research enterprise itself.”
No Harm Done?
Duke’s motions for a summary judgment argue that the case should turn on North Carolina law, as opposed to established ethical constructs.
In an effort to determine the burden of proof that has to be met by the plaintiff to demonstrate negligence per se, Duke’s motion states that standards contained in the 1979 report by the National Commission for protection of human Services of Biomedical and Behavioral Research, known as the Belmont Report, don’t create obligations under North Carolina law. Similarly, they argue that the federal law, Title 45 part 46 of the Code of Federal Regulations, which sets out requirements for research institutions, is not a part of North Carolina law, either.
Duke basically states that it did nothing wrong.
“Plaintiffs cannot show that a different course of treatment would have made any difference in their care or chance of survival,” the Duke motion reads. “Expert testimony in this case has not established that any clinical trial available in the United States in 2010 would have prolonged plaintiffs’ life expectancy or treated them more effectively. Therefore, plaintiffs cannot meet causation of damage elements of their negligence per se claim.”
Another court filing deals specifically with the case of Juliet Jacobs, a patient with metastatic lung cancer who—with Potti’s knowledge—made a recording of the now disgraced doctor as he presented the trial to her. Juliet’s widower, Walter, is one of the plaintiffs.
Duke attorneys argue that in that specific instance, “these defendants did not abuse, breach, or take advantage of Mrs. Jacobs’s confidence or trust. Instead, they were open, fair, and honest with Mrs. Jacobs and her husband regarding her prognosis and treatment options. Mr. & Mrs. Jacobs were made aware that the clinical trial may increase, decrease or have no effect on Mrs. Jacobs’s likelihood of responding to chemotherapy. They were also encouraged to seek other treatment alternatives.”
Duke’s filings also hold that “the undisputed evidence in this case has established that there was no clinical trial or other treatment available in the United States in 2010 that would have cured Mrs. Jacobs’s cancer or prolonged her life expectancy. Plaintiff cannot show that a different course of treatment would have made any difference in Mrs. Jacobs’s chance of survival.”
Duke attorneys are not representing Potti, who was dismissed from the university. However, they are representing Nevins, the deans, the IRB chair and the spinoff company that was going to commercialize the Nevins-and-Potti inventions.
The defendants argue that the plaintiffs cannot prove “negligence per se” claims because they cannot show that there was “(1) a duty created by a statute or ordinance; (2) that the statute or ordinance was enacted to protect a class of persons which includes the plaintiff; (3) a breach of the statutory duty; (4) that the injury sustained was suffered by an interest which the statute protected; (5) that the injury was of the nature contemplated in the statute; and (6) that the violation of the statute proximally caused the injury.”
Plaintiffs argue that Duke is ultimately responsible for the actions of its scientists and administrators.
“Defendants admit that Dr. Potti fabricated, falsified and intentionally manipulated the data that formed the ‘basis for clinical trials’ in which Juliet Jacobs was enrolled,” one of the plaintiffs’ filings states. “Much of the… falsified, fabricated, and manipulated data came from the laboratory of Dr. Nevins, for which he was ultimately responsible. In fact, Dr. Nevins admitted one set of ‘intentionally altered’ data that came from his lab ‘provided support for the lung cancer trials…’
“Manipulating and fabricating the data for a clinical trial and then lying to a patient to obtain informed consent is a breach of good faith. It constitutes battery and invalidates informed consent. Dr. Potti is the physician who presented the informed consent to the plaintiffs. He is the one who falsified, fabricated and intentionally manipulated the data. He entered into a Consent Order with the North Carolina Medical Board admitting that he committed ‘unprofessional conduct.’ He admitted that there was a responsibility to tell the patients, including Juliet Jacobs, about the controversy with the medicine. Dr. Potti did not inform the Jacobs of either the ‘controversy’ or the fraud.”
Nevins acknowledges that he did not examine the data until October 2010, three months after this publication reported that Potti had misstated his credentials, claiming to have been a Rhodes Scholar, and after Potti was barred from Duke campus.
“Money, Fame and Overall Fortune”
Countering Duke’s assertion that no one was injured because patients were assigned to standard therapy, the plaintiffs say that Juliet Jacobs was falsely led to accept a treatment regimen she would not have ordinarily considered.
The patient’s husband and daughter “testified to the exact opposite,” the filing reads. “Plaintiffs showed that Juliet and Walter Jacobs did not want standard of care chemotherapy and would not have participated if it had not been for the defendants’ fraud.”
The Duke protocol required a second biopsy and led the patient to a chemotherapy regimen that was more aggressive than she would have ordinarily chosen for end-of-life care.
“The second biopsy was not required for the alleged ‘standard of care’ chemotherapy—it was required for participation in the clinical trials,” the plaintiffs argue. “Defendants want to turn a lawsuit based upon personal injury into a wrongful death action. The question is not whether ‘standard of care chemotherapy’ was provided and whether or not the same caused her death. Instead, the question posed by the plaintiffs is whether or not the defendants’ actions caused a personal injury to Juliet and Walter Jacobs. Attempting to recast this as a wrongful death action…is a red herring thrown to distract the finder of fact.”
Most importantly, Juliet Jacobs was deceived, the plaintiffs’ attorneys argue.
“Because her quality of life was very important to her, if she had been given proper consent and told that there was no ‘silver bullet’ and if she had not been told by Dr. Potti that he could give her a chance to live for ten years, she and Walter would more likely than not have made other choices regarding how they spent her last days and what quality that life would have.”
An audio recording of the Jacobs meeting with Potti captures the doctors expressing hope for a miracle.
In the recording, Juliet Jacobs says that her son-in-law has had chemotherapy for a decade, and that he is the only survivor in a clinical trial.
Potti: “Wow. And I, I wouldn’t be surprised if I expect that from you. That’s what I mean. I’m 100 percent on board here, OK?”
Like other patients, Jacobs was presented with a consent form that contained the claim that the genomic predictor that would be used had the accuracy of approximately 80 percent.
Instead of going into hospice care, Juliet Jacobs ended up with a lot of toxicity and a quality of life her family members described as poor.
The date of the family’s meeting with Potti is important: Feb. 11, 2010, a month after Duke restarted the trials following an internal investigation that has since been shown to be cursory and skewed. That controversy was never mentioned to the prospective patient and her family.
Knowing what he knows now, Walter Jacobs is furious.
“I know that it’s an immoral, evil, awful thing that has been done,” he said in a deposition.
The plaintiffs also allege a “civil conspiracy.”
“The underlying conspiracy was among the defendants and Dr. Potti and Dr. Nevins, on behalf of themselves and on behalf of their outside financial interest, Cancer Guide, to cover up the falsification in order to continue the clinical trials. The successful conclusion of the clinical trials would have meant money, fame and overall fortune.”