Trial in Medical Research Scandal Postponed
By Jay Price
DURHAM, N.C. — A judge in Durham County Superior Court has postponed the first civil trial against Duke University by the estate of a patient who had enrolled in one of a trio of clinical cancer studies that were based on bogus science.
The case is part of what the investigative TV news show “60 Minutes” said could go down in history as one of the biggest medical research frauds ever.
The trial had been scheduled to start Monday, but several attorneys involved contracted flu. Judge Robert C. Ervin hasn’t settled on a new start date, but after a conference call with him Monday night, attorneys in the case said it could be as late as this fall.
Flu? Don’t these lawyers get flu shots? Wasn’t Duke working on a flu vaccine? Delaying til Fall 2015?
The postponement delayed resolution in the long-running case for the two patients still alive among the eight who filed suit. It also prolonged a lengthy public relations headache for Duke Medicine that has included retraction of research papers in major scientific journals, the embarrassing segment on “60 Minutes” and the revelation that the lead scientist had falsely claimed to be a Rhodes Scholar in grant applications and credentials.
Because it’s not considered a class action, the eight cases may be tried individually. The one designated to come first was brought by Walter Jacobs, whose wife, Julie, had enrolled in an advanced stage lung cancer study based on the bad research. She died in 2010.
“We regret that our trial couldn’t go forward on the scheduled date,” said Raleigh attorney Thomas Henson, who is representing Jacobs. “As our filed complaint shows, this case goes straight to the basic rights of human research subjects in clinical trials, and we look forward to having those issues at the forefront of the discussion when we are able to have our trial rescheduled.”
It all began in 2006 with research led by a young Duke researcher named Anil Potti. He claimed to have found genetic markers in tumors that could predict which cancer patients might respond well to what form of cancer therapy. The discovery, which one senior Duke administrator later said would have been a sort of Holy Grail of cancer research if it had been accurate, electrified other scientists in the field.
Then, starting in 2007, came the three clinical trials aimed at testing the approach. These enrolled more than 100 lung and breast cancer patients, and were eventually expected to enroll hundreds more.
Duke shut them down permanently in 2010 after finding serious problems with Potti’s science.
Now some of the patients – or their estates, since many have died from their illnesses – are suing Duke, Potti, his mentor and research collaborator Dr. Joseph Nevins, and various Duke administrators. The suit alleges, among other things, that they had engaged in a systematic plan to commercially develop cancer tests worth billions of dollars while using science that they knew or should have known to be fraudulent.
The latest revelation in the case, based on documents that emerged from the lawsuit and first reported in the Cancer Letter, a newsletter that covers cancer research issues, is that a young researcher working with Potti had alerted university officials to problems with the research data two years before the experiments on the cancer patients were stopped.
The whistleblower, Brad Perez, is now finishing up a medical residency at Duke. Perez declined to be interviewed, but responded by email that the issues with the research led him to quit working with Potti, though that cost him an extra year in medical school.
“In the course of my work in the Potti lab, I discovered what I perceived to be problems in the predictor models that made it difficult for me to continue working in that environment,” he wrote. “I raised my concerns with my laboratory peers, laboratory supervisors and medical school administrators. I chose to take an additional year to complete medical school in order to have a more successful research experience.”
In an emailed statement in response to questions about the case, Michael Schoenfeld, Duke’s vice president for public affairs and government relations, said Perez had passed his concerns about the lab through proper channels at Duke, and that the resulting review didn’t find research misconduct.
Since then, though, Perez’s concerns have been fully appreciated and recognized, Schoenfeld wrote.
“We can say with great confidence that any concerns like this received today would be handled very differently,” Schoenfeld wrote.
Really? What would they do differently?
“Despite his experience in Dr. Potti’s lab, we’re pleased that Dr. Perez elected to complete his medical education and research training at Duke, and is currently completing his residency in radiation oncology at Duke.”
Through his Raleigh attorney, Dan McLamb, Potti declined an interview, citing the pending court action. Potti now works at another cancer clinic, in Grand Forks, N.D.
No surprise he’s still practicing. Remind me of where not to go.
Potti, Nevins and various collaborators published studies in major research journals based on Potti’s findings beginning in 2006. But researchers elsewhere couldn’t reproduce their results and quickly began to raise questions. In particular, two biostatisticians at MD Anderson Cancer Center in Houston, Keith Baggerly and Kevin Coombes, brought problems they found to the attention Duke officials and began questioning the research publicly.
In 2009 Duke suspended the enrollment of new patients and commissioned an outside review. But the reviewers reported that Potti’s work seemed fine, and Duke rebooted the trials. University leaders later said those reviewers hadn’t looked at the basic data Potti had used.
Only after the Cancer Letter, which has followed the case closely for years, published a report in 2010 saying that Potti had falsely claimed a Rhodes Scholarship in grant applications and elsewhere did Duke’s official support for the research finally began to crumble. It again suspended new enrollments and ended the studies.
Outside scientists who raised questions about the research said they were most worried about the prospect that patients were being put at risk by their participation in the clinical trials. They said the unproven genetic analysis could result in patients being prescribed an improper treatment.
The following sounds like doublespeak:
Duke has maintained, though, that the patients received proper care.
“The criticism in the lawsuit is not related to the high quality of care this patient received,” Schoenfeld wrote in his statement. “While the science behind the genomic predictor used in the trials was ultimately found to involve falsified data, a key factor in the approval of the trial protocols provided that every patients would receive standard of care therapy for their disease whether or not the predictor ultimately proved to be useful.”
Firstly, the patients were promised “a personalized cancer regimen”custom-tailored for their tumor; secondly, the last sense is incomprehensible. Second, some of them were apparently getting the less effective treatment due to data mix-ups. Realize that these “treatments” also involved additional surgeries for purposes of the clinical trial only. Please correct me if I’m mistaken.
Regardless of which treatment patients in the clinical trials received, it was considered a best one for treating their disease, he wrote.
“A” best one?
The lawsuit charges, among other things, that in grant applications for the clinical trials that Potti intentionally lied, and included false and fraudulent information about the research results. Nevins, as his research supervisor, and Duke should have known what was wrong, the lawsuit says, because biostatisticians from MD Anderson and others had made numerous attempts to call attention to flaws in the science.
The suit also charges that the clinical trials began after Duke had been “placed on notice” of the flawed underlying science and suggests that the relationships among researchers and administrators were too cozy within the university for it to properly pursue questions about the research.
Duke has made substantive changes to prevent the problems brought to light in the Potti case from recurring, Schoenfeld said. These include better data management, new reviews of potential conflict of interest and improvements in handling reports related to the integrity of research.
“Many lessons learned from this situation have led to significant improvements in both basic and clinical research processes including many new and expanded programs related to scientific accountability, reporting of concerns related to research integrity, multiple improvements in data management and governance, and new scientific and conflict of interest review processes,” he wrote.
Duke put Potti on administrative leave in July 2010 after the charges about his credentials emerged. The next month, Duke announced that he had indeed padded his resume. Potti resigned six months later, and Nevins began the process of retracting the journal articles. Nevins retired from Duke in 2013.
In 2012, Potti accepted a reprimand from the North Carolina Medical Board. He remains licensed to practice in the state and in a few other states. According to records posted online by the North Carolina Medical Board, Potti had agreed to settlements in at least 11 malpractice cases against him, each resulting in a payment of at least $75,000.
Also, in a consent order negotiated with the medical board, Potti agreed to accept a formal reprimand for unprofessional conduct and admitted to having inaccurate information on his resume and in official Duke biographical sketches and to using those flawed credentials in research grant applications.
After leaving Duke, Potti worked awhile in a clinical role rather than in research at a cancer clinic in South Carolina. He was fired from that job after the “60 Minutes” segment aired, though the company he had worked for there, Coastal Cancer Center, said in a news release that his work had been exemplary.
The news release also said that the company had hired him after received glowing letters of recommendation from top medical officials at Duke.
While the trial may be delayed for months, the judge still is expected to hear motions in the case Thursday.
Note: I did not fix any of the ungrammatical parts of this news release.
Read the article here:
For background posts on this blog, please see:
The following is an excerpt from this week’s Cancer Letter on the issue of “No Harm done?”
No Harm Done? 1/23/15
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.
Imagine if she had been told the trials had been stopped on grounds of flawed data/bad models, and only recently renewed. Imagine if she’d seen the Perez letter or the Baggerly and Coombes articles. I can’t argue the legal subtleties, but it’s outrageous.
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.”