publication date: Dec. 4, 2013

Prominent Duke Scientist Claimed Prizes
He Didn’t Win, Including Rhodes Scholarship

By Paul Goldberg

A high-profile cancer genomics researcher at Duke University claimed in multiple grant applications that he had been a Rhodes scholar, when, in fact, the Rhodes Trust states flatly that he was not.

Documents obtained by The Cancer Letter show that in biographies submitted to NIH, Duke oncologist and genomics researcher Anil Potti claimed variously to have won the prestigious scholarship in 1995 or 1996, depending on the version of the biography.

Potti also made the Rhodes claim in an application that resulted in a $729,000 grant from the American Cancer Society.

“We don’t have any record that Anil Potti was a Rhodes scholar,” a spokesman for the Rhodes Trust said to The Cancer Letter.

Questions about Potti’s credentials seem consistent with the trail of errors acknowledged by his prominent and well-funded research group, whose work has been published in top-tier journals, including the New England Journal of Medicine and Nature Medicine.

This body of work has brought in millions of dollars in funding from the federal government and private sources, but has been marred by corrections and even corrections of corrections.

Errors in genomics research could have direct implications for patients. In three clinical trials currently enrolling patients at Duke, Potti and colleagues seek to correlate genomic analysis of tumors with patient outcomes. Recently, NCI told a cooperative group—Cancer and Leukemia Group B—to stop testing a genomic assay based on a Duke technology (The Cancer Letter, May 14, 2010).

In one of his applications for funds, Potti claimed to have been a Rhodes scholar, adding in parentheses “Australia.” In another, he added “Australian Board.”

Biographies submitted to NIH and obtained by The Cancer Letter state that Potti held a “research fellowship” at “Queensland Research Institute” in 1995-1996, the year he claimed to have been a Rhodes scholar.

Since no such institution exists, it’s almost certain that the bio is referring to Queensland Institute of Medical Research. The institution states that he had never worked there.

The Cancer Letter sent an email with questions to Potti, his collaborator Joseph Nevins, and Duke administration officials. The questions focused on the Rhodes claim, but also touched on other apparent discrepancies.

Responding to everyone on the email CC list, including this reporter, Potti wrote: “Sounds like I need to call him to clarify…and probably also talk with you all to clarify. I was a nominee…and several of the others can also be explained. –Anil.”

After that email, Potti and Duke officials didn’t respond to questions seeking details that could substantiate this response. Multiple calls and emails from The Cancer Letter were not acknowledged.

Officials at Rhodes Trust said that applicants— including those weeded out late in the selection process—are not entitled to refer to themselves as Rhodes scholars. “Although thousands of outstanding young women and men apply for a Rhodes scholarship each year, the Rhodes Trust self-evidently expects that an individual will only claim to be a Rhodes scholar after having been formally awarded the scholarship by the trustees,” the spokesman said.

The Oxford-based trust that administers the program doesn’t keep track of all unsuccessful applicants. Rhodes officials said that geographical reality of being in Australia—if he was indeed there—should have alerted Potti to the fact that he was not a Rhodes scholar. “The Rhodes scholarships only apply for study at the University of Oxford,” a spokesman said. “Therefore Anil Potti would not be able to fund study at the Queensland Institute of Medical Research from a Rhodes scholarship.”

Also, officials at the trust said they were unaware of any scholarship that could be reasonably expected to be mistaken for theirs. “The Rhodes scholarships are highly prestigious and we would be concerned if our name was being misused,” the spokesman said. A list of Rhodes scholars is posted at http://www.rhodeshouse.ox.ac.uk/section/rhodes-scholars-complete-list-1903-2009

Potti’s biographies submitted to NIH raise several questions about the oncologist’s whereabouts in 1995 and 1996.

According to these documents, Potti graduated from an Indian medical school—Christian Medical College of Vellore—in 1995. However, officials at the medical college said to The Cancer Letter that he had graduated in 1996.

A third version of events appears in Potti’s application for residency at the University of North Dakota. Documents attached to that application indicate that he received a Vellore medical degree in 1994. The application package, which was obtained by The Cancer Letter, doesn’t mention Rhodes. The documents are available on The Cancer Letter website http://cancerletter.com//categories/documents.

Potti started residency at the University of North Dakota in 1996 and went on to a fellowship at Duke in 2003. It’s not publicly known whether the Rhodes claim was made in Potti’s fellowship application to Duke.

When Potti first came to Duke, he was widely believed to have been a Rhodes scholar, sources said.

This common belief is reflected in a January 2007 newsletter published by the Duke Institute of Genome Sciences and Policy. The story about Potti joining the institute identifies him unambiguously as a “Rhodes Scholar.” A copy of the article is posted on The Cancer Letter website http://cancerletter.com//categories/documents.

There is no indication that either Potti or Duke officials corrected the record.

Rhodes Claim Strengthened ACS Application

Responding to an inquiry from The Cancer Letter, the American Cancer Society confirmed that Potti’s application for a funded grant mentioned Rhodes.

“Dr. Anil Potti did apply for a mentored scientist award, which was funded. He submitted a curriculum vitae with his application that indicated he was a Rhodes (Australia) recipient,” said an ACS spokesman.

According to materials on the ACS web site, the Rhodes credential could have been reasonably expected to give Potti an edge to obtain the highly competitive award. His $729,000 award, categorized as a “mentored research scholar grant in applied and clinical research,” started in July 2007 and runs through 2012.

ACS is financing Potti’s research under mentorship of collaborator Nevins, the Barbara Levine Professor of Breast Cancer Genomics and director of the Center for Applied Genomics & Technology, a component of the Institute for Genome Sciences and Policy.

The research is focused on tailoring lung cancer therapies to individual patients. An abstract describing Potti’s ACS grant is posted at http://www.cancerportfolio.com/abstract.jsp?SID=224124&ProjectID=484163.

Evaluation of credentials of both the applicant and the mentor are among criteria ACS uses in awarding such grants. These criteria are posted on the society’s website:

• Applicant: Their academic and scientific qualifications, potential to succeed as an independent investigator, and commitment to research as a career.

• Mentor: The appropriateness of the mentor’s research qualifications in the proposed project area, the role of the mentor on the project, research productivity and prior success in fostering the development of cancer researchers.

The mentor is required to prepare a section of the application.

 

Rhodes Claim Vanishes

A Rhodes scholarship is not the sort of credential that drops off a CV even when former scholars go on to become Nobel laureates or heads of state. Yet, the scholarship vanishes from Potti’s biographies sometime in 2007.

A “biographical sketch” filed as part of an NCI grant that was ultimately funded (R01-CA116648- 01A1) described Potti as a “1995 Rhodes Scholar (Australia).” The document doesn’t mention the research fellowship in Queensland. The grant runs from Aug. 21, 2006 through July 31, 2010. The biography was obtained under the Freedom of Information Act.

Another brief bio, submitted as part of an unsuccessful application to the National Heart, Lung and Blood Institute, described Potti as a “1996 Rhodes Scholar (Australian Board).”

The Rhodes credential then disappears from a later bio, submitted as part of an NCI training grant that lists Potti as a member of the faculty who would provide training for young neurosurgeons. In that version of the bio, Potti states that in 1995 and 1996 he was a research fellow in Queensland.

Also, for the first time, Potti states that in 1995 he was a “National Merit Scholar.” (In another bio, he claims to have been a National Merit Scholar in 1989.) Such scholarships are sponsored by various local and central government agencies and are difficult to verify.

Neither the Rhodes nor the National Merit Scholar claims appear as part of Potti’s official profiles on Duke websites.

The three biographical sketches that were submitted to NIH are posted on The Cancer Letter website http://cancerletter.com//categories/documents.

The entire neurosurgery application is posted at http://www.duke.edu/web/surgery/neurosurgery/FINAL%20R25%20grant%2020080910.pdf.


Dreams of Australia

Potti’s account of his experience in Australia is remarkably detailed.

A recent biography submitted to NIH reads: “1995-1996 Research Fellowship at Queensland Research Institute, Australia (Mentor: Gordon McLaren).”

In another bio, he describes this fellowship as part of his 1996 Rhodes scholarship and cites his research project as an inquiry into “cardiac effects of beta-thalassemia/HgbE in southeast Asians.”

If Potti was ever a research fellow at Queensland, the institution is not aware of this. “QIMR has no records of a person name Dr. Anil Potti ever having worked at the Institute,” Trevor Greenway, human resources manager, said in an email.

Reached by The Cancer Letter, McLaren said he was “shocked,” “saddened” and “flabbergasted” to hear that Potti described him as his mentor in Australia.

McLaren indeed spent a six-month sabbatical Queensland, from December 1994 through June 1995. However, he didn’t know Potti at that time.

“This is really strange,” McLaren said after a reporter told him about claims on government documents submitted by Potti. “I was there by myself, except for my wife.”

McLaren said he met Potti in 1996, in Fargo, North Dakota. At the time Potti was a resident in internal medicine and McLaren chief of hematology and oncology section of the VA.

“He would have been aware of my having been on a sabbatical at Queensland,” said McLaren, who is now a professor at the University of California, Irvine, and an oncologist in the VA Long Beach Healthcare System.

In Australia, McLaren didn’t study the cardiac effects of beta-thalassemia/HgbE in southeast Asians. However, in Fargo he helped Potti prepare a poster on this subject.

“I helped him write it up for an abstract, so he could submit it for a poster competition for the American College of Physicians,” McLaren recalled. Potti already had the data, which he brought with him from India, McLaren said.

The Rhodes story sounds familiar, too, McLaren said. “What I remember hearing about the Rhodes scholarship is that he had been awarded it, but about the same time he got into the residency program in North Dakota, and he was sort of hoping that they would hold the place for him,” he said. “It seems to me he said he was supposed to do the Rhodes someplace in Australia, and the latest I remember is they couldn’t hold it for him, so he ended up not doing the Rhodes.

According to copies of documents supporting his application to the University of North Dakota, Potti was in India at the time he said he was in Queensland. Documents show that from June 1, 1995, through April 1, 1996, he was a resident at University of Medical Sciences and Guru Teg Bahadur Hospital in New Delhi.

North Dakota appears to be his second residency, a fact not reflected in any of his bios.


1998 ASCO Merit & Travel Awards?

The Cancer Letter was unable to verify two less prestigious awards listed by Potti.

All three biographies submitted to NIH and obtained by The Cancer Letter state that in 2001 Potti won awards from the “Cure for Lymphoma & Lymphoma Research Foundation.” The honor is cited as “Junior Faculty Award” in one application and simply as an “Award” in the other two.

“In 2001, two organizations merged to create the Lymphoma Research Foundation and grant records from that transition period do not show that the Foundation awarded a grant to someone by that name,” said a spokesman for Lymphoma Research Foundation.

One of his bios states that in 1998 he won a “Travel Award” from the American Society of Clinical Oncology. Two other versions state that he won the ASCO “Merit Award” during the same year. There is no record of Potti receiving either a merit or a travel award at the 1998 ASCO annual meeting, society officials said. “Dr. Anil Potti is a one-time recipient of ASCO’s Travel Award and Merit Award,” a spokesman said. “In 2005, he received the Travel Award and in 2006, he was given the Merit Award for his abstract, ‘A genomic strategy to combinatorial therapeutics in solid tumors.’”

Geoffrey Mearns, interim provost of Cleveland State University and a former federal prosecutor, said that “anyone who submitted a false statement to a federal agency in connection with grant funding has potentially violated a federal statute.” Title 18 of U.S. Code, Section 1001 makes it a federal crime to make a false statement to the government, said Mearns, who handled prosecution of organized crime figures at the Eastern District of New York and later prosecuted one of the men convicted in the bombing of the federal building in Oklahoma City.

“He would have been aware of my having been on a sabbatical at Queensland,” said McLaren, who is now a professor at the University of California, Irvine, and an oncologist in the VA Long Beach Healthcare System.

In Australia, McLaren didn’t study the cardiac effects of beta-thalassemia/HgbE in southeast Asians. However, in Fargo he helped Potti prepare a poster on this subject.

“I helped him write it up for an abstract, so he could submit it for a poster competition for the American College of Physicians,” McLaren recalled. Potti already had the data, which he brought with him from India, McLaren said.

The Rhodes story sounds familiar, too, McLaren said. “What I remember hearing about the Rhodes scholarship is that he had been awarded it, but about the same time he got into the residency program in North Dakota, and he was sort of hoping that they would hold

Another class of statutes, where the victim is not the government, can also come into play in cases where credentials are misstated. “If that statement was transmitted using the mails or if it was transmitted in a wire interstate, then that can be wire fraud or mail fraud,” Mearns said.

Federal prosecutors look for a pattern of false statements before they select a case for prosecution. “Generally speaking, federal prosecutors are going to be reluctant to get themselves involved in what may appear to be either a civil dispute or a research or administrative matter,” Mearns said. “But if they were convinced that there is a broad pattern of deception, they might be more inclined to conduct an investigation.”

The North Carolina Medical Board has the authority to discipline physicians for “unprofessional, immoral, or dishonorable conduct,” or “crimes of moral turpitude.”


Duke Defended Potti’s Science, Clinical Trials

Duke University’s administration has been supportive of Potti and Nevins throughout the controversy over their scientific findings.

Genomic research led by the two scientists has brought millions of public and private dollars to Duke. The duo’s connections with the industry are considerable. According to a recent disclosure, Potti is a member of the scientific advisory boards of Eli Lilly and Co., GlaxoSmith-Kline, and CancerGuideDx.

Nevins has been a member of the scientific advisory boards of Johnson & Johnson, Millennium Pharmaceuticals, CancerGuideDx, and the Erbitux Biomarker Advisory Board of Bristol-Myers Squibb. He holds equity in Expression Analysis Inc.

Both Nevins and Potti are listed on Duke-held patent applications describing “methods for using genomic signatures to predict oncogenic pathway activation and for predicting chemotherapy sensitivity.”

Though many scientists doubt the group’s findings and question appropriateness of clinical trials based on their technology, Duke uses Potti and his message of “personalized medicine” to draw patients to the center. The commercials are posted at http://www.youtube. com/watch?v=diWKtw0yQ7I&feature=channel. Potti’s photos also figure on the center’s brochures.

The Nevins and Potti team emerged as pioneers of personalized medicine in 2006, when Nature Medicine published their paper claiming that microarray analysis of patient tumors could be used to predict response to chemotherapy.

However, two biostatisticians at the MD Anderson

Cancer Center attempted to verify this work when oncologists asked whether microarray analysis could be used in the clinic. Keith Baggerly and Kevin Coombes, the statisticians, found a series of errors, including mislabeling and an “off-by-one” error, where gene probe identifiers were mismatched with the names of genes.

Baggerly and Coombes said they devoted about 1,500 hours to checking Potti’s and Nevins’s work. These efforts—dubbed “forensic bioinformatics”— resulted in a paper in the November 2009, issue of the Annals of Applied Statistics.

“Unfortunately, poor documentation can shift from an inconvenience to an active danger when it obscures not just methods but errors,” the paper stated. “Patients in clinical trials are currently being allocated to treatment arms on the basis of these results.”

The two raised questions about Duke’s randomized phase II single-institution trials that used the Nevins and Potti technology to assign patients to treatment (NCT00545948, NCT00509366, and NCT00636441). Baggerly and Coombes argued that these trials “may be putting patients at risk.”

After publication of this paper, Duke suspended the three trials, one of which (NCT00636441) was co- sponsored by the Department of Defense (The Cancer Letter, Oct 2, Oct. 9, Oct. 23, 2009). It’s not publicly known whether Potti’s biography submitted to DOD listed the Rhodes credential. A FOIA request for the application is pending.

The university’s internal investigation at the time included a review of the scientific underpinnings of the trials. Duke’s Institutional Review Board turned to three directors of cancer centers and a separate, independent panel of biostatisticians. Sources said three biostatisticians were involved.

Citing recommendations of these panels, Duke officials restarted the trials. This was announced in a statement signed by two Duke deans, who declared that “an examination of the underlying scientific methodology that had been published by the Duke investigators, and used in these trials, was confirmed by reviewers’ own independent analysis using the respective datasets and prescribed methods of analysis,” which led the reviewers to conclude that “the approaches used by the Duke clinical predictors are viable and likely to succeed.”

The statement was signed by Michael Cuffe, vice dean, medical affairs, at Duke University School of Medicine, and Sally Kornbluth, vice dean for research (The Cancer Letter, Jan. 29).

However, some very important information remained shielded from public view at the time Duke made its announcement. First, the text of the report prepared by outside scientists was not released. “While the reviewers approved of our sharing the report with the NCI, we consider it a confidential document,” Cuffe said to The Cancer Letter at the time.

Also, Duke never identified any of the outside experts who were consulted.

Duke officials apparently didn’t realize that sharing the report with NCI was inconsistent with their intent to keep it confidential.

Once the report made its way into the institute’s hard drives and file cabinets, it became subject to provisions of the Freedom of Information Act, and was obtained by The Cancer Letter.

The report and a related document are posted on The Cancer Letter website http://cancerletter.com//categories/documents.

The documents were redacted to eliminate the names of individuals involved in Duke’s investigation and to protect trade secrets and patentable data.

Experts asked by The Cancer Letter to review these documents noted that Duke deans Cuffe and Kornbluth were inaccurate in their description of the document’s substance and conclusions when they announced completion of the investigation and resumption of the clinical trials earlier this year.

“Having read the committee’s report, we must disagree with Duke’s representation of the committee’s findings,” Baggerly and Coombes said in an email after reviewing the documents released under FOIA. The committee stated that “In our review of the methods … we were unable to identify a place where the statistical methods were described in sufficient detail to independently replicate the findings of the papers,” and further noted that the Duke investigators “really need” to work on “clearly explaining the specific statistical steps used in developing the predictors and the prospective sample assignments.

“Duke’s statement implies other members of the scientific community should be able to replicate the reported results with the data available,” Baggerly and Coombes said. “Having tried, we can confidently state that this is not yet true.”

In another setback to the Duke group, NCI last May eliminated a biomarker test from an ongoing phase III clinical trial.

The decision by the NCI Cancer Therapy Evaluation Program last May to remove the Lung Metagene Score (LMS) assay from the trial conducted by the Cancer and Leukemia Group B challenges a Duke technology that has not previously attracted scrutiny.

NCI officials said the assay was eliminated because the institute was “unable to confirm the score’s utility.”

The decision eliminated the assay from the 1,525-patient trial of adjuvant chemotherapy in non-small-cell lung cancer was based on a biostatistical review that was prompted in part by problems in other aspects of work by the Duke group.

The LMS is a prognostic model that was being tested for its ability to identify non-small-cell lung cancer patients who may be at high risk of recurrence.

The assay is different from the previously questioned work by Duke scientists. While earlier assays were used to predict sensitivity to chemotherapy, the function of the LMS was to gauge the risk of disease recurrence.

 

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