Search words Anil Potti Duke University
Fact Checker here. Explosive material. Please read.
In November, 2009, as Duke began its first formal investigation into the cancer research of Dr Anil Potti, two Vice Deans of the Medical School -- Drs. Kornbluth and Cuffe -- received a startling e-mail.
A researcher at the renowned M D Anderson Comprehensive Cancer Center at the University of Texas, Keith Baggerly, Ph.D., a statistician, was offering proof that Potti's science was defective if not faked. In other words, blowing one of the stars of Duke Medicine right out of the water.
But neither Kornbluth nor Cuffe passed Baggerly's material along to the investigators.
Instead, they -- or people they did give it to -- concealed it.
FC posted the initial, skimpy information on this most ominous development late last week. Chancellor Victor Dzau told FC in an unusual exchange of e-mails on Saturday that Kornbluth and Cuffe did not act alone, but with others in making this decision. Because of travel problems caused by the snowstorm that closed the Atlanta airport, FC has been unable so far to follow this up -- to get names of those involved said by the website Nature.com to be in the "leadership" of Duke.
We are confident we can get those names from Dzau, who has pledged transparency and kept his word. We have continued confidence in him.
Every Dukie has a stake in this: to hold officials accountable for a horrendous decision and to take steps to insure it does not recur.
✔✔✔ So far, the explanation offered by Kornbluth and Cuffe for concealing Baggerly’s documentation smells, to put it bluntly. They contend if they had sent Baggerly's documentation to the investigators -- who worked under Duke's Institutional Review Board -- the probe would have been "biased."
They offer no evidence much less proof that this would have been the case.
In fact, a strong case can be built that the Review Board -- with carefully crafted established procedures and a panel made up of distinguished MD's and Ph.D's from the ranks of our faculty -- would have given a fair reading to Baggerly‘s material.
✔✔✔ Some critics also point out, that in addition to concealing the Baggerly material, administrators limited the role of the Review Board to answering just two questions. Unfortunately both missed the heart of the matter: that Potti’s starting point of 59 samples of ovarian cancer was flawed.
Or what was supposed to be ovarian cancer.
In asking that a medical journal article be withdrawn, Potti’s mentor, Dr. Joseph Nevins, revealed 16 of those samples are not this kind of cancer at all. Nevins: "At this point, I cannot trace the origin or nature of these samples."
Of the remaining 43 samples, the news is not much better. "The tumor ID labels for these samples are incorrect. In a large number of these cases, the mis-identification results in reversal of the clinical annotation of response vs. non-response." In other words, chemotherapy that helped a patient was recorded as not helping, and chemotherapy that did no good was recorded as helping. Oh lord.
With discrepancies of this magnitude, FC thinks it is an uphill battle to establish there was no willful misconduct. Even so, a key source says "I have not seen a smoking gun."
✔ Kornbluth has said on this issue, that the limitation to two questions occurred because no one thought they had to "dig down" to the first stages of the research.
More smell. This is like having an investigation into the Leaning Tower of Pisa, checking only the 4th, 6th and 8th floors, and neglecting the foundation.
✔✔✔The mystery surrounding motive for this lack of an enthusiastic pursuit of a Potti investigation has caused great concern in the past few days.
-- Some point to the potential dollar value of Potti's "discoveries" if they had panned out. Right now cancer patients are treated with chemotherapy that may or may not work. Often their chemotherapy is switched, so they must start all over again with powerful drugs that are very debilitating even if they do arrest cancer.
Potti's genome researched promised to tell doctors which chemotherapy would work best for each individual patient and against each type of cancer -- information which he said was locked in patterns of DNA and RNA. Of course the doctors would have to send their patients for testing first -- and Duke, Potti et al would hold the patent.
Three grants were being used -- from the federal government and the American Cancer Society -- to address breast, lung and ovarian cancer. But Potti and his mentor, Dr. Joseph Nevins, along with Duke itself , and apparently outside investors, formed a corporation to capitalize on this research, to receive far more than a couple million dollars in research grants.
One expert interviewed by FC said that if the research had panned out, Duke would be sitting top a gold mine: more 700,000 tests a year in the US alone. The expert estimated -- based upon other tests for breast cancer -- that each would cost $1,000.
That's three quarters of a BILLION dollars right there. Not to mention the prospect for medicine's highest honors, the Lasker and the Nobel, for a break-thru discovery of historic proportions.
Indeed, the appearance or prospect that investigations could be swayed caused Dzau -- at a later date -- to order Duke to divest itself of all holdings in the Potti-Nevins enterprise. By then, of course, with challenges to their science, the value was nil.
FC inquired about this, writing Dr. Rose Ritts, executive director of the Health System’s Office of Licensing and Ventures, as well as Michael Schoenfeld, VP for university PR. Neither acknowledged nor answered -- and that in our opinion gives a chancellor who has promised to be open and transparent about this mess reason to speak to them in no uncertain terms.
✔ Beyond the money angle, there is something even uglier. Like the money angle, there is no hint that this scenario played out, but we share it with Loyal Readers because it surfaces time and time again.
Kornbluth and Cuffe were promoted to their current positions by Dean Nancy Andrews of the Medical School. They report to her.
Her husband is Dr. Bernard Mathey-Prevot, co-author with Potti of at least one of his scholarly papers. In other words, the spreading investigation into Potti was bound to knock at his door. At the door of the husband of Kornbluth's and Cuffe's boss.
As FC has written before, there is at least the appearance of a potential conflict of interest in having Kornbluth and Cuffe involved in the heart of the Potti Mess -- and making official statements for the University. We repeat: there is no scintilla of evidence that they did anything wrong. But appearances and possibilities and potential must play a role here.
✔✔✔ By January, 2010 -- a remarkably quick two months given the extreme complexity of the science involved -- Duke’s Institutional Review Board gave rousing endorsement to Potti’s work -- and Kornbluth and Cuffe allowed more patients to enter Potti’s trials.
✔✔✔ Question: when the Vice Deans Kornbluth and Cuffe received the board’s report -- knowing of the Baggerly material -- why at that point didn’t they remand the report for further consideration?
Instead, Kornbluth and Cuffe signed off on the report.
✔✔✔ Duke has refused to tell us who was on the board that cleared Potti -- much less release the report. Duke has variously cited its own policies and federal research rules -- every explanation occluded. The report became part of the public record and subject to a Freedom of Information Request from The Cancer Letter (and more recently, Nature.com got a version without heavy redaction) when it was filed with the federal agencies that were supporting Potti’s research.
--- the approaches (being used by Potti et al)... "are viable and likely to succeed.”
--- "...scientifically valid and with a few additions can be fully responsive to the comments of Drs. Baggerly and Coombes." (the intrepid MD Anderson researchers in Houston)
--- Also in the report: "We can understand some of the (Baggerly-Coombes) misgivings about the application of the methods in actual clinical trials. We think that many of the issues are due to poor and strained communications among the groups..... "
--- And most importantly reassurance for patients already receiving Potti-determined treatment and more about to be enrolled: Use of the Potti science "does not endanger patients."
A Who’s Who in the world of genome research has challenged that.
Is Duke backing away? We are reviewing one recent Duke paper that suggests the University realizes it’s a no-win hard-line view to maintain no patient was harmed.
In part Duke apparently bases its hard-line position on the theory that the patients who got a specific chemotherapy directed by Potti are no worse off than they would have been had they started a routine hit-or-miss treatment.
Well, not really. This neglects that Potti kept patients on the chemotherapy he dictated -- not switching them to new therapies when the first did not work.
And it neglects that with some lung cancer patients, Potti used a drug cocktail -- a mixture of chemotherapy that he himself apparently concocted that is not authorized for use by regulators. This little ditty is just emerging.
✔ We believe the November 2009, Institutional Review Board was chaired by Dr. John Harrelson, retired professor of orthopedic surgery and associate professor of pathology, Trinity '61 and MD '64.
He wrote an E-mail on January 7, 2010, to the National Institutes of Health. Of course Fact Checker has seen it: "Based upon the review process, we believe that the trials are safe for patients, the scientific basis for these studies is valid and we have every reason to hope that important results will be obtained. In light of these reviews, we are initiating processes to re-open enrollment in the involved trials."
✔✔✔ The renewal of the clinical trials set off a howl in early 2010. But it was the discovery of a faked Rhodes Scholarship in Potti’s resume in June that the media could understand. After The Cancel Letter revelation, world-wide headlines sullied Duke’s image.
This was followed by suspension of Potti’s trials for existing patients as well as new, by a declaration by Nevins that a paper he co-authored had no validity whatsoever, and by Potti’s resignation.
From Baggerly: a prediction that there not be a "charitable explanation" for any of this.
FC can only offer these words: to be continued.
✔✔✔✔✔ There are now two investigations into the Potti Mess underway. What is most alarming is that FC cannot assure Loyal Readers that either will touch upon the administrative mis-steps detailed above.
In fact, the Institute of Medicine is being directed away from Potti toward a fuzzy, general inquiry into standards for genome research in general. This may be important to address -- but not at the expense of learning what enabled Potti to get away with his fraud for so long.
And Duke has another round underway with its Institutional Review Board, this time formal faculty misconduct charges.
But who is under investigation? Just Potti? Nevins? Or any of the others in the vortex and on the fringes of this scandal.
Your guess is as good as ours, so if you get a whiff of any new odor, write Duke.Fact.Checker@gmail.com.
Thank you for reading Fact Checker.