Search words Anil Potti Duke University
✔ Fact Checker here. Fellow Dukies, good day.
FC's essay today has substantial focus on Potti's patients. We also review Duke's leadership during this scandal, focus on Potti's co-workers as well as the doctor himself, and finally turn to the intrepid researchers Keith Baggerly and Kevin Coombes at the renowned MD Anderson Comprehensive Care Center in Houston, and The Cancer Letter and its editor, Paul Goldberg '81.
FC does not give out accolades often. Nor without grand reason.
This morning we express complete confidence in the leadership of our medical enterprise, and the sincerity of efforts to understand the way the Potti mess unfolded and to insure it cannot repeat itself. Here or anywhere else.
Both Chancellor Dzau and Huntington Willard, director of the Duke Institute for Genome Sciences and Policy, have been fully responsive to our many questions -- many questions -- and most generous -- unexpectedly generous and immediate -- with their time in providing answers. Moreover, we believe the answers are candid and comprehensive.
This doesn't mean FC always agrees with the Chancellor and Director, nor certainly Dzau and Willard with FC; but we think it fair to say that all share the philosophy that reasonable people can disagree.
Nor does our confidence mean we will not raise new questions based on new evidence and perspectives, as we do today: whether there is any conflict of interest, potential conflict, perceived conflict or possibly a perceived potential conflict in one of the most fundamental decisions -- to invite the Institute of Medicine to conduct an unfettered inquiry. This review will begin in January. See below.
This is an important caveat: Loyal Readers should not assume that unattributed information in our reports comes from official sources. Fact Checker is deluged with tips. In fact yesterday (Sunday) Willard marveled how quickly FC posted his internal memo on Friday announcing Potti's resignation, correctly concluding we have a mole within his organization.
At the risk of yelping from Continuous Carpers (new sub-set of Loyal Readers being recognized today for the first time), we add that FC does not have a favorable view of President Brodhead's handling of one of the great crises of his tenure (yes, along with lacrosse and the financial meltdown).
We do not find that Uncle Dick has taken any profile at all, that is to say exhibited any leadership. In particular, he has not expressed appropriate concern for the patients.
His only important comment came just after The Cancer Letter reported Potti's fake claim of a Rhodes Scholarship and the Rhodes Trust confirmed there was no award. With other credential issues looming at the time, Brodhead cautioned the editorial board of the Herald-Sun not to reach rapid conclusions of truth or lie, for there could also be "intermediate explanation."
Pathetic. Dick, just pathetic.
✔✔ THE PATIENTS
While different numbers have surfaced, we believe 1,518 people came to Duke in desperation, people with life-threatening cancers, people grasping for hope who were channeled to Potti's office for review for possible inclusion in his clinical trials -- which is to say human experiments employing his theories that DNA and RNA -- the human genome -- contained information on how to fight specific cancers.
We do not know how many patients were accepted. We do know 109 people were in the trials at the point last winter when Duke, questioning Potti's science, suspended new enrollments for several months, a decision that did not affect the 109.
As Loyal Readers know, Duke subsequently re-opened enrollment after an internal review turned out glowing. We do not know how many more joined at that point.
All of these people signed "informed consent" forms -- meaning they were fully briefed on the experiments and the chances. What they expected, however, was a good faith experiment, not bunk. Not bunk within the walls of a university medical center that had plenty of warning Potti's science held no water.
Even the people who were merely screened were deeply affected. It is our understanding that many underwent painful, sometimes dangerous procedures to get tissue from lung and ovarian cancers for analysis.
At least 109 were given specific chemotherapy based upon Potti's "discovery" of what would work; they gave up other possible treatments.
Duke maintains they were not harmed. We believe this is a very cynical approach derived from the following: before Potti claimed otherwise, no one knew what therapy would work best against an individual's cancer -- or if it would work at all. It was hit or miss. So Duke figures that everyone in the Potti trials could have been given the precise chemotherapy Potti gave them, and thus the patients are not any worse off for his phony science.
Worse off physically that is; no one is speaking of the stress and mental turmoil that would occur when you learn your cancer doc is a quack.
That's our interpretation; we await confirmation.
We have heard no one outside the boundaries of this campus who is speaking up to say the patients were not harmed.
The Cancer Letter -- which has broken most of the news in the Potti scandal -- turned to Dr. George Sledge, the President of the American Society of Clinical Oncology, a professor at Indiana University, for interpretation. "It is safe to assume that patients might have been assigned to treatments that were unlikely to benefit them and possibly even to harm them."
And Dr. David Carbone, chair of cancer research at Vanderbilt: because of errors in Potti's research, "you may be withholding an effective treatment from some people or giving an ineffective targeted drug" suggested by the research. And "there is the possibility of patient harm."
From Dr.John Ruckdeschel, director and CEO of the Nevada Cancer Institute: "The potential for patients to have been treated differently than they might have otherwise been is present."
My fellow Dukies, one person who writes FC all the time, often with funny flippant information, says he has chartered a bus to bring plaintiffs' lawyers to Duke.
FC is concerned because Duke has developed a reputation for being pretty nasty in litigation. Yes lacrosse, but let's look beyond.
Six years ago, two hospitals run by Duke -- not on campus -- negligently used recycled hydraulic fluid from elevator maintenance to sterilize surgical instruments, rather than a special detergent. This went on for months with 3,648 patients exposed. Oh yes, it went on despite surgeons who kept on saying their instruments felt greasy and slippery.
Ronald Buchanan was operated on during this period -- but for five years Duke would not tell him if he was one of the endangered patients. Five years. Finally, mindful of the statute of limitations, he sued.
Earlier this near, Duke provided evidence that Buchanan had not been exposed to the hydraulic fluid and won dismissal of his lawsuit.
And guess what. Vindictive Duke is now suing Buchanan trying to recover the university's legal costs. This is a disgrace; general counsel Pamela Bernard should be ashamed of this tactic.
Fellow Dukies, we should not tolerate any of this with the cancer patients. Duke must own up to its responsibilities for malpractice.
We will be watching to see if Duke salts away any money to pay these plaintiffs, for we believe hundreds of millions of dollars are ultimately at risk. We note that some of Duke's insurance is handled through a corporation Duke created called Durham Casualty Company. The casualties are malpractice victims, and all this is not in Durham at all, but a corporation founded on an island in the deep Caribbean and most recently moved to Bermuda to shield all from prying eyes.
This university should be better than that; it should be transparent and accountable.
Next step: FC is requesting copies of the letter that Duke sent to all patients, advising them of this mess.
✔✔ ANIL POTTI, MD
A FC friend called. He said Potti is done. I replied there is a lot of redemption in the world. Last week I watched former President George W. Bush, pushing his new autobiography on the Tonight Show, talk about his being a worthless drunk until age 40. (Please, no nasty political comments). Right now as I write, I am half-watching the Giants - Eagles game, where the resurgent Michael Vick has just scored a touchdown.
On the other side, a highly placed administrator told us flatly, his career is "not recoverable" no matter how continuing investigations turn out.
Fact Checker has learned from three sources that since the scandal began, Potti has been largely isolated in his Chapel Hill home but in regular contact with two people, including one Duke colleague with whom he had developed a particularly close friendship. Their contacts started on the phone. The format changed to in-person conversations when Potti's co-author Joseph Nevins renounced their work and asked the Journal of Clinical Oncology to retract an article dealing with ovarian cancer.
There were several long face to face meetings, the theme to keep Potti realistic about his options.
Then last Monday, a new dimension: Nevins wrote Potti an e-mail informing him he was asking the journal Nature Medicine to retract a second article. Potti apparently -- not confirmed -- agreed to join in requesting the retraction; it is not known at all whether he joined in the first retraction from the Journal of Clinical Oncology (JNO). It is customary for all authors of a article to ask for retractions, rare as they are.
With the gathering storm, on Wednesday Potti took his conversations with his one-time colleague and one other contact to a new level -- asking what to do. He was counseled to resign immediately -- before even more bad news came out. Indeed, Nevins was already looking beyond the two papers into more joint publications with Potti; Nevins' on-line resume, obviously out of date, lists eight such papers in the 2006-08 period alone.
Loyal Readers will recall our report months ago that Potti was getting the same advice from several Duke colleagues who met with him. This time he agreed.
On Thursday afternoon lawyers became involved, and Thursday night the murmur was Potti had signed papers. Friday morning the documents reached the Chancellor's office. By early afternoon, Duke made the announcement that made headlines around the world. Literally. Embracing an elite university, this is one of the largest scientific scandals imaginable.
There was a surprise element in the announcement on Friday that very few knew about. Five days earlier Duke had quietly called it quits on all of Potti's experiments and got the patients to other doctors.
One source in an excellent position to know full details says at no time was Potti pushed to resign from Duke.
What we do not know is the terms of his leaving: whether Potti asked for or was given any financial incentive. Our sources -- at least two in a position to know -- hedged their words sufficiently so that we believe there was.
We do not know if there is a confidentiality agreement so the sordid details are locked up in case Potti ever begins a process of rehabilitating himself.
Is there any deal involving language in a notification to the NC Medical Board which handles licenses to practice medicine? Have federal or state prosecutor's expressed interest. What about the inspectors general of the two federal agencies that gave Potti grant money.
And if Duke has to give money back -- as to the American Cancer Society -- will it swallow the loss or seek indemnification from Potti.
Key point: While Duke's official announcements say Potti has taken "full responsibility," those seemingly sweeping words have limitations.
Text: “[Potti] accepted full responsibility for a series of anomalies in data handling, analysis and management that have come under scrutiny in the past months,” Willard wrote in a Friday e-mail to the genome staff.
"Full responsibility" for mistakes made with data, yes, but Potti has never acknowledged willful misconduct.
We should note here that Nevins request to the JNO for retraction revealed that one aspect of Potti's research involved 59 samples of ovarian cancer. Or what was supposed to be ovarian cancer.
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."
The Chronicle, which provided excellent, speedy, accurate coverage on Friday, first under the byline of Zachary Tracer, later joined by Taylor Doherty, got the only reaction from Potti himself that FC has seen throughout this mess. “It has been a difficult time, as you might imagine,” he wrote in an e-mail.
✔✔ THE POTTI LAB
There is no doubt that Potti was close to the people in his lab. His website for example has picture after picture of the Christmas party he has thrown for them each year. And word is, he has expressed concern now for "collateral damage" to trainees whose careers might be affected.
Precious little has been said about these people. They now work directly for Willard, who took over Potti's grants as Principal Investigator. "At the moment no one has lost his job," said Willard.
Key issue: did anyone know? Can anyone be held to the professional standard that they should have known.
✔✔ THE INVESTIGATIONS
There are two investigations underway. They will continue.
Unfortunately we do not know the scope of either, particularly since the Institute of Medicine is defining its own path. We have no idea who will be investigated.
In the case of the faculty misconduct review, we do not even know the people on the judgment panel.
This does not cut it. We were promised transparency.
We have new information about the key investigation by the Institute of Medicine, which we were initially very enthused about. This is an august body more concerned with public policy than science per se. It does not seem to have any specific qualification in scientific fraud. There are about 2,000 members of the Institute, with a surprising 81 from Duke, including the chancellor and medical school dean. We had the impression we were divorced from the organization doing the review.
This investigation must be lily white. No conflicts. No potential conflicts. No appearance of conflict. No appearance of potential conflict. The 81 from Duke should be required to stand down, suspend their membership, whatever device effectively severs them from all active work of the Institute at this critical time.
As this scandal metastasized, the list we wonder about in either inquiry has grown longer:
Dr Nevins, Potti co-author and his mentor, Barbara Levine Professor of Breast Cancer Genomics and director of Duke's Center for Applied Genomics and Technology. Target of the internal review last winter.
Dr Bernard Mathey-Prevot, Research Professor of Pharmacology & Cancer Biology, Professor in Pediatrics, Potti co-author, husband of Medical School Dean Nancy Andrews.
Dr Wm Barry, in Potti's lab and target of the internal review last winter. Co-author
Dr. David Harpole, Potti co-author, Professor of Surgery, vice chief of the surgical services division, associate professor of pathology.
Dr. Phillip Febbo, co-author, departed Duke for UCSF.
Associate Deans Cuffe and Kornbluth who signed off on last winter's review. Cuffe has just gotten new religion: “In retrospect, these trials should not have been done." Both should be barred from making statements on behalf of Duke University for the duration of this controversy for they have too much at stake personally, not to mention their conflict because they were promoted by and continue to report to Dean Andrews.
We just do not know what it means to be co-author of a medical journal article, how much work you do yourself, how much of the effort of other people you are charged with knowing. That's a question we will explore next.
Please read this is from the Cancer Letter: "When questions about Potti’s science emerged in scientific literature and in alarms sounded by internal critics, the Duke administration formed a protective barrier around the man they considered their star, forming committees that operated in secret, and then incorrectly portraying the findings of one of these committees as validation of Potti’s science." FC has no assurance whatsoever, that at the end of the two investigations, this ground will have been covered.
And speaking of conflict of interest issues, Duke divested itself of interest in licensing of Potti science, rather than face conflict charges that it was supporting Potti because it would make hoards from royalties if his theories provided a screening test for cancer patients. (The same issue is present in the Hellinga investigation, but ignored)
How much did Duke receive for its interests, from whom, and will they now get their money back since the science is bunk. The head of Duke licensing and VP Michael Schoenfeld both ignored FC e-mails.
Loyal Readers, since Potti first put forth his "discoveries" and was allowed to bring this bunk to clinical trials -- which is to say experiments on human beings -- the scientific community outside our Gothic Wonderland has raised questions. For four years, some entrenched people at Duke tried to discredit these challenges in any way they could, including disparaging remarks that bio-statisticians were not scientists are all, and that the MD degree yields more expertise in the emerging genome field than a Ph.D. At one point a Dean asked aloud who would believe a bunch of internet fools.
After a crescendo of concern, Duke was forced last winter to take an organized look at Potti -- an internal review with three outside consultants. While much of their secret report (Duke has refused to release it; anyone wanting a copy write Duke.Fact.Checker@gmail.com ) is highly technical, there are some unmistakable conclusions in plain English.
✔“the approaches (being used by Potti et al)... are viable and likely to succeed.”
✔ "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..... "
✔"...scientifically valid and with a few additions can be fully responsive to the comments of Drs. Baggerly and Coombes."
✔And most importantly reassurance for patients -- 107 or 109 already receiving Potti-determined treatment and more about to be enrolled: Use of the Potti science "does not endanger patients."
It takes a lot of guts, a lot of fortitude to stand up to a University so self confident and so arrogant, but luckily people with great inner strength were on the horizon. They should be recognized for the good they have done.
Uncle Dick, here's how you can recover and show some leadership at last:
Next Founder's Day, Duke should give its highest honor -- called the Medal of Honor I believe -- to Baggerly and Coombes. It should give its highest alumni honor to Paul Goldberg '81, editor of The Cancer Letter.
Further, Duke as an institution should nominate Baggerly, Coombes, Goldberg and The Cancer Letter for a special Lasker Award for public service, the highest US honor in medicine.
And Duke as an institution should nominate its son, Paul Goldberg '81 and The Cancer Letter, for journalism's highest recognition, the Pulitzer Prize.
✔✔ CONCLUSION AND PERSPECTIVE
Allow, FC please, to put Dr. Anil Potti into perspective.
Last week was a great one for Duke Medicine and its 25,000 employees. It started on Monday when Chancellor Dzau received the annual Research Achievement Award at the American Heart Association. The citation: “in recognition of his monumental contributions to knowledge of intricate disease processes affecting the heart and blood vessels, insightful discoveries that are positively impacting the health of millions.”
In case you forgot, a year earlier, another Dukie won: Dr. Robert Lefkowitz, Howard Hughes Medical Institute investigator, for "transformative discoveries of cellular receptors, seminal findings that have created a cascade of biomedical innovation leading to more effective treatments for human disease."
The week at Duke Medicine saw release of an important study on a new drug to prevent people with heart beat irregularities (called atrial fibrillation) from getting strokes. There was also release of the world's largest study of acute heart failure, clearing up questions about side effects from a key drug in use for five years but raising the question of "why trials of this magnitude, or even greater, are not required earlier in the course of drug development,” according to Dr. Robert Califf, vice chancellor for clinical research.
Also involving the heart -- some of the news tied to the Heart Association meeting in Chicago -- we learned about Duke discovery of a protein secreted from stem cells that could reduce scarring from a heart attack, leaving more of the muscle alive and pumping.
Duke was picked to monitor the standards of world-wide efforts to fight HIV and AIDS, with one goal being a vaccine. Right now there is too much inconsistency in the way scientists test and record their data. From Dean Andrews of the Medical School: "Patients, physicians and researchers all need to feel confident that a test on a blood sample performed in New York will yield the same results as the same test performed in London or South Africa as an example. Today, you might not find that.”
Meanwhile, a Duke research team believes it found out how the AIDS virus defeats antibodies that are dispatched by the human body to fight it.
From the medical school we run in Singapore came word that research into fruit flies had discovered the protein Zif, and the long range hope the protein can be manipulated in humans to fight the worst kind of brain cancer. Fruit flies.
And back in Durham, there was even a finding about how fungi protect themselves from genetic mutation during sex. Don't laugh please. It has a lot of implications for humans.
Beyond the Potti headlines, it wasn't such a bad week after all.
Thank you for reading Fact Checker. GO DUKE!