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Blog and Media Roundup - Monday, November 1, 2010; News Roundup
Topic Started: Nov 1 2010, 04:13 AM (294 Views)
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http://www.dukechronicle.com/article/co-author-potti-paper-retracts-work

Co-author in Potti paper retracts work
By Sonia Havele [3]
November 1, 2010


As investigations into Dr. Anil Potti’s research continue, Dr. Joseph Nevins, Potti’s mentor and collaborator, has now acknowledged errors in a paper whose results have been questioned for nearly a year.

The paper described a method of assigning patients to cancer treatments and was the basis of two cancer clinical trials being conducted at Duke. Two biostatisticians brought concerns about data in this paper to Duke officials last Fall, prompting Duke to conduct an investigation of the research. At that time, members of the investigation committee identified only minor problems that did not affect the validity of the research.

“I wonder if we should have caught it earlier, or if [Nevins and Potti] should have caught it earlier,” Dr. Victor Dzau, chancellor for health affairs and president and CEO of the Duke University Health System, told The Chronicle. “I think [it took] a deep dive, particularly by Dr. Nevins and new statisticians, to go through point by point and line by line to look at this issue.”

Nevins, Barbara Levine professor of breast cancer genomics and director of the Center for Applied Genomics and Technology, wrote in an e-mail that he is asking the Journal of Clinical Oncology to retract the paper because of faulty research. He sent the e-mail Oct. 22 to the 13 co-authors of the paper. The e-mail was obtained by The Cancer Letter and published Friday.

Nevins wrote that the research, published in 2007, “cannot show a capacity to distinguish responders and non-responders when the correct clinical information was used, contrary to what was reported in the paper.”

Potti and Nevins had previously claimed that they could predict patient response to certain chemotherapy drugs using genomic models.

Potti is currently under investigation for research misconduct and Dzau said that Nevins’ retraction will be considered by the investigation committee.

Nevins is not under investigation. He did not respond to several requests for comment.

Old problems resurface

The errors identified by Nevins call into question the scientific basis for two clinical trials involving patients at Duke.

Enrollment in those trials in addition to one other was temporarily suspended a year ago after Keith Baggerly and Kevin Coombes, biostatisticians at the M.D. Anderson Cancer Center pointed out problems with Potti and Nevins’ research. The trials resumed after Duke commissioned a review of the scientific work. Enrollment in the trials was stopped again this summer after allegations surfaced that Potti falsified portions of his resume, including his claim of being a Rhodes Scholar.

Baggerly and Coombes noted that the problems they identified last year are the same as those now recognized by Nevins.

“The errors that [Nevins lists] now in October 2010 in stating a rational for withdrawing the paper, are qualitatively identical to errors we identified and reported to Duke in November 2009, almost a year ago,” Baggerly said.

Coombes noted that the data was mislabeled in a way that scrambled those who responded to the drugs and those who did not.

However, Dzau said that such mistakes occur at institutions across the nation, noting recent cases at Harvard and Stanford universities.

“There are cases like this because science is by nature an exploration and an innovation,” Dzau said. “It’s important for us to see this as an opportunity to advance in science.... We become leaders because we learn from it, and we can become a better university for it.”

“I’m starting to worry”

In light of Nevins’ request for a retraction, questions have risen about whether cancer patients enrolled in the trials were harmed.

“I’m starting to worry,” Dr. Otis Brawley, chief medical officer of the American Cancer Society, said in an interview with The Chronicle. “[Potti and Nevins] might have caused some harm, I don’t know yet. I’m waiting for the end of the [Institute of Medicine] investigation.”

ACS partially funded Nevins’ and Potti’s research through a $729,000 grant awarded to Potti in 2007. Brawley said he is responsible for protecting both the ACS’s research money and patients involved in clinical trials. Brawley added that he is not convinced patients were harmed, but if investigations turn up fraud in Potti’s research, the IOM may ask that the grant money be returned.

Investigations continue

Paul Goldberg, editor of The Cancer Letter, reported the problems with Potti’s resume that led to serious investigations into Potti’s research.

“This is the ultimate tragedy of the whole thing. Had I not caught Potti claiming to be a Rhodes scholar, which has nothing to do with his research... this thing might have lingered on and kept on going, and patients could be harmed,” he said. “Even if they weren’t harmed, and I think they were, just the idea of wasting their time on the clinical trial of garbage is harm. It’s harm because it might give them false hope, it’s harm because it’s wasting the resources of Duke staff. It’s harmful in 100 different ways.”

After Goldberg identified issues regarding Potti’s resume in July, the University launched an investigation into his credentials and a research misconduct inquiry. The Institute of Medicine later agreed to lead an external review of both Potti’s research and broader issues related to certain predictive tests.

The University found “issues of substantial concern” in Potti’s resume but declined to give specific details. The research misconduct inquiry is still underway.

The IOM review committee is in its initial stages and will not issue a report until spring 2012. All the information related to the retraction will be provided to the IOM, Doug Stokke, assistant vice president of communications for Duke University Health system, told The Cancer Letter.

Dzau said that although the errors Nevins has identified are an important piece of the evidence being reviewed by the Duke committee, they do not necessarily show that research misconduct was committed. Other factors must also be considered, particularly whether the errors were intentional.

“The data is not valid,” Dzau said. “But... there is more to misconduct than just looking at the data.”

Taylor Doherty contributed reporting.
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http://dukefactchecker.blogspot.com/

Monday, November 1, 2010
Fake Potti Research Could Have Harmed Patients!!!!!!
✔Good day fellow Dukies.

The big news -- first reported by Fact Checker early Thursday evening but now with stunning new detail:

✔✔✔✔✔ The mentor of Dr. Anil Potti -- after four years of defending their joint research and claims to a break-thru in cancer treatment -- has stated their work has no validity. Or in the mentor's words, "no meaning."

The mentor is Dr. Joseph Nevins, a heavyweight in Duke medicine, Barbara Levine Professor of Breast Cancer Genomics and director of Duke's Center for Applied Genomics and Technology.

Nevins has sent an e-mail to the Journal of Clinical Oncology (JCO) requesting that it retract a 2007 research paper that he co-authored. The editors have yet to respond.

This paper claimed that locked in the DNA and RNA of each individual -- and in their cancer -- was information that revealed which form of chemotherapy would work best. Up until then, it was hit or miss; this was a major advance, major. Think Lasker, think Nobel Prize.

✔✔✔✔✔ Immediately, as news of Nevins' retraction request rippled thru the scientific community, a new storm engulfed Duke.

Experts say that Nevins has admitted that the clinical trials that followed the laboratory research -- more accurately described as experiments with human beings -- harmed patients. Up until this moment, Duke has steadfastly denied this; and in a Halloween statement, Duke affirmed "we do not believe that patients were endangered."

This sets up an interesting confrontation: who do you believe? The faculty member who was involved in the trials? Or the administrators responsible for oversight?

✔✔✔✔✔ Nevins revealed 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."

Translation: with the tumors being mis-identified, no one could tell what was what. In fact Potti concluded some patients were helped when they were not. He concluded some patients were not helped but they were. And out of this crap, he developed his theories about unlocking secrets contained in DNA and RNA and was allowed to experiment with human beings.

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."

✔✔ There's more: Duke's first official review of the Potti mess finally came last winter (after almost four years of questions, not one as the Chronicle states). This was a hush hush behind closed doors internal review; Fact Checker alone has reported it was led by Dr. John Harrelson, professor of orthopedic surgery and associate professor of pathology. A Deputy Fact Checker found he is a double Dukie, Trinity '61 and MD '64, who also stayed on at Duke to train on the House Staff. He is now retired.

Duke occludes this internal review, by mentioning its outside consultants -- and inferring it was an outside review. Wrong.

During this review, Potti was not suspended but he was not allowed to recruit more volunteers for his experiments. The people already in the trials were allowed to remain.

This weekend, Duke's medical PR man, Douglas Stokke, was sent out after Nevins denounced his own work to concede that the same 59 samples that Nevins looked at anew, had been analyzed last winter and found OK.

What???????

Dr. Sally Kornbluth, Duke Medical School vice dean for research, said last year's investigation did not "drill down" to re-check the actual raw data. She said the review team was "not aware that there were data integrity issues with the work."

Whoa. Whoa. Whoa.

We turn to the intrepid bio-statisticians at the M D Anderson Comprehensive Cancer Center, Keith Baggerly and Kevin Coombes, in a guest editorial in The Cancer Letter:

"In November, 2009, we identified and reported the exact problems now cited for retracting the paper.... Given that Duke knew of these problems, why were (Potti's) clinical trials reopened in January 2010?"

Kornbluth was one of two vice deans who signed off on the winter-time investigation. So she's got a lot at stake in its scoope and integrity. And that was just one of four investigations that we know of into the Potti mess.

Nevins' retraction request is not part of any of those investigations. So where did it come from? How did it occur? From Duke PR: "We cannot speak for Dr. Nevins and his team who analyzed the data and came to the conclusion regarding the need to request a retraction."

Keep reading, there's more.

✔ Speed check number one involves other Duke scientists who co-authored the JCO (Journal of Clinical Oncology) article that Nevins wants withdrawn. Where do they stand? Why are they silent?

These include two big shots: Dr. David Harpole, professor of cardiovascular and thoracic surgery, and vice chief of the entire Division of Surgical Services. And Dr. Phillip Febbo, a specialist in prostate cancer who has since left Duke for the University of California - San Francisco. There are also other junior Duke physicians and scientists, several of whom have left for other places including UNC.

✔ Speed check number two involves the request to retract the JCO paper. It's rather unusual -- to say the least -- for a co-author to initiate a retraction request -- and even more unusual for one co-author to proceed unilaterally without consent of all the other authors.

The Cancer Letter -- whose original reporting on the Potti mess has prompted, forced and embarrassed Duke into action and is fully worthy of major awards for investigative journalism -- says that Nevins sent an email October 22 to his 13 co-authors to advise them. That's a whole lot different from their consent.

Key issue: Did Potti respond? Did he agree to sign this correspondence? Did all of the co-authors sign? Are all of the co-authors in agreement that the paper should be retracted?

Key issue: Over the Halloween weekend -- yes some of this stuff is so scary that I threw that in again -- Chancellor Victor Dzau sent all medical personnel an E-mail. He referred to "A scientific misconduct investigation regarding Dr. Potti that began several weeks ago." In fact, while the Institute of Medicine has agreed to do this external, unfettered, complete investigation, it will not begin until next year.

Yes this is the same Dr.Dzau who told us in an earlier e-mail that the very investigation would be into "the science conducted by Drs. Potti and Nevins."

Or as they'd say in Brooklyn, hey Victor, what happened to Joe?
FC does not believe the above Chronicle article is correct when it states Nevins is not under investigation.

Or for that matter, what happened to William T. Barry, who received his Ph.D. at Carolina in 2007 and is an assistant professor of bio-statistics and bio-informatics, working in the cancer center? Loyal Readers will remember FC's taking the wraps off Duke's secret report dated last December. That's when welearned tdhat Barry -- along with Potti and Nevins -- was investigated.

✔ ✔✔✔ Speed check number three involves the tests that were run to confirm Potti's data -- the precise time-line being in question.

What a tug of war it must have been between Nevins and his superior, Huntington Willard, Ph.D., Vice Chancellor for Genome Sciences and professor in the Institute for Genome Sciences & Policy!!!!!

(Nevins has refused all media requests for an interview; Willard responded immediately to a Fact Checker inquiry over the weekend on another aspect of the Potti matter. We are still at work trying to sort out other things to ask Willard who has indicated he would respond.)

A consistently reliable mole tells FC that Willard called a meeting with everyone in Potti's lab -- believed to be about 20 people, a total derived from pictures of those attending the annual Christmas party that Potti has thrown. Willard said he was taking over as Principal Investigator for Anil’s grants.

(This is more than a technicality. The rules for most grants provide that the Principal Investigator -- PI -- cannot be absent for more than three months. One key grant for this research expires November 1 and it will be interesting to see how Duke handles continuing the lab. If some disgruntled employees are let go, FC wants to hear from them!!!!).

And Willard put Bala Balakumaran, Ph.D., Research Associate, Senior Staff, Center for Applied Genomics & Technology in charge of repeating the Potti experiments -- with specific instructions to report to him, Willard.

Nevins apparently contradicted that, telling Balakumaran that only portions of the Potti experiments should be repeated -- and forget Willard, the results should be given to him.

The mole tells FC there were several rounds in the tug of war with Balakumaran being "cajoled" by Nevins and receiving "conflicting orders" from two superiors.

Loyal Readers, this is not a novel. All this is going on in Fitzpatrick!!

✔✔The FC mailbox overflowed this weekend. Here are some excerpts:

"Is Nevins falling on his sword or throwing Potti under the bus?"

"The rest of the investigation will determine who was responsible and if deliberate fabrication or falsification were involved. Admission of reckless incompetence may be the only way out for Potti and Nevins."

✔✔ Potti remains on administrative leave. Paid. "No change" in status, said Michael Schoenfeld, Duke PR in response to the latest outrages. Loyal Readers, I do not know what a Duke faculty member, Duke researcher, or Duke doctor has to do to get canned.

Nor do I know who is protecting this clown.

✔✔✔About 25,000 people in the medical enterprise at Duke, and their continuing discoveries and care have earned this university renown. As the Chronicle notes, they are led by Chancellor Dzau, and FC expresses complete confidence in his integrity.

He alone among Duke's administrators has kept his pledge to keep the Potti mess "transparent."

FC and he have had substantial discussions of not only this, but other issues, with FC given more time than ever anticipated, allowed to explore every angle.

Unfortunately our essay this morning -- as happens so often in journalism -- is not about the good being done by so many but about a few who are sinking their ship. The only issue on the horizon is how many will go under with the vessel.

✔ Thank you for reading Fact Checker on good days and bad.
Posted by To reach Fact Checker at 1:22 AM
Saturday, October 30, 2010
Chancellor Dzau sends E-mail on Potti Mess
Fact Checker will have a special report on the Potti mess Monday morning. Please check back.

The text of the Chancellor's e-mail to Duke Medicine employees follows:

I wanted to send a brief note to let you know that you may see some media reports -- most notably in tomorrow's News & Observer -- related to a request by Dr. Joe Nevins to retract an important scientific paper authored together with Anil Potti, MD in the Journal of Clinical Oncology. The request for retraction of this paper is the latest in a series of regrettable events that have occurred over the past year related to the science that was the source of the requested retraction.

It's important for you to know that the well-being of our patients, especially patients who volunteer to participate in clinical trials, is our highest priority. In this situation, we are confident that we acted deliberately and appropriately as an institution to both fully protect research participants and fairly evaluate the science and actions of the involved faculty scientists.

While a regrettable situation, I also recognize and appreciate the tenacity and scrutiny of the scientists who raised the questions about this data and the study that is being retracted. A scientific misconduct investigation regarding Dr. Potti began several weeks ago, he continues to be on administrative leave, and I'm pleased that the Institute of Medicine has initiated a major national review of this situation and this field of research.
Posted by To reach Fact Checker at 11:31 AM
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http://www.newsobserver.com/2010/11/01/773196/doctors-a-blight-on-duke.html

Published Mon, Nov 01, 2010 02:00 AM
Modified Mon, Nov 01, 2010 01:03 AM
Doctor's a blight on Duke

Months before a Duke student's "research" on the sexual prowess of several Blue Devil athletes became an Internet phenomenon, an esteemed cancer researcher came under attack for padding his résumé and for scientific findings that couldn't be replicated.

Don't kick yourself if you've overlooked the case of Dr. Anil Potti.

After all, how is cancer research supposed to compete with a sordid story of sex among college students?

You will hear more about Potti, though, because the fallout from Potti-gate could be far more costly to Duke's reputation as a pre-eminent research institution and to the search for effective cancer treatments.

Potti is on paid leave while the university investigates his work. One of his key collaborators, Joseph Nevin, asked The Journal of Clinical Oncology on Friday to retract the printed research he and Potti submitted. Reassessing their work, Nevin found it failed to support the conclusions they reported.

The journal is reviewing the retraction request.

Friday's bombshell followed an announcement from Duke spokesman Michael Schoenfeld, who told reporters in late August that "issues of substantial concern" had been identified in a review of Potti's academic credentials.

Among the embellishments were claims that Potti received a prestigious Rhodes Scholarship.

You can't blame Duke for the actions of a single researcher - physicians and researchers I spoke with said integrity and trust are critical parts of medical research.

But you can blame Duke for its failed pre-employment background check on Potti.

Now that Potti's collaborator has acknowledged their work doesn't hold up, the main question is: How will the controversy affect much-needed cancer research?

Dr. Alan Kritz, an oncologist with the Cancer Centers of North Carolina, said it won't help.

After all, researchers depend on willing patients to participate in clinical trials.

"Any time you have an investigation where data is questioned," he said, "it certainly puts doubt in people's minds and makes them hesitant [to participate]. They wonder if the research is safe."

Kritz, who was voted one of America's best doctors, said one "bad apple" can taint the reputation of other researchers.

But he's confident that if Potti is found to have peddled more bad science, then his case is an aberration.

"For every one investigator who does something wrong, there are hundreds who play by the rule," he said.

But an extra phone call to check Potti's background could have saved Duke from a possible cancer on its reputation.
barry.saunders@newsobserver.com or 919-836-2811
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