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More on the Potti scandal
Topic Started: Aug 11 2010, 08:56 AM (8,322 Views)
Quasimodo

Character is destiny.

Imagine how different these events might have played out--and how much a leader Brodhead might have been--
had he taken the moral high road regardless of the cost...

Now how will he be remembered?
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kbp

Quasimodo
Aug 18 2010, 07:20 PM
Character is destiny.

Imagine how different these events might have played out--and how much a leader Brodhead might have been--
had he taken the moral high road regardless of the cost...



Now how will he be remembered?
I think Payback is our best candidate to answer that question!!
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chatham
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http://dukefactchecker.blogspot.com/


Thursday, August 19, 2010
The Potti Mess: Why the delay?
✔Fellow Dukies, FC here. Friday, August 20.
Three weeks ago today, the Chronicle posted a special summer-time story about two investigations into the life and work of cancer researcher Dr. Anil Potti.

We will dispose of the "science" probe first, even though the immediate reason for this post is the internal "credentials" investigation.

For the scientific investigation, Duke will line up outsiders of impeccable reputation (external is the word used) to re-do an in-house investigation that Duke had completed last winter clearing Potti. FC need not recount for Loyal Readers the storm that this decision caused.

We learned three weeks ago today that Chancellor Dzau was talking -- even before he wrote an e-mail to the medical school faculty -- with Dr. Harold Varmus, Nobel Prize winning director of the National Cancer Institute. Varmus in turn had us in touch with the National Academy of Sciences which seemed ready to undertake -- and finance -- the investigation. Not bad.

Since Dzau's e-mail, we have not heard a damn peep. This is unacceptable and inspires no confidence. With the university's crown jewel, its medicine, under siege, and its reputation being sullied world-wide, we all have a vested interest.

No one is asking for information about Potti. We are asking for information about what Duke is doing. I am sick and tired of the PR effort to obfuscate the two.

We understand the scientific investigation is going to take time, months, maybe a year. That does not excuse the failure to inform us of the reason for the delay.

✔Now, the internal probe. If you think Fact Checker is worked up about the external probe, watch me launch into the internal probe for faculty misconduct, that is, Potti's lying about his credentials.

Three weeks ago today, Dzau gave the Chronicle an interview. He said this probe was "close to being completed."

The review had been in the hands of Dr. Michael Cuffe, vice dean of the medical school, but for reasons unannounced, Provost Lange superceded him. On that day Lange told the Chronicle the investigation would be completed "promptly." Indeed, Cuffe had offered a timetable when he was in charge that meant a verdict no latter than July 30.

So what the hell is going on? In three weeks since Dzau's e-mail, we have only two official statements. One says Duke wanted to give Potti a chance to find a lawyer; surely that has been done.

The other was a request from President Brodhead who joined with editors of the Herald-Sun for a chat, a request that stakeholders not reach a conclusion because "every allegation is not a truth."

Brodhead went on to embarrass himself and this university: "We want, therefore, is for people to back off until they can learn whether the allegation was true or whether the allegation was false or if there is some intermediate explanation..."

With so much at risk, stakeholders in Duke deserve a leader who is going to make solid pronouncements defining honor. Not muddle this mess more by diluting the concept.

✔FC has made NO inquiry to Duke administrators about matters of substance involving Potti. FC has requested substantial information about the process involved in this review -- due process if you want a legal phrase.

This has nothing to do with the turmoil of the moment, and everything to do with fairness. One of the factors distinguishing the American system of government is our open knowledge of the judicial system, not being subjected to a kangaroo court or star chamber where we do not even know the rules.

OK Lange has the investigation. Will he make a decision, or will he make a recommendation to Brodhead?

Is Lange operating alone, or did he create a panel? Who is on the panel? If we cannot be told, why?

How will the panel operate? Is there a "prosecutor" who will go up against Potti's lawyer?

Will the panel make decisions by a unanimous vote, by a super majority, or by a simple majority?

What misconduct is needed for Duke to fire a faculty member? Is one gross instance -- like a bald flat out lie about a Rhodes Scholarship -- enough? Or must there be a pattern of misconduct, which, as Loyal Readers know, FC has outlined in great detail.

A Deputy Fact Checker did ask two questions relevant to Potti: Does he have tenure? And is his suspension from his post as a medical school associate professor, or a cancer center researcher, or both?

The Deputy also asked what it means when a faculty member is placed on "administrative leave" with full pay, in as much as we have unconfirmed reports of Potti in his office and lab. Again, a policy question very much in the public interest, not a Potti question.

As FC has noted, Michael Schoenfeld, VP for public relations and obfuscation, has not even acknowledged any of these requests. You can bet your seats in Cameron to the Carolina game that the flack would have answered immediately if we were cheering Brodhead's leadership.

✔Mr. Brodhead, your penchant for secrecy..... wrong word.... Mr. Brodhead, your insistence on secrecy in everything surrounding the Allen Fortress is costing you whatever support you have left on this campus. To borrow some words from history, and not to be cute about it by repeating the name of the disease, a cancer grows on your presidency.

✔None of this touches the factor that bothers me most: 107 or 109 patients whose treatment for lung and breast cancer was determined by the "science" of Potti and his crew. These people gave up other therapies to participate in his human experiments, and a Who's Who of genome researchers world-wide says they are in substantial danger.

I gather Chancellor Dzau does not share that evaluation. But we need more re-assurance than what FC can "gather" on such a crucial issue. Has each of these people been contacted? Tell us what Duke told them? Is there a letter? Let's see it.

Or are the lawyers muzzling you -- knowing that this is going to cause a cauldron of malpractice lawsuits not only from the 107, but from more than 1500 who underwent painful and risky procedures to donate tissue for Potti to check their DNA and RNA.

It has never meant more to be a stakeholder in Duke, for this institution is at a moment of great challenge that requires our vigilance to protect our great school's integrity. Stakeholders, from the newest freshman to the oldest alum, from someone laboring earnestly and loyally at the bottom of the pay scale to the retired professor who held an endowed chair, have a great responsibility. This is not a matter for the current batch of administrators alone, as they themselves have shown.

✔FC will post the promised essay next time: Comparing the Potti Mess and the investigation into Hellenga's Hell. The two-faced standard the Brodhead Administration is using for conflict of interests.

Thank you for reading and supporting FC.
GO DUKE!!

Email: Duke.Fact.Checker@gmail.com
Blog: http://dukefactchecker.blogspot.com/
Posted by To reach Fact Checker at 9:25 PM 1 comments
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Payback
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I don't see anything about the Potti scandal on Richard Brodhead's Wikipedia site yet.
Van de Velde's reinstated lawsuit is there, and the Lacrosse frame.
It falsely identifies him as a "scholar" when it should have said "critic."
Edited by Payback, Aug 22 2010, 01:27 PM.
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chatham
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Fact Checker comments about Potti et al. should also be listed here.


Potti Mess: two researchers who blew the lid off add new perspective
The researchers whose intrepid pursuit of truth led them to stand up to Duke officials and question repeatedly the cancer "discoveries" of Dr. Emil Potti are giving their first interviews to the news media, and Fact Checker does not like at all what he is hearing.

The researchers are from the renowned MD Anderson Cancer Center at the University of Texas, Houston. They are Keith Baggerly, Ph.D., associate professor of bioinformatics and computational biology and his colleague, and Kevin R. Coombes, Ph.D., professor and deputy chair of the department.

-- The researchers suggest deep fraud in Potti’s breath-taking claim to discovery of unique information locked in DNA and RNA that would allow doctors to tailor their treatment for lung and breast cancer to the individual, selecting the proper chemotherapy drug and the precise dose.

The next paragraph is the FC understanding of this highly technical situation. The paragraph following is from Oncology Times.

Baggerly explained that Potti's research showed a gene -- ERCC1 -- responded to treatments in a pattern determined by DNA and RNA. However, the tool that Duke investigators said they used in their experiments -- their commercial micro array chip -- does not recognize the ERCC1 gene at all.

From Oncology Times: "Dr. Baggerly says that (Potti and crew claimed) their data showed that expression of a particular gene, ERCC1, correlated with response to some agents. However, the commercial microarray chip the Duke investigators said they used in their experiments does not have that gene."
.
Loyal Readers, how could Potti, Nevins and Barry possibly reach their conclusions? “I admit this is one for which I do not have a simple, charitable explanation,” said Baggerly sadly.

-- Time after time, Baggerly and Coombes say they were ignored by the administration at Duke. “We have been yelling about the science for three years…. So I find it ironic that (revelations about Potti’s fake Rhodes Scholarship) got things rolling,” said Baggerly. “But I am sufficiently opportunistic that if you give me a way to get attention paid to the science--or to get trials that I really disagree with suspended and have people look at them--I will take that opportunity.”

✔In a separate interview, Dr. Otis Brawley, chief medical officer, American Cancer Society, which paid for some of the Duke "research" and may demand its money back, said Duke may have thirsted for the big bucks it stood to make on licensing Potti’s discoveries -- rather than checking them out.

Brawley said that the community of researchers trying to beat cancer used to be able to depend on a university to oversee its faculty. “But now, in the current age, when people are patenting research and every university has an office of intellectual property, the university, which is supposed to police and supervise the investigator and make sure they are doing things properly and with integrity, has a conflict of interest.”

More Brawley: With the big rush to claim intellectual property rights, “There can be a tendency to rush, and to get sloppy as one rushes to get a product or finding.... I really think our attempt to do this quickly and our attempt to do this with some secrecy, with proprietary nature to it--that is what is hurting us.”

Fact Checker conclusion: Duke's administration is reviewing the lies in Potti's resume, the Rhodes Scholarship and so forth. It claims to be making arrangements for a top-flight scientific body to come in and review all of the science of Potti and his co-scientists, an "unfettered" examination that can move in all directions. But these two steps are not enough.

✔✔It is clear that we have either malfeasance or nonfeasance at the highest levels of Duke. At their October 2-3 meeting, the Trustees must intervene, performing their highest function which is to protect the integrity of this institution. We need an outside probe of the administration, and yes, some hard decisions from the Trustees.

Fact Checker is working on the conflict of interest angle, but this is taking longer than anticipated. Check in a few more days.

Fact Checker would like anyone in a Potti trial -- or anyone who knows of someone -- to make immediate contact.

✔Thank you for reading and caring about Duke.
Duke.Fact.Checker@gmail.com
Archive: http://dukefactchecker.blogspot.com/

Posted by To reach Fact Checker at 4:25 AM 0 comments
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Quasimodo

Quote:
 
✔✔It is clear that we have either malfeasance or nonfeasance at the highest levels of Duke. At their October 2-3 meeting, the Trustees must intervene, performing their highest function which is to protect the integrity of this institution. We need an outside probe of the administration, and yes, some hard decisions from the Trustees.


And not for the first time.


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sceptical

http://www.dukechronicle.com/article/duke-nears-final-stages-naming-external-review-body-potti-case

Duke nears ‘final stages’ of naming external review body in Potti case

By Tullia Rushton
August 22, 2010 Print Article

The external organization set to lead the investigation of Duke cancer researcher Anil Potti’s allegedly flawed findings is nearly determined.

Dr. Victor Dzau, chancellor for health affairs and president and chief executive officer for the Duke University Health System, said the University is almost certain about which organization will conduct the external review of Potti’s research.

According to The Cancer Letter, National Cancer Institute Director Harold Varmus has contacted the Institute of Medicine to request that the organization lead the review of Potti’s findings.

The external organization set to lead the investigation of Duke cancer researcher Anil Potti’s allegedly flawed findings is nearly determined.

Dr. Victor Dzau, chancellor for health affairs and president and chief executive officer for the Duke University Health System, said the University is almost certain about which organization will conduct the external review of Potti’s research.

According to The Cancer Letter, National Cancer Institute Director Harold Varmus has contacted the Institute of Medicine to request that the organization lead the review of Potti’s findings. Dzau declined to comment on whether IOM was in fact the organization that Duke has been in talks with, citing an confidentiality agreement with the organization’s president.

“It could negatively impact the decision making [with respect to Potti’s work] if we don’t keep the identity [of the organization] confidential,” Dzau said. “We are in active discussion, if not the final stages, of arranging for a totally neutral, objective [and] distinguished panel of reviews conducted by a most distinguished organization.”

The University completed its own review of the controversial cancer research—used to tailor chemotherapy with individual patients—in January after charges by biostatisticians Keith Baggerly and Kevin Coombes of MD Anderson Cancer Center alleged that Potti’s work contained errors. At the time, Duke stood behind the research, noting that it was “viable and likely to succeed.”

But recent allegations that Potti falsified his resume and qualifications on resumes for federal funding brought Potti’s research to the forefront. Potti is accused of posing as a Rhodes Scholar, falsely claiming to be a recipient of numerous awards and claiming work under a mentor who told The Cancer Letter he did not know Potti at the time.

For the second investigation, Dzau noted that the Duke community, as a whole, believes it is the best decision to use an outside group to conduct a review of Potti’s scientific work and ethics.

“I’m working to get an external organization... [with] high credibility to take over and do all of it without any Duke involvement,” Dzau said. “In other words, we’ll provide everything they need to make it transparent, and we will not be engaged in that review in order for the scientific body to be able to do it in an open and transparent and objective fashion.”

The University is currently conducting an internal investigation geared to assess the validity of Potti’s credentials but has not yet released the results of whether Potti is guilty of internal, academic misconduct.

The investigation is being led by Provost Peter Lange and a panel of faculty, the members of which have not been released. The review of Potti’s qualifications has now been ongoing for a number of weeks, although in late July Lange said he expected the investigation to end “promptly.” Lange could not be reached for comment on the progress of the internal review.

Taylor Doherty contributed reporting.
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sceptical

7:02 AM
August 23, 2010

Fact Checker
✔Fact Checker here. Chronicle, it's the first issue of the year and already you are giving me a headache.

This article does not even begin to suggest the dimensions of this scandal:

A) It is not only Potti who is on trial for bum science. At least two others -- Nevins and Barry -- are standing right next to him. And trust me, the list will grow and grow. Potti grabs the headlines because he also faked a Rhodes Scholarship.

B) It's not simply that Duke's own investigation last winter cleared Potti and the others. For more than three years, the administration abetted Potti and the others, silent in the face of a rising chorus from the genome community world-wide. The heat grew, Duke had to cave. Trust me a second time, the administration itself will face inquiry.

C) How can the Chronicle write its introductory story on Potti without noting that more than 100 patients are currently receiving treatment for their lung and breast cancers based upon his bum science? To participate in these human experiments, people relied on the imprimatur of Duke and they did not pursue other therapies that might have worked better. Trust me again, Duke's role will explode.

D) This past weekend, Harvard's disciplining of a professor who faked his science came out of the closet because of an expose in the Boston Globe newspaper. Two aspects interested me:

-- that federal prosecutors are investigating fraud in securing grants. Chronicle, have you checked with the U S Attorney or with state medical license authorities?

-- that Harvard stated it will review its faculty disciplinary policies, presumably including the secrecy surrounding them and apparently including the entire concept of tenure. Convicted of eight counts of academic fraud, the tenured professor says he looks forward to returning to his research and classroom. As they say in Brooklyn, the bum should have been fired.

Grrrrrrrrrrrrrrr. Today's Chronicle story ran 470 words. This scandal cannot be covered that simply, and Fact Checker respectfully suggests the newspaper find more room.
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Payback
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sceptical
Aug 23 2010, 09:03 AM
http://www.dukechronicle.com/article/duke-nears-final-stages-naming-external-review-body-potti-case

Duke nears ‘final stages’ of naming external review body in Potti case

By Tullia Rushton
August 22, 2010 Print Article
. . .
According to The Cancer Letter, National Cancer Institute Director Harold Varmus has contacted the Institute of Medicine to request that the organization lead the review of Potti’s findings. Dzau declined to comment on whether IOM was in fact the organization that Duke has been in talks with, citing an confidentiality agreement with the organization’s president.

“It could negatively impact the decision making [with respect to Potti’s work] if we don’t keep the identity [of the organization] confidential,” Dzau said. “We are in active discussion, if not the final stages, of arranging for a totally neutral, objective [and] distinguished panel of reviews conducted by a most distinguished organization.”
A committee job headed by Houston Baker and John Burness.
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Baldo
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✔None of this touches the factor that bothers me most: 107 or 109 patients whose treatment for lung and breast cancer was determined by the "science" of Potti and his crew. These people gave up other therapies to participate in his human experiments, and a Who's Who of genome researchers world-wide says they are in substantial danger

What is the potential monetary liability for Duke? I am sure they had to sign waivers to be in the program, however falsified science is another story. Fraud changes things.

As for moral & ethical responsibility that went out the door long ago. The Duke Lacrosse Frame exposed a campus community where far too many were forced to remain silent while bullies pushed an agenda.

"Honesty is the first chapter in the book of wisdom.” Thomas Jefferson
Edited by Baldo, Aug 23 2010, 11:15 AM.
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Q.A.
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Q.A.
“The two-faced standard the Brodhead Administration is using for conflict of interests.” and,

“Fact Checker is working on the conflict of interest angle,”

--------------------------------------------------------------------------------------------

IMO “Appearance of Conflict of Interest” is a standard obfuscation in academia.

There is or is not an actual conflict of interest.

Actual conflicts of interest are so common as to be within normal limits; there is no need to deny them; their existence is not the problem.

The problem is improper action.

Some actions are made improper only by the presence of a conflict of interest.

The problem is: actions-made-improper-by-the-presence-of-a-conflict-of-interest.

Nepotism, which is a component of the Potti cover-up, is the name of such an improper action.

However, although Fraud is another improper action in the Potti scandal, blending Fraud into “Appearance of Conflict of Interest” only promotes the obfuscation.

Fraud is fraud; lying is lying.

Duke’s self-policing is the prime conflict-of-interest here.

The Duke “Leadership” is in way over its head.

The “appearance” Duke has been acting to eliminate here is of the actual unethical behavior, rather than eliminating the unethical behavior itself,

“Duke” has obfuscated, improperly-denied, or tried to keep obvious-ethical-breaches hidden, instead of frankly exposing and correcting them.

Duke-breaches are already in the academic-public domain; we already know-about them.

Duke’s incompetent administration procrastinates ending the problems the public already knows-about, keeping hidden the problems the public does not yet know-about.
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chatham
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http://journals.lww.com/oncology-times/blog/newestnews/pages/post.aspx?PostID=34

Saturday, August 21, 2010
Duke Scandal Shines Light on Systemic Problems in High-Throughput Experiments
Ahead of Print:
Duke Scandal Shines Light on Systemic Problems in High-Throughput Experiments
By Rabiya S. Tuma, PhD


Posted Image

The recent revelation that Duke University researcher Anil Potti, MD, falsely claimed he was a Rhodes scholar on his curriculum vitae shocked the oncology community. Yet more important for the field is evidence that his microarray data, which led to three clinical trials, contains numerous inaccuracies. Remarkably, scientific critics have been trying to alert oncologists to those experimental problems for three years with little success.
“To a certain extent, I find it ironic that we have been yelling about the science for three years, but that is not what got things rolling,” said Keith Baggerly, PhD, Associate Professor of Bioinformatics and Computational Biology at the University of Texas MD Anderson Cancer Center, who uncovered the errors with his MD Anderson colleague Kevin R. Coombes, PhD, Professor and Deputy Chair of Bioinformatics and Computational Biology. “But I am sufficiently opportunistic that if you give me a way to get attention paid to the science--or to get trials that I really disagree with suspended and have people look at them--I will take that opportunity.”
And take that opportunity he has. With the credentials scandal grabbing the field’s attention, Dr. Baggerly, Rafael A. Irizarry, PhD, Professor of Biostatistics at Johns Hopkins Bloomberg School of Public Health, and nearly 40 other biostatisticians and bioinformatics specialists are using the spotlight to call for better standards and more reproducibility in high-throughput experiments, including microarray and proteomic work.
In a letter submitted to Nature, the group notes that independent replication of results is key to science, yet few published microarray studies contain enough detail to allow for it. To correct the problem, they ask journals to require that study authors provide more detailed methods and set out five areas that need specific attention.
Experts note that this is not the first time the field has been misled and say that while the potential new standards are debated in journals and blogs and Internet discussion groups, there are some simple questions and issues oncologists can consider to ensure the community is not misled again by sexy but erroneous data.

Making the Case for More Reproducibility
To illustrate the need for reproducibility, scientists can point to two cautionary examples in oncology, the one from Duke and a proteomics strategy for early detection of ovarian cancer. In each case, the high-throughput data looked impressive on the surface but was subsequently found to be full of mistakes. However, because the papers reporting the work did not contain enough methodological details to enable independent testing and replication, the problems came to light only after the oncology community had invested substantial resources in follow-up work or clinical trials.
“In both cases, the results, as initially reported, were clinically really important,” said Dr. Baggerly. In the case from Duke, Dr. Potti and colleagues claimed they were able to use gene expression signatures derived from cell lines to predict the best chemotherapy for an individual patient. With the proteomics data, Lance Liotta, MD, PhD, then at NCI, and Emanuel Petricoin, PhD, then at the FDA, and colleagues thought they had found a way to diagnose early-stage ovarian cancer based on a blood test.
“Since these would be wonderful [tools] if they worked, they also shared another characteristics,” Dr. Baggerly said. “Within just a few weeks of these papers appearing, we over in bioinformatics got several requests from MD Anderson clinician researchers saying they would like to do it here. But once we started digging into the data, we (a) could not reproduce the results reported and (b) identified other patterns within the data that indicated that something weird was going on.”
In the proteomics project, it appeared that the researchers ran the samples in batches, rather than randomly intermingling samples from controls, cases, and women with benign disease. And some experimental condition seemed to change between the time the team started running the samples and finished. Therefore, controls looked different from cases and both looked different from benign disease, but the difference was due to the experimental design, not the underlying biology.
“If you’ve got machines that are sensitive enough to pick up subtle differences in mRNA or protein levels associated with a small change or early disease, I can guarantee that machine is going to be sensitive enough to detect that you changed reagent lots. It is going to pick up batch effects, and you have to keep that in mind,” Dr. Baggerly said.
In Dr. Potti’s experiments, the MD Anderson team uncovered multiple problems, some of which are easy to understand and others for which Dr. Baggerly says he has no easy explanation. In the first category, for example, the researchers appear to have shifted the data and the labels relative to one another, so that they were off by one.
In the second category, Dr. Baggerly says that the Duke investigators said their data showed that expression of a particular gene, ERCC1, correlated with response to some agents. However, the commercial microarray chip the Duke investigators said they used in their experiments does not include that gene. “I admit this is one for which I do not have a simple, charitable explanation,” Dr. Baggerly told OT.

New Standards for Reproducibility
Finding the problems in both projects took substantial amounts of time because the methods included in the papers were inadequate. Therefore, Drs. Baggerly and Coombes had to try to figure out and recreate what was done, rather than just retest the model. For the Duke experiments, Dr. Baggerly estimates they spent 1,500 hours trying to figure out what was done and what went wrong. And while he and Dr. Coombes were able to spend that time in these two instances because of the potential clinical importance, Dr. Baggerly says other mistakes and flawed results remain undetected in the literature--in part because the methods sections are insufficient to allow for reproducibility.
Numerous other specialists see the problem as well. For example, in a study published in 2009, investigators assessed 18 published microarray experiments and found enough detail to understand exactly what the authors did in just two of them.
“If you look at the really big picture--and this is the key point--the entire purpose of methods sections in science articles is to let someone else reproduce what you did,” said David F Ransohoff, MD, Professor of Medicine and Cancer Epidemiology, Cancer Prevention, and Control at the University of North Carolina at Chapel Hill. “That is really why it is there. So I can see what you’ve done, build on that, or, if I want, see if it is right or wrong. And what has happened as studies have gotten more complex, is that is harder to do. But we, as a scientific field, may have to decide if the solution to that is to say that we are not going to try anymore, or to try to figure out how we can preserve that goal, which is a very important goal in science.”

Letter Submitted to Nature
With that concern in mind, the group of biostatisticians and bioinformatics experts, writing under the name “Scientists for Reproducible Research Working Group,” have submitted a letter to Nature requesting that journals require study authors to provide access to the entire data set used for the experiments with adequate annotation. They also want inclusion of information on data provenance, including URLs and database accession numbers, publication of the software code used to analyze the data, step-by-step descriptions of all data manipulations that were done by hand and thus not included in the software code--this might include the steps performed in point-and-click spreadsheet programs, for example--and any prespecified research plans.
Dr. Irizarry and others acknowledge that this may add some work for study authors but is in the best interest of science, and is really about documenting their own work. “Data provenance should be very clear,” he said. “It should be clear what you started with and, if it changes, how that transformation happened. That is not that easy. It is work, but you can’t get around it.”
And having those exact methods available can also help researchers recheck their own data and correct any errors or omissions--before they put it in print. “You can get fooled by artifacts, if you get results that aren’t right, but appear to be right, and you don’t know how to check for problems,” he said.

Successful Predictors
There have been successful predictors discovered or developed through this type of technology, including MammaPrint and Oncotype DX. “I get a little ticked when people blame the technology, saying it is dirty and what not. But if you know how to use it and not get fooled by artifact and bias, you can do well with it,” he said.
“One metaphor I use is the difference between a shovel and a digger. I can make a hole with a shovel, it would take me a long time, but I can do it. A person who knows how to use a digger would do it much faster than me and make a fine hole. If I get on the digger, I will make a mess. I don’t know how to use it. Is it the digger’s problem? No. It’s that I don’t know how to use it.”\
In addition to laying out what should be included in the methods section, the Scientists for Reproducible Research Working Group suggest in their letter to the editor, as well as in online discussions and interviews, that study authors who do not want to include the software code or some other aspect of the specified methods should have to explain the omission.
“If in submitting a paper to the journals, you choose not to supply the raw data or code, I want you to have to explain that decision,” said Dr. Baggerly. “Sort of like a disclosure of [financial] conflict of interest. If you say I am not supplying code because it might interfere with future intellectual property rights, then that is something I can use in evaluating how strongly I take the results in this paper.”
Otis Brawley, MD, Chief Medical Officer for the American Cancer Society, which funded some of Dr. Potti’s follow-up work and clinical trials, agrees with the main goals of the Working Group. “I think [software] code and data do need to be available at a level they have not been, although I think they can keep something proprietary, but there has got to be a limit on that,” he said.

Back to Basics
No one expects that the changes requested by the Working Group will be adopted quickly. Therefore, readers and data consumers have to assume some of the burden for making sure the data are valid before the community charges ahead with expensive research efforts or clinical trials based on the novel findings. And for that, the experts interviewed for this article emphasized a need to go back to basics, not only in the Methods sections of papers but also in the consumption of data.
For example, if the data look too good to be true, then people should be cautious. “Science usually proceeds in a rather gradual fashion,” said Donald Berry, PhD, Professor and Head of the Division of Quantitative Sciences at MD Anderson. “If all of a sudden we go from no predictive ability to extremely good predictability, it ought to lead you to think that something is not right there. Contamination can be perfect, biology is not perfect.”
Dr. Baggerly stressed that data consumers should not hesitate to ask if an independent research group has been able to replicate the findings. If another group hasn’t yet reproduced the work, oncologists interested in the results should ask if the original research team road tested their predictive model by running it on a completely blinded--and previously unseen--sample set.
The idea of holding back a data set and keeping it completely unavailable to model developers for a final road test is not new, Dr. Irizarry noted. “There is a long history of computer scientists and statisticians doing this sort of prediction” in which they take a numerical score of RNA expression or something else and predict an outcome, such as whether a person has cancer or how long they will live.
“For example, the postal service relies on zip code readers that evaluate black and white markings on paper and predict what number they represent. And in a more recent instance, Netflix, the movie rental company, held a contest with a $1 million prize for anyone who could develop a model that could predict what movie a particular viewer would like more accurately than their in-house model. In each case, the developers had access to one set of data for development and internal validation, and the judges held back a data set, completely unavailable to the developers, for external validation.
Perhaps, he said, medical regulators should use a simple bar when evaluating new predictive tests. “Until you show you can do it; you don’t use it,” Dr. Irizarry said. “This is not a new problem. It has been around for a while and it is doable.”

Multiple Layers
The problems that led to the overwhelming acceptance and use of both the ovarian cancer data--which no one thinks has any hint of misconduct--and the Duke data, involved multiple layers, beyond just the study authors. Dr. Brawley noted that the community used to be able to rely on the author’s institution to oversee the quality of work. “But now, in the current age, when people are patenting research and every university has an office of intellectual property, the university, which is supposed to police and supervise the investigator and make sure they are doing things properly and with integrity, has a conflict of interest.”
In addition, financial interest on the part of the researchers could lead to errors as they hurry to claim intellectual property rights. “There can be a tendency to rush, and to get sloppy as one rushes to get a product or finding,” he said. “I really think our attempt to do this quickly and our attempt to do this with some secrecy, with proprietary nature to it--that is what is hurting us.”
Critics also point out that the journals that published the Duke data have been slow to react to the scientific concerns. Drs. Baggerly and Coombes sent letters first to the investigators themselves and, when the errors were not rectified, then to Nature Medicine, Lancet Oncology, and the Journal of Clinical Oncology, which published the work. Nature Medicine published their letter, but the other two journals chose not to, despite their scientific basis.
“That is one of the things that was problematic about this,” Dr. Irizarry explained. “For me, as a statistician working in the trenches with this type of data, as soon as I saw [Drs. Baggerly and Coombes’] talk, it was clear to me that they were complaining about something that was fundamental and important. It was a little surprising to me that the journals did not ask for clarification or retract the paper.” The Lancet published an “expression of concern” in July of this year, but only after the problems with Dr. Potti’s resume were discovered.
Meanwhile, Dr. Brawley says that the problems with the Duke experiments and Dr. Potti’s resume are unlikely to alter the way ACS funds or evaluates grants in a major way. “It has been rare that we’ve been burned,” he said. “We encourage open conversations, but won’t likely change how we give out grants--though we might go on the internet and search the Rhodes scholars.”
As for Dr. Baggerly, he says that he doesn’t plan on doing another intensive project on another group’s data. But if the data are clinically important and he gets requests from MD Anderson clinicians to use the technique, he might. “If you make dramatic claims that have clinical relevance such that several investigators at MD Anderson want to do it--if it is that important--then you should be prepared that people want to check it and check it closely,” he said.
“I am hopeful that the next time this happens I will be in the position of saying ‘Wow this works. We should be using this tomorrow.’ That would be nice.”

credit for finding this article: factchecker
Edited by chatham, Aug 23 2010, 06:36 PM.
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MikeZPU

Quote:
 
In the second category, Dr. Baggerly says that the Duke investigators said their data showed that expression of a particular gene, ERCC1, correlated with response to some agents. However, the commercial microarray chip the Duke investigators said they used in their experiments does not include that gene. “I admit this is one for which I do not have a simple, charitable explanation,” Dr. Baggerly told OT.


These researchers have very specific issues with Potti's data, well-founded with principled details.

Duke thought they could just blow these off?

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sceptical

Dr. Potti is quoted in this article published 8/19/10 about the ASCO meeting held in June:

http://www.inpharm.com/news/asco-2010-hedgehog-pathway-and-other-ways-target-cancer

Lung Cancer

A new targeted treatment for non small cell lung cancer has produced spectacular results in a sub-group of patients.

Pfizer’s crizotinib is in a new class of drugs that inhibit the ALK gene, which is thought to play a key role in a sub-set of non small-cell lung cancer (NSCLC) tumours.

Crizotinib produced a 90% response rate in NSCLC patients whose tumours had a rearrangement of the ALK gene, and who had failed two previous chemotherapies.

The phase II results were presented at ASCO and generated considerable excitement.

“This is stellar, compared with what we see in non selected NSCLC patients treated with chemotherapy,” said principal investigator Dr Alice Shaw, a thoracic oncologist at the Massachusetts General Hospital Cancer Center in Boston.

“This response rate is unprecedented in lung cancer,” Anil Potti, MD, associated professor of medicine at Duke University in Durham, North Carolina, told Medscape Oncology.

“This is a huge success for biomarker-driven clinical trials,” he added, saying he hoped the results would make tumour type tests the norm, and signal an end to testing drugs in unselected patient groups.

Crizotinib is now entering a phase III trial and a central laboratory is carrying out the lung cancer tissue genotyping.

The study was presented by Yung-Jue Bang, MD, from Seoul National University College of Medicine in Korea.

It was conducted in 82 patients with NSCLC who had the ALK fusion gene and who had progressed on previous chemotherapy regimens (a median of three).

More than 90% of patients showed tumour shrinkage, and responses lasted up to 15 months, and patients had a 72% probability of being progression-free at six months.

A phase III trial (PROFILE-1007) has already begun that is comparing crizotinib to standard second line chemotherapy.
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chatham
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Think about it. Starting a company that could tissue type specific cancers for directed treatment could be worth billions. Duke of course wants to be at the forefront. So brodhead defends bad and questionable science from someone who lied on his CV?

http://www.medscape.com/viewarticle/723075

Crizotinib in ALK-NSCLC; Response Rate "Unprecedented"
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