Suspicions Raised About Another Japanese Cardiovascular Researcher Reply

Significant questions about research misconduct have been raised about a prominent Japanese cardiovascular researcher, Issei Komuro.

Last year a Nature paper on which Komuro served as a co-author was corrected because “several images were mistakenly switched or duplicated during preparation of the artwork.” The Nature correction states that the “corrections do not alter any of the conclusions” of the paper. Now, however, a Japanese blog, entitled Issei Komuro – image manipulation -, raises questions about 13 additional papers. The papers were all published in well-known journals, including a second Nature paper, Nature Medicine, and 4 separate papers in Circulation. On many of the papers Komuro served as the senior author.

Click here to read the full post on Forbes.

 

 

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Scrutiny Of Sodium Meta-Analysis In Heart Uncovers Duplicated And Missing Data Reply

A meta-analysis published in the journal Heart has been retracted. As Adam Marcus writes in Retraction Watch, the retraction occurred when the journal editors learned “that two of the six studies included in the review contained duplicated data.  Those studies, it so happens, were conducted by one of the co-authors [of the meta-analysis].”

The article, “Low sodium versus normal sodium diets in systolic heart failure: systematic review and meta-analysis,” was published online in August 2012. In their attempt to investigate the duplicate data, the Heart editors reported “that the raw data are no longer available having been lost as a result of computer failure.”

The authors of the meta-analysis were James J DiNicolantonio (Wegmans Pharmacy, Ithaca, NY), Pietro Di Pasquale (Chief Division of Cardiology, “Paolo Borsellino”, G.F. Ingrassia Hospital, Palermo, Italy),  Rod S Taylor (Peninsula Medical School, University of Exeter, Exeter, UK), and Daniel G Hackam (University of Western Ontario and the London Health Sciences Centre, London, Ontario, Canada).

It was the second author, De Pasquale, who was the co-author of the duplicated papers that also contained the missing data.

You can read the entire story in Retraction Watch. Don’t miss the comments. Here’s one:

“computer failure” is the scientist’s version of “the dog ate my homework”

 

heart cover may13

Japanese Research Scandal Expands To A Second Trial And A Novartis Employee Reply

A Japanese research scandal, which has so far centered on actions taken by the once-prominent cardiologist Hiroaki Matsubara, has now expanded. As has been previously reported, several papers authored by Matsubara have been retracted, including, most notably, the main publication of the Kyoto Heart Study in the European Heart Journal.

Now, however, questions have been raised about  another clinical trial, the Jikei Heart Trial, which was published in the Lancet in 2007.  (Matsubara was not involved in this trial.) Novartis, which manufactures valsartan (Diovan), the drug studied in both trials, has announced that it is investigating both trials in response to new allegations that a Novartis employee worked on the trials without any disclosure of his company affiliation.

Click here to read the full story on Forbes.

A Closer Look At A Case Of Duplicate Publication In JACC 2

English: http://en.wikipedia.org/wiki/Linda_an...

The Journal of the American College of Cardiology has published a Notice of Duplication about a review article written by a respected European cardiology researcher who has played a central role in the development of fractional flow reserve (FFR). The brief statement from JACC provides few details and could lead to various interpretations, but a further investigation suggests that the story may be fairly simple.

The notice states that a 2012 review article by Nico H.J. Pijls and Jan-Willem E.M. Sels, Functional Measurement of Coronary Stenosis, “duplicates to a considerable extent both the text and figures of a prior article,” Fractional flow reserve: a review” published in 2008 in Heart, by two different authors, Bernard De Bruyne and J. Sarma. Here is the JACC editors explanation:

Dr. Piljs attributes this duplication to the close collaboration that he has had over many years with Dr. De Bruyne, and the fact that both authors drew text and figures for these reviews from the same repository of material used for a joint educational program. He acknowledges his lack of care in the preparation of the manuscript and apologizes for the duplication. While the Editors accept this apology, we lament the replication of information that prevented the pages devoted to Dr. Piljs’ article from being filled with new material.

De Buyne and Pijls are longtime colleagues who have played a central role in the development of fractional flow reserve, serving as principal investigators of the seminal FAME and FAME II clinical trials. I asked them for a response to this situation. Here is their statement:

The cryptical phrasing “repository of……..” is not ours, but made by JACC.

The “repository” they mean is a keynote lecture from the bi-annual Aalst-Eindhoven-Course on Coronary Physiology, which we organize once or twice a year in Brussels since 2001. The Course is endorsed by the European Society of Cardiology and has been organized by us already 17 times.

The opening lecture of that course (keynote lecture) is always entitled: ”Practice and advanced applications of Coronary Pressure Measurement” and alternatively given by Dr de Bruyne and Dr Pijls.

That lecture has been built up by us and developed carefully over the years and has been streamlined for optimum educational content and benefit, including phrasing and slides.Not a single word is not ours.

The slides are always distributed among the participants and used by many of them for their own lectures or presentations or any educational purposes. In fact , they are public domain. Consequently, we have seen (parts of) our text and slides been used by others a myriad of times and are proud to have contributed to the dissemination of valuable medical knowledge.

When Dr De Bruyne wrote his review for HEART in 2008 , he used that keynote lecture as the basis of his paper.

When Dr Pijls wrote his State-of-the-Art paper ( i.e also a review) on the invitation of JACC in 2012, he also used text and slides of that keynote lecture (extended in the meantime) without realizing that Dr De Bruyne had done the same some years earlier. As a result, the first part of Dr Pijls paper is very close to Dr De Bruyne’s review, wheras the second part of Dr Pijls paper reflects the new data and insights obtained in those last 4 years.

So, there is nothing mysterious about that “repository” and we explained this to JACC in a similar way as we do now to you.

And by the way, when Dr Pijls submitted his paper to JACC, he mentioned explicitely in the submission letter that – as the nature of this paper was a State-of-the-Art paper – it was a concise reflection of the knowledge in the field and not original data.

Answering your last question: Neither Dr De Bruyne nor Dr Pijls ever received any financial or other compensation from whoever or in whatsoever way for writing any of these papers.

Writing these papers was on the strict invitation of the editors of Heart and JACC respectively and except the authors and staff of the Journals, nobody was even aware of it before they were published.

And as stated above: any single word or figure in any of these papers is completely our own work to which we equally contributed.

Comment: When I first read the notice it seemed to me like the case was an indication of a larger wrongdoing. I’m glad my initial suspicions were proven wrong. This is a great example of why editor’s notes should be much more detailed. The truth needs to come out no matter which way it falls.

Scientific Misconduct: From Darwin And Mendel To Poldermans And Matsubara Reply

Responding to recent episodes of scientific misconduct in cardiovascular research involving once prominent cardiovascular researchers, the editor of the European Heart Journal, Thomas Lüscherhas written an editorial discussing the significance of the new cases and placing them in a historical context that includes allegations of scientific misconduct by Mendel and Darwin, among many others.

Poldermans was the first or the senior author in 7 papers published in EHJ. Lüscher writes that the chairman of the Poldermans investigative committee “made it clear that the vast amount of publications led by Poldermans over the last decades made it impossible to assess their scientific validity in all cases.” As a result, Poldermans announces that “the editors of the European Heart Journal therefore would like to make an expression of concern related to the papers where Poldermans was the responsible author.”

Comment: Without more information there will continue to be a large cloud of uncertainty hanging over the cardiovascular literature. The statement of the chairman of the Poldermans committee bears repeating: “the vast amount of publications led by Poldermans over the last decades made it impossible to assess their scientific validity in all cases.”

 Click here to read the full story on Forbes.

 

Gregor Mendel
Gregor Mendel

 

Don Poldermans

 

 

 

 

Embers Of Poldermans Case Still Smoldering Reply

Poldermans

Don Poldermans

A prominent US cardiologist has rebuked Don Poldermans, the cardiovascular researcher at the center of a research scandal in the Netherlands. As reported here previously, Poldermans was fired for scientific misconduct by the Erasmus Medical Center in Rotterdam, where he had been a professor of medicine and the head of perioperative cardiac care. He was widely published and active in the field, serving as a member of the European Society of Cardiology committee for practice guidelines and as the chairperson of the ESC guidelines on pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. He was also the lead author of the influential (but controversial) 1999 New England Journal of Medicine DECREASE study on the use of bisoprolol during vascular surgery. An investigation at Erasmus found that Poldermans used patient data without written permission, used fictitious data, and submitted two reports to conferences which included knowingly unreliable data.

The new episode has its origins in a review article published last October by prominent cardiologist University of Michigan cardiologist Kim Eagle, and a colleague, Vineet Chopra, in the American Journal of Medicine. The article, “Perioperative Mischief: The Price of Academic Misconduct,” discusses the “caustic” effects of the Poldermans case, noting the dilemma facing clinicians “now that a considerable portion of the literature is enshrouded in uncertainty.” Now (as first reported by Retraction Watch) Poldermans and the Michigan cardiologists have exchanged letters in the April issue of the journal.

In his letter responding to Eagle and Chopra’s review article, Poldermans is critical of the Michigan authors for accusing him of “scientific fraud.” Poldermans acknowledges in his letter that he made various mistakes, including failure to obtain written informed consent and “negligent” data collection. He denies, however, that he fabricated data or published any results based on the compromised data. He writes that Eagle and Chopra assumed he was guilty despite the fact that the final report from the Erasmus Medical Center had not been released. He notes that in the final report Erasmus had concluded that “no evidence was found for any manipulation of the research results by the researchers in the sense of deliberate steering of results into a particular direction.”

In their response, Eagle and Chopra said that in their article they had stated that the accusations of fraud were still allegations. More importantly, Poldermans missed the larger point of their paper:

Click here to read the full story on Forbes.

Kim Eagle

Kim Eagle

 

 

 

European Heart Journal Retracts Main Paper Of The Kyoto Heart Study 1

The editors of the European Heart Journal have retracted the 2009 paper reporting the main results of the Kyoto Heart Study, a randomized, open-labeled study testing the add-on effect of valsartan to conventional therapy in high-risk hypertension. The retraction notice gave no details about the problems that led to the retraction. Here is the full text of the retraction notice:

“This article has been retracted by the journal. Critical problems existed with some of the data reported in the above paper. The editors of the European Heart Journal hereby retract this paper and discourage citations of it.”

Click here to read the full story on Forbes.

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JACC Issues Notice of Concern Over Three Poldermans Papers 1

The editors of the Journal of the American College of Cardiology have issued a “Notice of Concern“ over three JACC articles in which Don Poldermans, the disgraced Dutch researcher, served as the first or the last author. The editors relied on the report of the investigation committee at Erasmus Medical Center published in October. In each case the editors have accepted the committee’s finding that although the studies contain numerous examples of scientific “irregularities,” the evidence does not warrant full retractions for the papers.
jaccFor the first paper, the committee cited numerous irregularities, including  inconsistencies between source documentation and the Case Report Forms and “an unreliable working procedure for collection of scientific data.” But the committee also found no “evidence for any manipulation of the research results by the researchers in the sense of deliberate steering of results into a particular direction” or that “the research conclusions as published in the above mentioned article are wrong.” “It is impossible,” the editors write, for them “to determine the effect of this breach of scientific integrity upon the overall conclusions of the manuscript.”
For the second study, the committee expressed “doubt about the validity of the causes of death recorded in the data base.” The lack of  source documentation is “unfortunate” but the editors, like the committee, “could not determine how these facts influenced the conclusions of the manuscript.”
For the third study, the committee found negligence relating to informed consent, preservation of case report forms, and data collection. Although the committee was “unable to vouch for  the reliability of the findings” the editors, once again, “could not determine with certainty that the findings of the study were erroneous.”
Here is the conclusion of the editors’ notice of concern:

Since it is not possible for the Editors of JACC to determine with certainty that the findings in the above articles were erroneous, we have elected not to retract these manuscripts. However, given the uncertainty regarding the accuracy of the data, and the inability to validate the collection of data, readers should be cautioned in the application of the findings of these manuscripts to clinical practice.

Hat tip: Marilyn Mann

Yet Another Look At The Transcendental Meditation Paper 84

Editor’s note: Below are two responses to Robert Schneider’s defense of his Transcendental Meditation paper, which Schneider wrote in response to my earlier article about the publication of his paper.  In the first part I respond to some of the general issues raised by Schneider. The second part, from Sanjay Kaul, addresses the statistical issues discussed by Schneider.

I’m grateful for Kaul’s highly technical analysis of the statistical issues raised by Schneider, but I don’t think this case really requires a terribly high level of technical expertise. Common sense actually works pretty well in this case. A trial with barely 200 patients can not be expected to provide broad answers about the health benefits of a novel intervention. As Kaul and others have stated on many other occasions, “extraordinary claims require extraordinary evidence,” and it is quite clear that the evidence in this trial is not extraordinary, at least in any positive sense.

Questions About Trial Reliability And Data– In his response Schneider tries to skate away from the inevitable questions raised about this paper when Archives of Internal Medicine chose to withdraw the paper only 12 minutes before its scheduled publication time. Schneider can pretend that this incident never occurred, but outsider readers can not help but wonder what sparked this extraordinary incident, and will not be satisfied  until the details are fully explained.

There are additional red flags about the trial. Schneider told WebMD that since the Archives incident “the data was re-analyzed. Also, new data was added and the study underwent an independent review.” Said Schneider:

“This is the new and improved version.”

This is an extraordinary claim, because a clinical trial can not be “new and improved” unless there were serious flaws with the earlier version. What exactly does it mean to say that a paper published in 2012 about a trial completed in 2007 is “new and improved”? (According to ClinicalTrials.Gov the study was completed in July 2007, while June 2007 was the “final data collection date” for the primary endpoint.)
Click to continue reading…

Investigator Defends Controversial Transcendental Meditation Paper 3

Editor’s Note: Here is a response by Dr. Robert Schneider to my story last week about his controversial paper on Transcendental Meditation that appeared in Circulation: Cardiovascular Quality & Outcomes. I will respond to Dr. Schneider’s post later this week.

Response from Dr. Robert Schneider

We appreciate the interest in our article published in Circulation: Cardiovascular Outcomes and Quality, November 2012.  However, there are several errors and inaccuracies in the blog. Many of these points were addressed in the Circulation Outcomes publication.  Below are highlights.

Robert Schneider, MD, director of the Institute for Natural Medicine and Prevention and dean of Maharishi College of Perfect Health in Fairfield, Iowa. Courtesy MAPI

1.     This was a prospective, randomized, controlled, single-blinded clinical trial.  This report is the first publication of data from the trial. It was revised in response to extensive peer-review over the past months.  Whatever unpublished version of the manuscript the bloggers had access to previously did not have the benefit of the most current peer review and revision.

2. There were a range of check and balances built into the study to ensure veracity.  For example:

  • data were collected blindly at the clinical site in Milwaukee
  • the trial was monitored by independent data safety and monitoring board
  • end point events were adjudicated by an independent reviewer using standardized criteria
  • results were confirmed by independent data analysis
  • limitations are enumerated and discussed in the publication

3. Regarding the hypothesis testing capacity of the study, according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines,

“Randomised clinical trials (RCTs) are generally considered to produce the most solid evidence for the effectiveness of medical interventions”  (Keech 2007).  The CONSORT guidelines are recommended by the International Committee of Medical Journal Editors (ICMJE). The design, implementation, analysis and reporting of this trial followed CONSORT guidelines.  Thus this clinical trial was an experimental study that tested an hypothesis.  By contrast, observational studies, which this was not, generates hypotheses (http://en.wikipedia.org/wiki/Observational_study).

4.  The total number of primary end point events is within one of an earlier, unpublished version of the manuscript (noted in blog update November 18).  In preparation for the revised manuscript, one additional event was identified.  However, this had no meaningful effect on the results or statistical significance. That is, the main results are essentially unchanged.
Click to continue reading…

Mysterious Disappearing Paper Finally Reappears In Another Journal 33

Robert Schneider, MD, director of the Institute for Natural Medicine and Prevention and dean of Maharishi College of Perfect Health in Fairfield, Iowa. Courtesy MAPI

Updated– Last year, in what may have been an unprecedented action, a paper on the effects of Transcendental Mediation (TM) in African Americans was withdrawn by the editors only 12 minutes before the paper’s scheduled publication in Archives of Internal Medicine. No definitive explanation was ever provided, though the editors and authors said that the action was prompted by last minute questions from reviewers at the NIH, which helped fund the study. (The episode was covered in detail on CardioBrief  (here and here) and on RetractionWatch.)

Now a new version of the paper has been published in Circulation: Cardiovascular Quality & Outcomes. The first author is Robert Schneider, from the Institute for Natural Medicine and Prevention at Maharishi University of Management in Maharishi Vedic City, Iowa. The co-authors are from the same institution and from the department of medicine at the Medical College of Wisconsin in Wisconin. It is clearly the same study of 201 African American patients randomized to TM or health education (HE) and followed for 5.4 years, though some of the numbers have changed in important ways between the earlier and later publications. One change involves the primary endpoint: the new paper in Circ:CVQ&O reports  52 primary endpoint events (the composite of death, MI, or stroke). Of these, 20 events occurred in the TM group and 32 in the HE group. By contrast, in the previous Archives version there were 51 primary endpoint events: 20 in the TM group and 31 in the control group.

In both papers the difference in the primary endpoint did not achieve statistical significance until after the investigators adjusted for baseline differences. The unadjusted hazard ratio (HR) for the new study was 0.64, (confidence interval 0.3701.12, p = 0.12); after adjusting for age, gender, and lipid lowering medications the HR drops, presto-chango, to 0.52 (0.29-0.92, p=0.025) and achieves statistical significance..

Dome shaped building on MUM campus, for the group practice of the TM-Sidhi program and Yogic Flying (Photo credit: Wikipedia)

Here are some other key questions that I have asked AHA, Circulation editors, and other experts to address:

– Was the AHA or the Circulation staff aware at any time that an earlier version of this paper had been scheduled for publication in Archives of Internal Medicine and withdrawn only 12 minutes before the scheduled publication time? Should this information have been disclosed by the study authors when submitting the paper?

– As mentioned above, the original publication in Archives appeared to have been cancelled because of questions raised by NIH reviewers. Have the Circulation: Cardiovascular Quality & Outcomes editors received any assurance that these questions have been addressed in the new paper?

– This trial was started all the way back in 1998 but was not registered on ClinicalTrials.Gov until February 2011 (shortly before the intended Archives publication). Why was it not registered earlier than 2011?

– June 2007 is listed in ClinicalTrials.Gov as the final data collection date for primary outcome measure. Why are the primary endpoint numbers different between the Archives and new version of this paper?

Update, November 13-Harlan Krumholz, the editor of  Circulation: Cardiovascular Quality & Outcomes, sent the following statement:

“We had no prior knowledge of what transpired with the Archives of Internal Medicine.  The Schneider paper went through rigorous peer review, statistical review and editorial discussions and the authors of the article were responsive to the review process.  As a result, the paper was accepted for publication and we are going ahead as planned.  If you have any further questions, we suggest you contact the researchers directly.”

Update, November 18–  An earlier version of this article contained several mistakes. First, the difference in the number of primary endpoint events between the two papers is much smaller than I had stated. The original paper reported 51 primary endpoint events. The new paper reports 52 endpoint events. I am still unclear about why there should be any difference between the two, since, as mentioned above, June 2007 was the final data collection date for the primary endpoint. I also incorrectly claimed that some  data reported in the original Archives paper were not included in the new paper. In fact, as a reader pointed out in the comments section below, these data were reported in Figure 1. I apologize for this mistake and regret the error. –LH

I asked Sanjay Kaul for his perspective on the paper. Here are his points:
Click to continue reading…

Nine Italian Cardiologists Arrested In Broad Investigation Of Research Fraud And Misconduct 2

The Arrest of Maria Grazia Modena, from Il Resto Del Carlino

Nine Italian cardiologists have been arrested as part of a broad investigation into serious medical misconduct at Modena Hospital, according to multiple reports in the Italian media. The investigation encompasses at least 67 other individuals and a dozen medical equipment companies, including 6 foreign companies. The charges include conspiracy, fraud, embezzlement, bribery, forgery and performing unauthorized clinical trials. Several news reports mentioned that stents and angioplasty balloons were involved.

According to one Italian website, the investigation started in 2011 in response to allegations by a group, Amici del Cuore (Friends of the Heart), that patients at the Modena Hospital (Policlinico di Modena) received treatments and procedures as part of unauthorized experiments. In some cases the procedures may have resulted in fatal outcomes. The accused physicians ”performed experimental tests without making it known to patients for the sole purpose of writing about these trials in specialized magazines collecting money through bogus non-profit organization,” the website reported. [All translations in this story taken from Google Translate.]

“We wanted to ask questions about certain procedures that went far beyond the standard ones, and that seemed unusual to us,” the president of Friends of the Heart, Professor Giovanni Spinella, told Il Salvagente. “We were aware that invasive procedures were performed, often on peripheral organs, and sometimes had little to do [with] the heart. And unfortunately had caused discomfort and damage to several patients.”

Another Italian site quoted a police official who called it “a major operation” and said the accused “committed human clinical trials without authorization and installed medical devices and equipment defective in patients unaware of being subjected to an experimental treatment.” The accused physicians then “created false medical records to cover medical errors.” The Italian media said the investigation included recordings of telephone conversations between the suspects. The Italian police named the operation camici sporchi (“dirty gowns”).

The most prominent person arrested was Maria Grazia Modena, the chief of cardiology at Modena Hospital and a former president of the Italian Society of Cardiology. (Grazia Modena was the subject of a profile in Circulation European Perspectives (PDF) in 2007.) Modena, 60 years old, was trained partly at New York University and the Mayo Clinic. The second main focus of the investigation appears to be the head of the catheterization laboratory at the hospital, Giuseppe Sangiorgi. According to news reports, he is the only arrested physician who is still in jail.

Here are the names of the nine physicians:

  • Maria Grazia Modena, chief of cardiology
  • Giuseppe Sangiorgi, head of the catheterization laboratory
  • Luigi Vincenzo Politi
  • April Alexander
  • Simona Lambertini
  • Giuseppe Biondi Zoccai
  • Fabrizio Clement
  • Alessandro Mauriello
  • Andrea Amato, 36

Don Poldermans And The Dutch Research Scandal 4

The publication last week of the final report from the Erasmus Medical Center on the Don Poldermans research scandal in the Netherlands ends the first and most explosive chapter of an ugly episode of scientific misconduct. But there are still many important questions regarding scientific integrity and the culture of medical research raised by the case. And one key detail about the case remains– and is likely to remain– unanswered. Did Don Poldermans commit scientific fraud by fabricating data or was he only guilty of the serious but lesser sin of poor or negligent supervision of a research factory?

The final report on the Poldermans affair from his former institution and employer, Erasmus MC, accuses him of serious scientific misconduct, including:

  • “failure to preserve essential source documentation,”  so that “further verification and analysis ” is now impossible;
  • “failure to record actual medication use, in a study focusing on an intervention using medicines”; and
  • failure to obtain informed consent, or to do so improperly.

The most serious accusation is that “fictitious data” was used in one study, “a serious breach of academic integrity.” However, this accusation does not appear to be rock solid, since it is based on disparities between the study data and a database examined by the committee. However, Poldermans claims that the database examined by the committee was provided to them by the whistleblower (a fellow in his laboratory) who did not have access to the original database (which Poldermans claims was destroyed) and was not the database used in the study. It’s unlikely that the full truth about this will ever be known. Poldermans says that the committee’s conclusions were “suggestive, speculative and often even demonstrably false.”

In an hour-long interview with me during the recent ESC meeting in Munich, Poldermans talked a great deal about the case, accepted responsibility for the less serious charges but adamantly  denied the more serious charges. Poldermans, who is now working as a vascular medicine physician at a non-teaching hospital, said he has no expectation of ever regaining his former position or resuming research: “that’s something I can accept, but I can’t accept that people would think I faked patients or that patients were hurt,” he told me.
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Erasmus Medical Center Releases Final Report On Cardiovascular Research Scandal 2

After an extensive investigation, a large medical center in the Netherlands has confirmed earlier charges of research misconduct against a prominent cardiovascular researcher. On Tuesday, Erasmus MC in Rotterdam released a final report on the scientific integrity of trials conducted by Don Poldermans, a well-known and highly prolific Dutch cardiovascular researcher. The final report contains numerous allegations of scientific misconduct related to the conduct of several clinical trials run by Poldermans at Erasmus MC.

Poldermans admits responsibility for some instances of misconduct but also vigorously denies the most serious charges involving scientific fraud. He provided CardioBrief with detailed written responses to the charges and also presented a spirited defense during an exclusive interview conducted in August during the ESC meeting in Munich.

In a statement to the press, Erasmus MC said that the new report confirms the earlier suspicions raised in the case, which ignited a firestorm of conroversy in the Netherlands last winter. The press statement mentions”serious shortcomings” in obtaining informed consent for patients enrolled in studies and the submissions of “unreliable data” based on “scientifically inaccurate data collection.” Poldermans and Erasmus MC are in full agreement, however, that the misconduct “did not lead to health damage to patients.”

In a statement prepared for CardioBrief in response to the report, Poldermans apologizes for his “administrative carelessness” and accepts full responsibility for the missing consent forms. He accepts the “extreme consequence”–  his dismissal from Erasmus MC–  over this issue, but emphasizes that no harm occurred to any of the patients and, further, that no additional or unnecessary treatments or diagnostic procedures took place. He vigorously denies any larger scientific misconduct or fraud.

The committee report — and Poldermans defense — are often highly technical, and the report is based on incomplete and inconsistent information obtained by the investigating committee at Erasmus MC. One problem is missing data. Investigators scrutinizing Polderman’s work have been unable to find the case files and other documentation for some patients in the trials. Consequently, the report raises concerns about possible data fabrication. Poldermans strongly denies this suggestion and states that he properly stored all the files at Erasmus MC. His defense is that some records were damaged by water and some records disappeared when the hospital itself threw out boxes of documents stored in the archives.

Poldermans had been a professor of medicine and the head of perioperative cardiac care at the Erasmus Medical Center. He was widely published and active in the field, serving as a member of the European Society of Cardiology committee for practice guidelines and as the chairperson of the ESC guidelines on pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. He was also the lead author of the influential 1999 New England Journal of Medicine DECREASE study on the use of bisoprolol during vascular surgery. Poldermans now works as a vascular medicine physician at a nonteaching hospital in the Netherlands.

CardioBrief will publish a followup story in the near future based on an interview with Poldermans conducted in Munich during the ESC.

Related Links:

New Perspective on the Dutch Cardiovascular Research Scandal Reply

New information and details have  emerged about the cardiovascular research scandal in the Netherlands. One prominent cardiologist with close ties to the central character in the scandal has been cleared of wrongdoing by his institution and a feature magazine article sheds new light on that central character, Don Poldermans.

As previously reported here last November, Poldermans was fired for scientific misconduct by the Erasmus Medical Center in Rotterdam. Poldermans had been a professor of medicine and the head of perioperative cardiac care at the Erasmus Medical Center. He was widely published and active in the field, serving as a member of the European Society of Cardiology committee for practice guidelines and as the chairperson of the ESC guidelines on pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. He was also the lead author of the influential (but controversial) 1999 New England Journal of Medicine DECREASE study on the use of bisoprolol during vascular surgery. An investigation at Erasmus found that Poldermans used patient data without written permission, used fictitious data, and submitted two reports to conferences which included knowingly unreliable data.

A few weeks after the Poldermans affair became public, another medical center in the Netherlands, Leiden University Medical Center, announced that it was conducting its own investigation specifically looking at “a professor who had published frequently” with Poldermans. Although no names were publicly disclosed, it subsequently became clear that the primary focus of the investigation was Jeroen Bax, a cardiologist at LUMC who had co-authored more than 350 papers with Poldermans. Bax is an ESC board member and the chairman of the ESC guidelines committee.

LUMC has now completed its investigation and concluded that no “scientists at the Leiden University Medical Centre [were] involved in the violation of academic integrity by” Poldermans. However, the investigation also expressed concern about the large number of papers co-authored with Poldermans by LUMC scientists.

A feature article in the Dutch language publication Medisch Contact provides a much more detailed portrait of Poldermans and fills in much of the background of the entire affair.

Following the initial media storm last fall, the subsequent silence has been received with gratitude by Poldermans. Although he refused to give Medisch Contact an interview, in a phone conversation with the publication he said that he is “happy with the radio silence and that “it is the only way to survive.” He said he’s looking for a new job and expects to find one shortly.
Click to continue reading…

Prominent Japanese Cardiologist Accused of Scientific Misconduct 3

Following accusations by independent bloggers in Japan and Germany, the American Heart Association (AHA) has issued an Expression of Concern about five papers published in AHA journals co-authored by Hiroaki Matsubara, a prominent cardiologist and researcher at Kyoto Prefectural University in Japan. In addition to his many papers exploring the basic science of the renin-angiotensin system, Matsubara was the chief investigator of the KYOTO HEART Study, a randomized, open-labeled study studying the add-on effect of valsartan to conventional therapy in high-risk hypertension.

Questions about Matsubara’s work were initially raised last year on a Japanese blog and then pursued in three English language posts (herehere and here) on a German site, the Abnormal Science Blog. Abnormal Science reported evidence of serious scientific misconduct in 12 papers in which Matsubara was the only common co-author. The AHA posted its Expression of Concern on Monday, which was subsequently reported by Retraction Watch.

The three posts on Abnormal Science demonstrate repeated examples of  image manipulation and copying, as well as self-plagiarism. The non-AHA journals cited by Abnormal Science include Kidney InternationalBiochemical and Biophysical Research Communications, and Journal of Molecular and Cellular Cardiology. At least one paper, in Molecular and Cellular Biochemistry, has been  retracted “due to a mistake of duplicating the publication of original data” that already had appeared in Circulation Research. Here is how Abnormal Science summarized its initial findings in several of the papers:

It is apparent that band images from ‘real’ blots may have been digitally reassembled into new blot images pretending to be derived from distinct experimental settings. Since ‘reconfigured blots’ have been densimetrically scanned and the results illustrated in tables and figures, we are presumably confronted with a case of severe data fabrication.

These are the five papers cited by the AHA, including the number of citations as reported by Retraction Watch:

Japanese Researcher With Harvard Connections Retracts 3 Articles in AHA Journals 1

Akio Kawakami, a well published lipid researcher at Tokyo Medical and Dental University, has retracted 3 papers from AHA journals, including one article in AHA’s flagship journal Circulation. News of the retractions was first reported on Retraction Watch.

Two of Kawakami’s co-authors are well known researchers affiliated with Harvard University and the Brigham and Women’s Hospital, Peter Libby and Frank Sacks. Prior to his position in Tokyo, Kawakami had been at the Harvard School of Public Health in the Department of Nutrition, where Sacks also works. Sacks is a co-author on all three of the retracted papers, while Peter Libby is a co-author on one of the retracted papers. Kawakami was also the first author of 4 other papers on which Libby and Sacks were co-authors, including two papers published in 2006 in Circulation (here and here).

Donna Arnett, the incoming president of the AHA, told CardioBrief that the retractions were requested by Kawakami himself. She said he initially contacted each of the individual journals, which then informed the AHA’s scientific publishing committee. (Arnett is a former chair of the committee.) “In this case it was the author himself coming forward, so it was fairly straightforward,” said Arnett. The retraction was then coordinated with the three journals.

Here are the 3 retractions:
Click to continue reading…

Resveratrol and Fraud 2

Last week a new case of scientific misconduct came to light. University of Connecticut resveratrol researcher Dipak Das was accused of serious scientific misconduct. (You can read my brief post about the case or, for all the gory details, you can follow the story on Retraction Watch.)

In this post I’d like to make two fairly simple points about the case:

1. Resveratrol and Fraud, the Bigger Issue

As far as we now know, this case of scientific misconduct occurred in the lab of one researcher with, at best, a modest reputation in his field. I don’t mean to suggest that the case should not be taken seriously, but it is  unclear whether it has any impact at all on the larger body of scientific research involving resveratrol and related areas. (It’s also possible that Das is only the first of dozens of rotten eggs yet to be discovered in this embryonic field.)

On the other hand, the case offers a great example of the far-reaching and dangerous fraud that so often supports the multi-billion dollar supplement industry. Because resveratrol is considered a nutritional supplement for regulatory purposes it is not subject to the rules and regulations that restrict the marketing of drugs. But, of course, all sorts of highly dramatic medical claims are made for these products. Here’s what Bill Sardi, the president of a company that makes Longevinex, a resveratrol product, claimed about reveratrol, in a statement distributed to media (attached below):

Resveratrol is an antidepressant, an anti-inflammatory, an anti-bacterial, anti-fungal, anti-viral, anti-cancer, cholesterol-lowering, liver-cleansing, brain enhancing molecule.  If Americans embraced resveratrol pills en masse, many prescription drugs would not be needed.

I’m not going to bother refuting this absurd statement. Instead I’ll quote a 2011 review article published in PLoS One:

The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources.

(Fun fact: one of the co-authors of the PLoS One review article was Dipak Das.)

2. Western Blots

The above quote from Bill Sardi is part of a long, rambling, often contradictory and bizarre defense of Dipak Das and resveratrol (reprinted below). Again, I have no intention of engaging all his points– I hope that regular readers of CardioBrief have been inoculated against this sort of hokum. But I do want to make sure one point doesn’t achieve any traction. The key item in the UConn report is that Das repeatedly manipulated western blot images. Sardi first argues that the western blots aren’t important at all:

The alleged faulty tests in no way altered the outcome of his research studies.  The western blot test was only one of many tests used to draw scientific conclusions in published studies.

But then Sardi tries out several new explanations, in the course of a few sentences rapidly cycling through different perspectives on the western blots. First, he states that  the images weren’t altered. Then he acknowledges that they were in fact altered, but that these alterations are standard practice. Then he accuses the university of willfully ignoring this “fact.”

I asked Dr. Das directly, did he altered western blot images, or directed others in his lab to do so.  While his initial answer was no, meaning he had not fabricated or altered any scientific finding, altering western blot images are a common practice in laboratories for reasons other than deception.  The university chose to present their findings in a derogatory manner.  Dr. Das explains that editors at scientific publications commonly request researchers enhance faded images of western blot tests so they can be duplicated in their publications.  Western blot tests are frequently altered to remove backgrounds, enhance contrast and increase dots-per-inch resolution so they are suitable for publication.  This had been fully explained to university officials long before. [sic]

The entire statement strikes me as a great example of the pathology of someone desperately seeking to deny, refute or minimize an inconvenient truth. One statement– that editors ask researchers to “enhance” western blots–  requires an immediate response. I contacted a member of the National Academy of Sciences who has published hundreds, if not thousands of western blots during the course of his distinguished career. His response was clear and unequivocal: “manipulating images is considered tampering with data.” He then clarified:

It is one thing to change the dots-per-inch (resolution) to fit a publication’s requirements – that is not crazy. But enhancing contrast and removing background is something that seems to me to be unacceptable. I certainly emphasize to students that that is unacceptable.  I know of cases where students might try to ‘clean-up’ data this way and I can imagine that in some cases a PI may not realize this has been done. But I have never heard an experienced investigator claim that a journal has asked them to remove background from a blot.  Now, maybe that has happened — I cannot say —  but certainly NEVER to me.

Update: Tom Bartlett of the Chronicle of Higher Education talked to a number of experts in the field to determine the significance of Das’s work not the field. In addition, longtime blogger Derek Lowe posted a detailed dissection of Sardi’s statement. Both posts are worth reading.

Click here to read the statement from Bill Sardi…

Investigation in Poldermans Case Expands to Leiden University Medical Center 1

The investigation in the Dutch scientific misconduct case has now spread to the Leiden University Medical Center, according to media reports in the Netherlands. The case first came to public attention last month when the Erasmus Medical Center in Rotterdam fired  prominent cardiovascular researcher Don Poldermans. (Click here for previous CardioBrief coverage of the case.)

A spokesman for LUMC told the Dutch media that the investigation is specifically looking at “a professor who has published frequently” with Poldermans [according to Google Translate], but it may also investigate other Leiden scientists. No names have so far been publicly mentioned, though CardioBrief has identified a prominent academic cardiologist at LUMC who has published more than 350 papers with Poldermans.