Retraction Watch

Tracking retractions as a window into the scientific process

Retractions follow revelations of misconduct by diabetes biotech

with 4 comments

diabetes careSeveral months after a drug company cancelled development of a potential diabetes cure because it found evidence that a biotech they had recently acquired had committed misconduct in studies of the drug, two retractions of relevant studies have appeared.

The research involves DiaPep277, which, as Josh Levy explained here in September, “would cause the immune system to stop attacking beta cells,” the cells in the pancreas that produce insulin. But Hyperion Therapeutics, which had acquired DiaPep277 developer Andromeda Biotech in June, announced in September that it had

uncovered evidence that certain employees of Andromeda Biotech, Ltd., which Hyperion acquired in June 2014, engaged in serious misconduct, including collusion with a third-party biostatistics firm in Israel to improperly receive un-blinded DIA-AID 1 trial data and to use such data in order to manipulate the analyses to obtain a favorable result.

The retractions are both of papers published in Diabetes Care in May 2014. Here’s the notice for “Treatment of Recent-Onset Type 1 Diabetic Patients With DiaPep277: Results of a Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial:”

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted.

The article reports on the DIA-AID 1 trial, which examined the safety and efficacy of DiaPep277 to treat type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd.

On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the DiaPep277 program. As stated in the press release issued by Hyperion Therapeutics, “The company has uncovered evidence that certain employees of Andromeda Biotech, Ltd. … engaged in serious misconduct, including collusion with a third-party biostatistics firm in Israel to improperly receive un-blinded DIA-AID 1 trial data and to use such data in order to manipulate the analyses to obtain a favorable result” (2).

The corresponding author notified the journal about these issues and subsequently submitted the following statement, which was reviewed by the American Diabetes Association’s Panel on Ethical Scientific Programs and approved for publication by the editors of Diabetes Care:

“In view of the public statements by Hyperion Therapeutics [2] regarding alleged scientific misconduct, we, the authors of this statement, are retracting the above-cited article. This alleged misconduct included collusion with a third-party biostatistics firm to improperly receive unblinded trial data and to use such data in order to manipulate the analyses to achieve favorable results. We wish to emphasize that we were not involved in the assembly of the raw data or the alleged misconduct. Despite our request, we have not been provided with the evidence upon which the allegations were made. On 7 October 2014, Hyperion Therapeutics and Clal Biotechnology announced that they had agreed to suspend legal proceedings and to engage an independent third party to analyze data from both the recent clinical trial, upon which this article was based, and the current phase 3 clinical trial, which will be completed at the end of this year. We further expect the participation of an independent third party approved by the authors. Following disclosure of the results of such independent analysis of both completed studies, we will issue a follow-up statement.

“The following authors support the decision to retract the article: Itamar Raz, Anette G. Ziegler, Thomas Linn, Guntram Schernthaner, Francois Bonnici, Larry A. Distiller, Carla Giordano, Francesco Giorgino, Liat de Vries, Didac Mauricio, Vlastimil Procházka, Julio Wainstein, Irun R. Cohen, and Paolo Pozzilli.

“The coauthors who are/were Andromeda Biotech employees—Dana Elias, Ann Avron, Merana Tamir, Rachel Eren, Dana Peled, and Shlomo Dagan—were unavailable for comment and therefore are not part of this retraction process.

“This issue was reviewed by my institution. The funding agency, Andromeda Biotech, did not respond to our requests to review this matter.

“Respectfully submitted,

Itamar Raz, MD”

The paper has been cited seven times, according to Thomson Scientific’s Web of Knowledge.

The other retraction is for “Evaluation of Long-Term Treatment Effect in a Type 1 Diabetes Intervention Trial: Differences After Stimulation With Glucagon or a Mixed Meal:”

Evaluation of Long-Term Treatment Effect in a Type 1 Diabetes Intervention Trial: Differences After Stimulation With Glucagon or a Mixed Meal. Diabetes Care 2014;37:1384–1391. DOI: 10.2337/dc13-1392

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted.

The study described in this article uses data from the DIA-AID 1 trial on DiaPep277 to compare treatment effects in patients with type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd.

On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the DiaPep277 program. As stated in the press release issued by Hyperion Therapeutics, “The company has uncovered evidence that certain employees of Andromeda Biotech, Ltd. … engaged in serious misconduct, including collusion with a third-party biostatistics firm in Israel to improperly receive un-blinded DIA-AID 1 trial data and to use such data in order to manipulate the analyses to obtain a favorable result” (2).

The corresponding author notified the editors of the journal about these issues and subsequently submitted the following statement, which was reviewed by the American Diabetes Association’s Panel on Ethical Scientific Programs and approved for publication by the editors of Diabetes Care:

In view of the public statements by Hyperion Therapeutics [2] regarding alleged scientific misconduct, we, the authors of this statement, are retracting the above-cited article. This alleged misconduct included collusion with a third-party biostatistics firm to improperly receive unblinded trial data and to use such data in order to manipulate the analyses to achieve favorable results. We wish to emphasize that we were not involved in the assembly of the raw data or the alleged misconduct. Despite our request, we have not been provided with the evidence upon which the allegations were made. On 7 October 2014, Hyperion Therapeutics and Clal Biotechnology announced that they had agreed to suspend legal proceedings and to engage an independent third party to analyze data from both the recent clinical trial, upon which this article was based, and the current phase 3 clinical trial, which will be completed at the end of this year. We further expect the participation of an independent third party approved by the authors. Following disclosure of the results of such independent analysis of both completed studies, we will issue a follow-up statement.

The following authors support the decision to retract the article: Paolo Pozzilli, Itamar Raz, and Irun R. Cohen.

The coauthors who are/were Andromeda Biotech employees—Dana Peled, Dana Elias, Ann Avron, Merana Tamir, Rachel Eren, and Shlomo Dagan—were unavailable for comment and therefore are not part of this retraction process.

“This issue was reviewed by my institution. The funding agency, Andromeda Biotech, did not respond to our requests to review this matter.

“Respectfully submitted,

“Itamar Raz, MD”

That paper has been cited once.

Hat tip: Linda Miller

Comments
  • Dave Fernig December 30, 2014 at 1:36 pm

    This could get interesting – Hyperion Therapeutics presumably paid real money for what looks to have been massaged data. A clear danger area for those who make it up: you keep making it up, get patents, then a third party puts real money in and suddenly you are in trouble. This is one area where lawyering up is good. Another is when misconduct leads to clinical trials that endanger patients.
    I await developments with interest!

  • Conrad Seitz MD December 30, 2014 at 5:00 pm

    Yes, this could be very interesting. Actionable, even criminal activity is possible here. The urge to get a drug into extended testing up to Phase III, even if it’s never marketed, is too profitable to resist for some people. This is a potentially big field, an antidiabetes drug, given the prevalence of even type one diabetes in all populations…

  • EPH February 9, 2015 at 4:18 pm

    I’ve seen some researchers say that promising research is being left out in the cold due to lack of interest on the part of pharma companies in supporting it. But then we get episodes like this that make me wonder if it’s not a case of the pharma companies being gun shy about potentially investing in doctored data. Every T1 diabetic (or parent thereof, as I am) I know has been told we’re 10 years away from a cure… well, it’s been 6 years since I heard that, and stuff like this is disheartening. I get it that nothing happens without $$ but do researchers not comprehend that this sort of thing destroys the hopes of people who struggle day to day with a disease that leaves little margin for error?

  • fernandp pessoa November 15, 2017 at 6:04 am

    Senior author second retraction, penultimate author first retraction, Irun Cohen as penultimate author.
    (Senior author of paper below died 2004.
    http://www.weizmann.ac.il/immunology/sci/LiderPage.html )

    FYI: DiaPep277™ (the drug used in the retracted clinical studies) is a peptide analog of human hsp60. http://www.google.com/patents/WO2013128450A1?cl=en

    J Immunol. 2005 Jul 1;175(1):276-85.
    Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and inflammation.
    Zanin-Zhorov A1, Tal G, Shivtiel S, Cohen M, Lapidot T, Nussbaum G, Margalit R, Cohen IR, Lider O.
    Author information

    1
    Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

    https://pubpeer.com/publications/D4822C5126632BF20383B18167C15A#10

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