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Retraction Watch

Tracking retractions as a window into the scientific process

Nature Medicine retracts MS paper with ghost data by former GSK researcher

with 7 comments

naturemed1213Nearly six months after first expressing concern about the validity of a 2010 paper on multiple sclerosis, Nature Medicine has retracted the article for containing “erroneous” data — which in this case don’t seem to have existed, making them more fabricated than wrong.

The paper, “Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease,” came from a group led by Jingwu Zhang, who at the time ran GlaxoSmithKline’s Research and Development Center in Shanghai.

In June, the journal issued an expression of concern about the article after readers discovered problems with the data, as reported by Nature Medicine’s blog.

Here’s the retraction notice:

The above manuscript was authored by scientists from the GlaxoSmithKline (GSK) Research and Development Center in Shanghai, China, and a researcher from Baylor Medical College who later became a GSK employee. Following anonymous reports of inaccuracies in this study, GSK conducted an investigation into these allegations.

The investigation established that the data depicted in Figure 6 and in Supplementary Figure 7 were erroneously attributed to experiments at Baylor Medical College with blood cells from patients with multiple sclerosis. In fact, no data from experiments with blood cells from patients with multiple sclerosis and no data from experiments at Baylor Medical College were included in the paper. GSK has therefore concluded that the paper contains erroneous data and requests that it be retracted.

Nature Medicine wishes to acknowledge that the two graphs at the bottom left-hand corner of Figure 2a are identical and that this was an error introduced by the journal during the production of the article. Below are the correct graphs as submitted by the authors (Fig. 1).

All authors agreed to the retraction of the paper with the following exceptions and clarifications. Xuebin Liu and Stewart Leung declined to sign the retraction and stand by the conclusions of the paper. Chunxia Wang, Xia Qin and Limin Lu did not respond to Nature Medicine’s requests for comment on the retraction. Ji Wang, Lei Fang, Bing Wan, Jian Hong and Hongtao Lu could not be reached by the journal for comment on the retraction. However, Chunxia Wang, Xia Qin, Limin Lu, Ji Wang, Lei Fang, Bing Wan, Jian Hong and Hongtao Lu signed an initial version of the retraction submitted to the journal by GSK.

The glaring omission here is Zhang, but a spokesperson for Nature Medicine tells us he agreed to the retraction. The paper has been cited 74 times, according to Thomson Scientific’s Web of Knowledge.

Update 12/6/13, 11:00 a.m. Eastern: GSK has issued a statement regarding the study, which you can read here. It says, in part:

In June we concluded an investigation of the publication and, regretfully, established that certain data were indeed misrepresented. We shared our conclusion with Nature Medicine and recommended that a retraction was appropriate.

An early clinical study in which healthy volunteers were receiving an investigational drug targeting the same signaling pathway** was also stopped in June as a precautionary measure. This study had been intended to lay a foundation for eventual testing in MS patients but given the misrepresented data, MS is no longer a focus and no clinical studies are taking place at the moment. GSK still believes the investigational drug and the signaling pathway may have potential in other disease states.

Following the investigation GSK took appropriate action. Five R&D employees who were among the named authors of the publication have left GSK.

The company asked a retired Cambridge professor, Sir Patrick Sissons, to lead a “data review team” to review the research. It found:

  • There was no evidence that patient safety had been compromised and found no reason to suspend or stop any clinical research.

  • Data misrepresentation was found in only one publication – the retracted Nature Medicine article.

  • Two other unpublished manuscripts, involving the same small research group that drove the Nature Medicine publication, contained potentially purposeful misrepresentation of data.

  • Opportunities exist to further strengthen our existing culture and processes around data management.

  • The recommendations of the review team are being fully implemented and will be embedded as standard practice.

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7 Responses

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  1. GlaxoSmithKline is as big as the pharma giants get. The important question is how much of GSK’s data in the literature is fraudulent, or manipulated? Let’s be honest, there is every interest (and solid financial rewards) to show positive data by a pharma company in medical journals. In this case, the scientific community was lucky because an astute ANONYMOUS scientist detected the errors and reported them. But what about all other GSK data? Have researchers falsified subjects, data, or papers? Is GSK ensuring public transparency by looking into all of its published papers? The last sentence of the retraction notice is worrisome. It suggests that only about half of the authors agreed to signing the retraction note, and even so, only of an “initial version of the retraction” was agreed. So, why has the publisher and GSK not released this elusive “initial version” alongside the “final version” we can observe above? Something smells fishy here. The wording of this “initial version” should also be made public.

    JATdS

    December 5, 2013 at 2:54 pm

    • The observant reader would have noted that the fraudulent data was not GSK data, but data supposedly provided by a university collaborator.

      Big Pharma is not interested in fraudulent data: it could easily mean hundreds of millions spent on a dead end, especially when it is an early stage discovery study like this one.

      Marco

      December 6, 2013 at 1:47 am

    • The following is speculation, so you are duly warned. According to news reports earlier this year, the Chinese government and GSK are making serious efforts to clean up various problems involving charges and, apparently, counter-charges of corruption related to GSK’s Chinese operations. It’s a complex story. Both the GSK CEO and even David Cameron have been in Shanghai within the last few days, in part to deal with the problem. Aside from the usual finger-pointing and pointless flag-waving, this is obviously a good thing. It is quite possible that this retraction is a by-product of that process (which is aimed mostly at commercial, rather than scientific, misconduct). The whole thing is murky and political, but the point is that everyone now seems to have an incentive to clean house.

      Toby White

      December 6, 2013 at 9:08 am

  2. As a general remark, it is said “Nature medicine retracts…..” but the real story is that GSK conducted an investigation into this has decided to retract the paper. Nature, Science, Cell and most other heavy league journals never retract anything despite being very aware of papers, the product they sell, containing false or fabricated data. This is the problem! If you run a shop would you sell corrupted products? The sad thing is that many universities and istitutions don’t have an effective structure to vigilate and conduct investigations into allegations this is why so much garbage is still out there. So thanks to GSK, although it is clear that this was in their interest, a pharma cannot make money on false premises.

    Paul

    December 6, 2013 at 3:09 am

  3. About two months ago it was published the article “Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice” at Science Translational Medicine (IF: 10.757).
    http://stm.sciencemag.org/content/5/206/206ra138.short

    In this paper it is described the action of the compound GSK2606414 as a treatment against Prion infection. The authors indicate that this compound could be also used as a treatment against other neurodegenerative diseases with aggregates such as Alzheimer’s.

    Please watch the interview of the corresponding author at BBC:
    http://www.youtube.com/watch?v=J4O8jCj0jvQ

    At the “Competing Interests” of the paper: J.M.A. is an employee of GlaxoSmithKline with equity holdings and stock options. GlaxoSmithKline holds patents for PERK inhibitors including GSK2606414: U.S. Pat. Appl. Publ. (2012), US 20120077828 A1 PCT Int. Appl. (2011), WO 2011119663 A1.
    J.M.A (Moreno JA) is the first author of the paper.

    As indicated in the science paper, the drug targets the mechanisms described in a previous paper from the same authors: first author Moreno JA and corresponding author Mallucci GR. This paper was published in 2012 at Nature: “Sustained Translational repression by eIF2a-P mediates prion neurodegeneration”.
    http://www.nature.com/nature/journal/v485/n7399/full/nature11058.html

    At Pubpeer, the Nature paper has been very questioned:
    https://pubpeer.com/publications/22622579

    Some of the critics:

    http://i.imgur.com/v6bgjtj.png
    http://i.imgur.com/OjlLP6W.png
    http://i.imgur.com/LzMZFzC.png
    http://i.imgur.com/A2TSzZR.png

    Jennifer Lopez

    December 6, 2013 at 7:24 am


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