Tuesday, October 23, 2007

AIIMS researchers publish the same work in two journals


Here's the Hindustan Times report [Hat tip to Anon's comment]:

Six professors as well as the director of the All India Institute of Medical Sciences, P Venugopal, have been accused of fraudulently publishing the same research material in two different medical journals.

The article — Use of stem cells in congenital anomalies — appeared in the October-December issue of Indian Journal of Pediatric Surgeons and the January 2007 issue of International Journal Transplantation Proceedings.

The article was written by Dr D.K. Gupta, head of paediatric surgery in AIIMS. It was co-authored by Venugopal, Shilpa Sharma, Lalit Kumar, S. Dattagupta, N.K. Arora and Dr S. Mohanty. All are senior professors in the premier medical college and hospital.

Experts said this is a case of duplicate publication, considered an academic fraud. “My personal opinion is that they are based on the same data and come to very similar conclusions. Much of the text is repeated and neither paper cites the other,” said Harvey Marcovitch, chairman of the Committee on Publication Ethics (COPE), an organisation for editors of peer-reviewed journals formed to tackle breach in research and publication ethics. [Bold emphasis added]

10 Comments:

  1. Rahul said...

    Any links to the blog where this was supposedly discussed earlier? I couldn't find it.

    It would be interesting, again, to know who the corresponding authors are. And, as the article points out, why didn't Gupta contact the journals when he knew?

  2. Anant said...

    If Directors of Institutes start saying in public fora that faculty members should double their publications, then such occurencences will be more frequent?!

  3. Abi said...

    Rahul: As soon as I read that HT piece, I too looked for the blog mentioned in it. I couldn't find anything.

    I agree with you that Gupta would be on firmer ground if he had taken some corrective action earlier; his excuses do sound pretty lame.

    Anant: Shhhhh!

  4. Anonymous said...

    Hope you are well. I read, with great interest, the abstract that you sent to me. This paper describes about the usefulness of stem cells in treating meningomyelocoel in humans.
    I would like to read the complete full paper for more valid criticism as it is difficult to assess the paper from a short abstract.

    However, certain technical aspects can be commented without the fear
    of misunderstanding the paper. I suppose that this paper is from some Chinese group. Because, the director of my center Dr. Wise Young (from New York University) is gearing up in establishing a Spinal Cord Injury network in china aiming such transplants.

    My concerns are:

    (1) SOURCE OF STEM CELL:
    It has been given that autologous stem cells were used without
    mention from which site they have obtained them. Presumably, it might be from bone marrow (by iliac crest / tibial aspiration?). There was no mention about how they processed the cells and what markers they used to confirm them as stem cells.

    When bone marrow is aspirated, the resultant fluid contains not only
    stem cells but also host's blood cells in various stages of their
    maturation. Even in the stem cell population some are hemopoietic
    stem cells i.e. committed to give blood related cells and very few
    are real stem cells capable of giving rise to other types of tissues.

    The normal procedure adapted to separate such cells is to grow the
    bone marrow cells in culture for several days (i.e. several passages �

    if I am not wrong I think a minimum of 5 to 8 passage would be
    required and it will take about 3 to 5 weeks time). During that
    culture, mature blood cells will float as blood cells are not
    anchorage dependent cells. Similarly hemopoietic stem cells have senescence beyond certain divisions - they eventually die. These dead cells will also be floating. During medium changes, these floating cells (dead and matured blood cells) will be eliminated leaving behind only attached cells. Thus slowly all the cells with a definitive life (senescence) will be eliminated leaving behind the stem cell population. These stem cells are called as mesenchymal stem
    cells in contrast to embryonic stem cells. Only embryonic stem cells are capable of differentiating into any tissue based on their tissue environment. Normally, mesenchymal stem cells are known to give rise to only mesenchymal derivatives such a muscle cells and bone cells
    and it would be required to stimulate them with chemical means. For e.g. bone marrow derived stem cells can be stimulated to form neuronal line of cells by using a chemical called "beta-
    ercaptoethanol" in culture. I wonder how the authors used such
    chemicals in human babies and I doubt that such chemicals are ever
    approved for human usage. If the authors claim that they have used
    mesenchymal stem cells without such chemical stimulants, I would
    again wonder how such cells differentiated into neurons in vivo. It is unlikely that the authors have used embryonic stem cells as the procedure of collecting and processing is extraordinarily cumbersome.
    It also involves ethical issues.

    A recent report states that even such chemically induced mesenchymal stem cells (bone marrow cells) failed to form functional neurons although their morphology and neuronal markers such nestin and vimentin and mRNA expressions suggesting neuronal characteristics.
    (Choi et al Biochem Biophys Res Comm 2006) Therefore, they may
    form "neuron-like" cells but not "neurons". Thus, even the usefulness
    of transplanting "true bone marrow derived" stem cells was questioned. Under these circumstances, if the authors have used simple bone marrow aspirates, probably they have transplanted only blood cells which at the best may differentiate into nflammatory
    cells such as monocytes->macrophages and neutrophils which are not known to produce any beneficial effect in CNS transplantations.


    (2) SAFETY OF STEM CELLS FOR HUMAN USAGE
    But the major problem with stem cells is that even after long term, they continue to divide in the transplanted site. This is especially more when they are transplanted in an injured spinal cord. That means they became tumerogenic. Recently, last month, an article has been published in Science questioning the safety of stem cell transplantation in spinal cord injury as they might turn-out in neuroma or gliomas since there is no control over these cells'
    division and maturation phases.

    One approach now being thought off is to pre-differentiate those stem
    cells in vitro upto certain point (i.e. either making them neural
    restricted precursor cells or glial restricted precursor cells) and then transplant them rather than transplanting as "embryonic stem cells". But that approach kills the very purpose of doing stem cell transplant because we are not allowing the transplanted cells to produce suitable cells as required by the host tissue environment.

    My boss here is trying to prevent this tumerogenicty of embryonic
    stem cells by incorporating a gene called "Notch". In fact Notch is a
    double edged gene since it behaves like an oncogene in some cells
    (like skin cells) but act as a tumor suppressor in neurons. In fact,last week I have transplanted the notch infected embryonic stem cells in two rats as a surveillance study. But again the problem here is the Notch infection of the cells was not very effective. I.e. only
    less than 15% of the cells are getting the Notch and it means still there a bunch of cells which can be tumerogenic. My lab people here are trying to get a higher success rate in notch infection of cells.
    Also they are planning to selectively isolate the successfully notch
    infected cells from others using a flow cytometry and then transplant
    them in the spinal cord so that we can get rid off the cells without
    Notch gene. We are waiting for the results from these two animals.


    (3) SITE OF INJECTION AND MODE OF INJECTION:
    Where they have injected the stem cells? How they have injected?
    Because, I suppose, in meningomyelocoel, the deficit would be to a large extend and if they adopted multiple site direct injection, probably they will do more harm as the needle (?!) would injure some of the spared axons. I strongly believe meningomyelocoel is not a right candidate to try direct intraparenchymal neural
    transplantation. Rather, intravenous mode of injecting stem cells may be a right choice as it has been proved that such intravenously injected stem cells home to demyelinated areas selectively (Pluchino et al. 2003, Bakshi et al 2004, Imitola et al 2004) In fact, here I am going to try intravenous mode of stem cell transplantation in rats
    for contusion spinal cord injury to see their ability to home and
    reverse lesion effects.


    (4) ASSESSMENT METHODS
    I have no idea about the muscle power testing in human babies. You
    must be having a good knowledge about it. Similarly bladder and bowel control ability, I wonder how they could assess them � in what parameters? Especially when except one patient, all the remaining 14 were in the age groups of less than a year, what they mean by "improvement in bladder/bowel continence". Even if they claim some bladder/bowel continence by some means, I think, it may be due to the advancement in the age and due to spontaneous recovery chances or attributable to the simultaneous surgery they performed to all the neonates. I think you may be able to better judge this aspect.

    (5) MISSING "CONCLUSIVE PROOF"
    After transplanting stem cells if one has to claim functional
    recovery they should prove that the transplanted cells transformed
    into neurons and such neo-neurons establish synaptic connections with the existing host neurons. Of course, in human subjects / clinical trials it would not be possible to do histology but invariably histological proof would be necessary to say that transplanted cells were really integrated in the spinal cord or involved in myelination by the usage of appropriate cell markers. It is therefore all the more important to study the problem in animals and establish unambiguous proof of its effectiveness before embarking upon human trials. I am shocked to note that the authors have straight tried it in human babies without any valid animal experimentation. I am not aware of any animal studies in the area of "stem cells in MMC". The
    authors cannot quote stem cell studies in traumatic paraplegia models as the base of their human experimentation. In trauma models the neurons are normal until injury and when injured they secrete different chemical signaling agents. This cannot hold true for a congenital dysplastic neuron as it is in meningomyelocoel.

    MY FINAL IMPRESSION

    I strongly feel that this paper is without any scientific rationale.
    For an unconfirmed hypothesis and by adopting very crude methods, I
    am afraid that the authors have done great injustice to the poor
    patients (babies) as

    1. They subjected them to unnecessary transplant procedure thus exposing them to unnecessary and unknown risks of it



    2. They have given a false hope to parents as if they are going
    to do something novel to their babies to help them Recently, I saw a documentary from BBC completely exposing the cruel
    and gruesome other side of so called "clinical trials". They have showed how a anti-cancer drug prepared by Johnson and Johnson have been tested in Indian patients (in Delhi and Thirvanandhapuram) with
    out concerns about first testing them in animals and how those
    patients were cheated without mentioning them the possible side
    effects. BBC strongly criticized about the "informed consent"
    procedure as in that study the consents were obtained in English when most if not all the patients of that clinical trial were illiterates who can not understand English. BBC said that the patients of India simply sign any consent forms when presented by a doctor mainly because


    1. They think they will get free medical treatment if they say
    yes to clinical trials

    2. They strongly believe that doctor is doing / trying to do good to them.


    In that circumstances, I think, just to boast themselves as if they have done something novel research, these authors have put their patients into unnecessary risk when the benefits are not clearly established by prior animal experimentations. I think animals in India are now having better life than humans - for such experiments cannot be conducted in animals without the approval of CPCEA group.

  5. Anonymous said...

    Dear Dr ABC,



    It is true that we do really only discuss cases in our forum or council of COPE members (you might consider to sign your journal up as a COPE member), I have, however, looked at and compared the two papers you have sent along and will give you some advice.



    First, comparing the two papers it appears that this is a clear case of duplicate publication. The only parts that are substantially different are the discussion sections. And although there are some discrepancies in the numbers (27 vs 29 in the later published paper, the numbers, in fact don't quite up in that paper), the times of enrolment are the same and in many parts the text is word for word the same.



    So, as a first step you need to seek explanations from all authors. The journal editor of the second journal needs to be informed and that journal should retract the paper. You probably need to then discuss any further steps you want to take with your Board colleagues.



    I will attach the COPE flowcharts (the relevant one for you is on page 2) which will take you through how to deal with such a case of duplicate publication.

    But, I do appreciate that you are in a difficult position with the Editor of your journal being implicated.



    Please let me know if you need anything further from me at this stage and keep me informed what is happening with this case.



    I hope this is helpful

    Best wishes



    Sabine Kleinert

    Dr med Sabine Kleinert, MRCP

    VICE-Chair of the Committee on Publication Ethics

    and

    Senior Executive Editor

    The Lancet

    32 Jamestown Road

    London NW1 7BY, UK

    ph: +44 207 424 4933

    fax: +44 207 424 4911





    h.marcovitch@btinternet.com





    27.9.2007

    Dear Professor XYZ,

    Dr Godlee passed on to me your email about the Gupta papers. I apologise for the delay in responding but I was on holiday.

    The council of Committee for Publication Ethics (COPE) (www.publicationethics.uk.org) does not meet again until December so I have not had the opportunity of presenting the case at a formal meeting although I will be happy to do so if you wish.

    I have read the two papers to which you allude. My personal opinion is that they are based upon the same data and come to very similar conclusions (albeit that there are 2 extra patients in the second published version). Much of the text is repeated and neither paper cites the other.

    ICMJE guidelines, as endorsed by COPE, recommend that previous submissions or publications which pose a risk of duplication or redundancy must be declared in advance so that editors can decide how to handle the paper.

    COPE guidelines in the circumstances you detail, advise that the editor of the journal publishing the paper second should be alerted to the matter and asked to investigate. His or her first recourse should be to seek clarification from the corresponding author and, if this is unsatisfactory, the editor will need to decide whether to refer the matter for formal investigation to the authors� institution(s) as possible publication misconduct. Depending on the strength of the evidence, the editor may decide, in advance of or following that investigation, to issue a notice of duplicate publication or retraction � preferably but not necessarily with the authors� consent.

    Of course, there may be an issue regarding which journal first received the paper but that is a matter for the editor of the second journal to elucidate.

    I hope this is helpful. I reiterate this is a personal view based on my experience as chairman of COPE. It may be that COPE council, if requested to look at the matter, might make some amendment.

    Harvey Marcovitch FRCP Hon FRCPCH

    Chairman, Committee on Publication Ethics

  6. Anonymous said...

    Larger issue is that authors have put their patients ( small babies ) into unnecessary risk when the benefits are not clearly established by prior animal experimentations. The authors subjected babies to unnecessary transplant procedure thus exposing them to unnecessary and unknown risks of it. The authors have given a false hope to parents as if they are going to do something novel to their babies to help them.

  7. Anonymous said...

    At AIIMS research is not just a routine activity but rather a mission with three objectives. As anywhere else, the primary purpose of research is to gratify curiosity by disciplined activity, thereby leading to creation of new knowledge. But at AIIMS, we are also conscious of the role research can play in improving the quality of teaching. A teacher engaged in research is up to date with recent information, and can also inculcate a sprit of enquiry and freedom of thought into his/her students. Finally, research at AIIMS is apart of our national endeavour to cultivate a scientific temper and to eliminate from our society the way of authority and superstition.

    source : www.aiims.edu


    6 Six professors ....... hello ... listening ...

  8. Anonymous said...

    Changing definition of AIIMS

    All Indian Institute of Medical Sciences ......

    Than after duet of Director and Minister it was known as

    All India Institute of Political Sciences

    Yesterday some young JR in OT was calling it

    All India Institute of Plagiarism Sciences

    & still our health minister advise us not to leave INDIA
    ....

  9. Rahul said...

    Abi - your blog is becoming a leak magnet (if that isn't too mixed a metaphor).

    This is not the first time I am hearing concerns about AIIMS stem cell research.

  10. Anonymous said...

    A pediatric surgeon of AIIMS went for his tooth surgery in near by Safdarjung Hospital , Surprised Doc asked we all know that AIIMS is no.1 still you come for such a patty thing here WHY ? Our Pediatric Surgeon said .... well .... you know .... actually .... the thing is .... We are not allowed to open our Mouth in AIIMS ....