Journal withdraws article after complaints from drug manufacturersBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2335 (Published 11 April 2011) Cite this as: BMJ 2011;342:d2335
All rapid responses
Contrary to the impression created by the article, "Journal withdraws
article after complaints from drug manufacturers," the online article by
Elashoff et al. in Gastroenterology was not retracted or withdrawn due to
complaints from drug manufacturers. Rather, the online version was
withdrawn to allow the authors to complete their final revision of the
article prior to publication of the print version scheduled for July 2011.
Competing interests: No competing interests
An analysis of the paper "Increased Incidence of Pancreatitis and
Cancer Among Patients Given Glucagon Like Peptide-1-Based Therapy" by
Michael Elashoff, Aleksey V Matveyenko, Belinda Gier, Robert Elashoff, and
Peter C Butler, to be published in Gastroenterology. (1)
This paper uses disproportionality analysis to examine reports of
pancreatitis and pancreatic cancer or thyroid cancer to the US FDA,
concerning sitagliptine or exenatide, compared to four other drugs. The
authors found excess relative reporting of pancreatitis, thyroid or
pancreatic cancer, and all-type cancer with sitagliptine. The comparators
were rosiglitazone, nateglinide, repaglinide, and glipizide.
They first examined the reporting pattern or rate (compared to all
reports) of five controls events (back pain, urinary tract infection,
chest pain, cough and syncope), which they then used as reference to
examine a possibly increased rate of reporting of the events of interest.
They found an increased relative reporting rate of pancreatitis,
pancreatic cancer and thyroid cancer with exenatide and sitagliptine
compared with the reporting of these control events in the control
medication. This study seems to be carefully thought out and there may
indeed be increased reporting of these events. As the authors point out,
in an extensive discussion, this finding may have biological plausibility,
and might have clinical consequences considering the increased risk of
cancer in type 2 diabetic subjects.
In their discussion, the authors remain prudent on the real meaning of the
results, and the fact that this concerns spontaneous reporting of adverse
reactions, which is subject to many biases, as is also its derivative
disproportionality analysis.(2-5) They call for further analyses of this
signal in real-life epidemiological studies, in addition to clinical
trials, especially if the drugs are to be used as first-line treatment of
type-2 diabetes. Epidemiological studies effectively seem more reassuring
In this context, the title of the paper, which carries the strongest
message, is clearly misleading. This study does not show increased
incidence of cancer or pancreatitis. What the paper shows is increased
reporting of these events in patients using these drugs, not increased
incidence of pancreatitis or cancer. Whether this is related to the drugs
themselves, to the characteristics of the patients or to biases in
reporting remains to be demonstrated and verified.
The authors are correct in asking for proper epidemiological studies,
considering the possible consequences on the one hand of an increased risk
of pancreatitis and cancer, and on the other of a false alarm that might
limit the recourse to what seem to be active and effective treatments of
diabetes. Maybe with a title more representative of the actual content of
This certainly is an alert, but not yet an alarm.
1. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC.
Increased Incidence of Pancreatitis and Cancer Among Patients Given
Glucagon Like Peptide-1 Based Therapy. Gastroenterology. 2011 Feb 17.
2. Pariente A, Didailler M, Avillach P, Miremont-Salame G, Fourrier-Reglat
A, Haramburu F, et al. A potential competition bias in the detection of
safety signals from spontaneous reporting databases. Pharmacoepidemiol
Drug Saf. 2010 Sep 16.
3. Pariente A, Daveluy A, Laribiere-Benard A, Miremont-Salame G, Begaud B,
Moore N. Effect of Date of Drug Marketing on Disproportionality Measures
in Pharmacovigilance: The Example of Suicide with SSRIs Using Data From
the UK MHRA. Drug Saf. 2009;32(5):441-7.
4. Pariente A, Gregoire F, Fourrier-Reglat A, Haramburu F, Moore N. Impact
of safety alerts on measures of disproportionality in spontaneous
reporting databases : the notoriety bias. Drug Saf. 2007;30(10):891-8.
5. Moore N, Hall G, Sturkenboom M, Mann R, Lagnaoui R, Begaud B. Biases
affecting the proportional reporting ratio (PRR) in spontaneous reports
pharmacovigilance databases: the example of sertindole. Pharmacoepidemiol
Drug Saf. 2003 Jun;12(4):271-81.
6. Dore DD, Bloomgren GL, Wenten M, Hoffman C, Clifford CR, Quinn SG, et
al. A cohort study of acute pancreatitis in relation to exenatide use.
Diabetes Obes Metab. 2011 Feb 14.
7. Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes
treated with exenatide or sitagliptin: a retrospective observational
pharmacy claims analysis. Diabetes Care. 2010 Nov;33(11):2349-54.
Competing interests: No sure, but a friend working with Lilly did ask me what I thought of the paper, and here is what I answered (with some typos corrected)
"Distaval went on sale in Britain on April 14, 1958. (Later
thalidomide was also marketed under the names Asmaval, Tensival, Valgis,
and Valgraine). It was advertised as "completely safe" and an answer to
the "mounting toll of deaths due to barbiturate poisoning."
Nigel Hawkes' timely article 'struck a chord' with me as I'm
currently in the middle of reading "The Story of Thalidomide",  from
which the above quote is taken.
As an over-the-counter sedative, the drug had first gone on sale in
Germany under the brand name, 'Contergan', marketed by Chemie Grunenthal
of Stolberg-am-Rhein. The later British licensee was Distillers Company
(Biochemical) Ltd (DCBL).
With very little background investigation, thalidomide was promoted
to the public, far and wide, as a 'wonder drug', all the time "stressing
that the drug was completely non-poisonous ... safe ... astonishingly safe
... non-toxic ... fully harmless and even that it could be taken "in
higher dosages than recommended without any danger."
By December 1959 thalidomide was well on the way to capturing the
German market and was making Grunenthal a lot of money. And that year too,
complaints from the German medical profession - particularly with regards
to the problem of peripheral neuritis - were growing ... but were busily
being suppressed by the drug makers and their representatives. Those
doctors who questioned the company's attitude were abused as troublemakers
and one doctor who told Grunenthal that it was "irresponsible" not to have
withdrawn the drug, and that he doubted the company's "trustworthiness",
was labelled 'trouble-maker No. 1'. The local German company
representative subsequently wrote to headquarters saying, "We have to pull
out this sick tooth before the infection spreads". The rest is history ...
I think it was Mark Twain who said, "History doesn't repeat itself,
but it rhymes."
 Suffer the Children: the Story of Thalidomide by the Sunday Times
Insight Team, Phillip Knightley, Elaine Potter, Harold Evans and Marjorie
Wallace: first published 1979 by Andre Deutsch, London.
Competing interests: No competing interests
Re: "Journal withdraws article after complaints from drug manufacturers", Hawkes, BMJ2011;342:dd2335
I would like to share some information for your consideration in
reference to the BMJ news article titled "Journal withdraws article after
complaints from drug manufacturers" posted online April 11, 2011, which
refers to a draft "article in press" recently withdrawn from the
Merck/MSD encourages and supports scientific discussion and debate
that contributes to the ongoing care of patients with type 2 diabetes, and
we fully support the peer review process. We submitted a letter to the
editor of Gastroenterology to express concerns about the scientific
methodology used in the exploratory analysis presented in the draft
article. The letter was submitted to the editor for consideration and did
not contain any statement regarding whether the journal should or should
not publish the article.
The BMJ news article describes concerns raised by scientists at two
pharmaceutical companies regarding the methodology used to develop the
exploratory analyses in the Gastroenterology draft article. However, it
would likely be of interest to readers to know that the European
Association for the Study of Diabetes independently posted a statement on
their website also raising scientific concerns about the Gastroenterology
draft article on March 16, 2011. The statement can be found at:
The BMJ news article also references information posted online on
March 4, 2011 by the German Diabetes Society in reference to the draft
"article in press" on the Gastroenterology website. Please note that the
German Diabetes Society updated their statement on March 7, 2011, with
additional guidance for physicians and patients. The update statement can
be found at: http://www.deutsche-diabetes-
The BMJ article notes that Novo Nordisk manufactures 'Byetta', which
is not correct. 'Byetta' is manufactured by Amylin and Lilly.
Thank you for your consideration.
Barry J. Goldstein, MD, PhD
Vice President of Clinical Research, Diabetes and Endocrinology,
Merck Research Laboratories
Competing interests: Dr Barry J. Golstein is an employee of Merck Research Laboratories