Response to allegations and some considerations on interferon treatment in Beh?et’s disease
http://www.100md.com
《英国眼科学杂志》
Hacettepe University Medical School, Department of Internal Medicine, Ankara, Turkey
Correspondence to:
H Demiroglu
Selimiye Cad, 1 Sok 5/21, Yukari Ayranci, Ankara, Turkey; halukdemiroglu@yahoo.com and halukd@hacettepe.edu.tr
Accepted for publication 13 May 2003
Keywords: Beh; et; s disease; interferon
Kotter et al refer to some problems, such as fabrication of authorship, possibly data, and ethical transgressions,1 in our article published in the Lancet.2 However, they do so without knowing the current facts about an ongoing process. They cite accusations that rely on an unfinalised investigation from the year 2000. As we are now in 2003, I do feel that I have to present updated correct information.
Before I do that, however, I would like to note that the best scientific evidence against fabrication of the results is its reproducibility by other groups. The results of Kotter et al1 show the beneficial effect of interferon in Beh?et’s disease just as our results did,2 and our results are being increasingly reproduced.
The fact that the accusations were made on the basis of an unfinalised investigation was clear in the editorial3 and letter4 written about our article at the time. The editor of the Lancet stated that "... further investigations are in progress"3 and the Dean of our medical school stated that "... the issue will be finalised ... in a court of law."4 I would like to report on the decisions made by courts of law during the 3 year period since then.
First of all, during ongoing inquires about the article,2 it was established without doubt by an investigating commission that all my coauthors had already known that their names were included as coauthors before the article was published. None of the coauthors had objected to the inclusion of his/her name at the time. It was not until 2 months after the publication that some of the coauthors claimed that they were unaware of inclusion of their names. It is noteworthy that they did so only after an ethical inquiry was embarked upon. The issue of fabricated authorship was brought to a court, accusing me of forging signatures. The court unambiguously declared my innocence at its first session on the matter on 3 April 2003, concluding that there was no forging of signatures and that it cannot be imagined that the coauthors had been unaware of the article given the totality of the circumstances surrounding the issue.5 This conclusion is supported independently.6,7 As attested by those court decisions, there is no fabrication of authorship.
I was also accused of possible fabrication of many of the patients.4 However, in a declaratory action taken by another court, it was definitely established that all 135 patients mentioned in the Lancet article2 were officially registered at the Hacettepe University Medical School.8
At the same time, the highest administrative court, the State Council of Turkey (Danistay) issued a stay order against any administrative act due to the claimed ethical transgressions,9 in favour of me. This decision was further approved at a plenary session held at the State Council of Turkey with the participation of members from all administrative chambers of the court.10
Kotter et al are unintentionally perpetuating incorrect accusations about me in the BJO.1 I am hoping the impropriety of those accusations is clear in light of all the independent court decisions I describe above. Judicial decisions should be respected by everyone who believes in upholding the supremacy of law. It is my natural right to respond and the readers of the BJO deserve to be informed by updated correct information.
There is no indication that either authorship or the results reported in the Lancet article2 were fabricated. Besides judicial decisions, the best scientific evidence that the data are not fabricated is their reproducibility by other groups, as I mentioned at the beginning. It is well shown in the literature that our results2 are being increasingly reproduced, and I am happy to see that. In our clinic, we have been using interferon in Beh?et’s disease since the early 1990s and we are among the first groups to use it in this disease. We published our preliminary results previously.11,12 The main problem in Beh?et’s disease is to prevent serious complications such as vascular thrombotic attacks, ocular involvement, and their recurrences.13 Conventional drugs and corticosteroids have very little, if any, effect on the course of such complications. The first 2 years of the disease is the most critical period and the disease generally runs a more severe course in patients in whom the disease is diagnosed at an age less than 30.14–16 I believe that as interferon use is increased, ocular complications of Beh?et’s disease will be minimised as well as extraocular manifestations. I suggest that the earlier we begin interferon, the better.
ADDENDUM
In the action of annulment, until a final decision was reached, the highest administrative court, the State Council of Turkey (Danistay) had issued a stay order against any administrative act due to the claimed ethical transgression,9,10 in favour of me, stating that "...the administrative act would result in damages which are difficult or impossible to compensate, and at the same time the act is clearly unlawful..." On 5 November 2003, the 12th Chamber of the State Council of Turkey arranged a trial (file no 2002/883), this time for a final decision. At the end of the session, the prosecutor of the State Council of Turkey read his opinion which agreed with the unlawfulness of the act and suggested cancellution of any administrative act, after which the court gave its final decision.
References
Kotter I, Zierhut M, Eckstein AK, et al. Human recombinant interferon alfa-2a for the treatment of Beh?et’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol 2003;87:423–31.
Demiroglu H, Ozcebe OI, Barista I, et al. Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Beh?et’s disease: a randomised trial. Lancet 2000;355:605–9.
Horton R. Retraction: Interferon alfa-2b...in Beh?et’s disease. Lancet 2000;356:1292.
Sayek I. Beh?et’s disease and interferon: flaws in research integrity of randomised trial. Lancet 2000;356:1351.
Turkish Republic, Ankara 3rd Court of General Criminal Jurisdiction; file no: 2003/256, decision no: 2003/335.
Turkish Republic, Ministry of Justice, General Directorate of Criminal Affairs, no: 2003/4137 .
Turkish Republic, Ankara 3rd Administrative Court; file no: 2000/1121.
Turkish Republic, Ankara 2nd Civil Court of First Instance; file no: 2002/66 different work.
12th Chamber of The State Council of Turkey; file no: 2002/883.
Plenary session, The State Council of Turkey, no: 2002/340.
Caliskan S, Eldem B, Demiroglu H, et al. Interferon alpha-2b in the treatment of ocular Beh?et’s disease. Middle East J Ophthalmol 1995;3:94–9.
Dundar S, Demiroglu H, Ozcebe O, et al. Alpha interferon in Beh?et’s disease. Hematol Rev 1996;9:285–90.
Demiroglu H, Yalcin S, Buyukasik Y, et al. Vascular thrombotic problems in Beh?et’s disease. Acta Haematol 1997;98:172.
Demiroglu H, Barista I, Dundar S. Assessing the risk of deep vein thrombosis in Beh?et’s disease. Thromb Res 1996;84:297–8.
Demiroglu H, Barista I, Dundar S. Risk factor assessment and prognosis of eye involvement in Beh?et’s disease in Turkey. Ophthalmology 1997;104:701–5.
Bardak Y. Effects of age and sex on Beh?et’s disease. J Rheumatol 1999;26:1008–9.(Haluk Demiroglu)
Correspondence to:
H Demiroglu
Selimiye Cad, 1 Sok 5/21, Yukari Ayranci, Ankara, Turkey; halukdemiroglu@yahoo.com and halukd@hacettepe.edu.tr
Accepted for publication 13 May 2003
Keywords: Beh; et; s disease; interferon
Kotter et al refer to some problems, such as fabrication of authorship, possibly data, and ethical transgressions,1 in our article published in the Lancet.2 However, they do so without knowing the current facts about an ongoing process. They cite accusations that rely on an unfinalised investigation from the year 2000. As we are now in 2003, I do feel that I have to present updated correct information.
Before I do that, however, I would like to note that the best scientific evidence against fabrication of the results is its reproducibility by other groups. The results of Kotter et al1 show the beneficial effect of interferon in Beh?et’s disease just as our results did,2 and our results are being increasingly reproduced.
The fact that the accusations were made on the basis of an unfinalised investigation was clear in the editorial3 and letter4 written about our article at the time. The editor of the Lancet stated that "... further investigations are in progress"3 and the Dean of our medical school stated that "... the issue will be finalised ... in a court of law."4 I would like to report on the decisions made by courts of law during the 3 year period since then.
First of all, during ongoing inquires about the article,2 it was established without doubt by an investigating commission that all my coauthors had already known that their names were included as coauthors before the article was published. None of the coauthors had objected to the inclusion of his/her name at the time. It was not until 2 months after the publication that some of the coauthors claimed that they were unaware of inclusion of their names. It is noteworthy that they did so only after an ethical inquiry was embarked upon. The issue of fabricated authorship was brought to a court, accusing me of forging signatures. The court unambiguously declared my innocence at its first session on the matter on 3 April 2003, concluding that there was no forging of signatures and that it cannot be imagined that the coauthors had been unaware of the article given the totality of the circumstances surrounding the issue.5 This conclusion is supported independently.6,7 As attested by those court decisions, there is no fabrication of authorship.
I was also accused of possible fabrication of many of the patients.4 However, in a declaratory action taken by another court, it was definitely established that all 135 patients mentioned in the Lancet article2 were officially registered at the Hacettepe University Medical School.8
At the same time, the highest administrative court, the State Council of Turkey (Danistay) issued a stay order against any administrative act due to the claimed ethical transgressions,9 in favour of me. This decision was further approved at a plenary session held at the State Council of Turkey with the participation of members from all administrative chambers of the court.10
Kotter et al are unintentionally perpetuating incorrect accusations about me in the BJO.1 I am hoping the impropriety of those accusations is clear in light of all the independent court decisions I describe above. Judicial decisions should be respected by everyone who believes in upholding the supremacy of law. It is my natural right to respond and the readers of the BJO deserve to be informed by updated correct information.
There is no indication that either authorship or the results reported in the Lancet article2 were fabricated. Besides judicial decisions, the best scientific evidence that the data are not fabricated is their reproducibility by other groups, as I mentioned at the beginning. It is well shown in the literature that our results2 are being increasingly reproduced, and I am happy to see that. In our clinic, we have been using interferon in Beh?et’s disease since the early 1990s and we are among the first groups to use it in this disease. We published our preliminary results previously.11,12 The main problem in Beh?et’s disease is to prevent serious complications such as vascular thrombotic attacks, ocular involvement, and their recurrences.13 Conventional drugs and corticosteroids have very little, if any, effect on the course of such complications. The first 2 years of the disease is the most critical period and the disease generally runs a more severe course in patients in whom the disease is diagnosed at an age less than 30.14–16 I believe that as interferon use is increased, ocular complications of Beh?et’s disease will be minimised as well as extraocular manifestations. I suggest that the earlier we begin interferon, the better.
ADDENDUM
In the action of annulment, until a final decision was reached, the highest administrative court, the State Council of Turkey (Danistay) had issued a stay order against any administrative act due to the claimed ethical transgression,9,10 in favour of me, stating that "...the administrative act would result in damages which are difficult or impossible to compensate, and at the same time the act is clearly unlawful..." On 5 November 2003, the 12th Chamber of the State Council of Turkey arranged a trial (file no 2002/883), this time for a final decision. At the end of the session, the prosecutor of the State Council of Turkey read his opinion which agreed with the unlawfulness of the act and suggested cancellution of any administrative act, after which the court gave its final decision.
References
Kotter I, Zierhut M, Eckstein AK, et al. Human recombinant interferon alfa-2a for the treatment of Beh?et’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol 2003;87:423–31.
Demiroglu H, Ozcebe OI, Barista I, et al. Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Beh?et’s disease: a randomised trial. Lancet 2000;355:605–9.
Horton R. Retraction: Interferon alfa-2b...in Beh?et’s disease. Lancet 2000;356:1292.
Sayek I. Beh?et’s disease and interferon: flaws in research integrity of randomised trial. Lancet 2000;356:1351.
Turkish Republic, Ankara 3rd Court of General Criminal Jurisdiction; file no: 2003/256, decision no: 2003/335.
Turkish Republic, Ministry of Justice, General Directorate of Criminal Affairs, no: 2003/4137 .
Turkish Republic, Ankara 3rd Administrative Court; file no: 2000/1121.
Turkish Republic, Ankara 2nd Civil Court of First Instance; file no: 2002/66 different work.
12th Chamber of The State Council of Turkey; file no: 2002/883.
Plenary session, The State Council of Turkey, no: 2002/340.
Caliskan S, Eldem B, Demiroglu H, et al. Interferon alpha-2b in the treatment of ocular Beh?et’s disease. Middle East J Ophthalmol 1995;3:94–9.
Dundar S, Demiroglu H, Ozcebe O, et al. Alpha interferon in Beh?et’s disease. Hematol Rev 1996;9:285–90.
Demiroglu H, Yalcin S, Buyukasik Y, et al. Vascular thrombotic problems in Beh?et’s disease. Acta Haematol 1997;98:172.
Demiroglu H, Barista I, Dundar S. Assessing the risk of deep vein thrombosis in Beh?et’s disease. Thromb Res 1996;84:297–8.
Demiroglu H, Barista I, Dundar S. Risk factor assessment and prognosis of eye involvement in Beh?et’s disease in Turkey. Ophthalmology 1997;104:701–5.
Bardak Y. Effects of age and sex on Beh?et’s disease. J Rheumatol 1999;26:1008–9.(Haluk Demiroglu)