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The correspondents’ letters relate to the second part of our publication (1), in which we investigated possible effects of financial ties of guideline authors with pharmaceutical companies—using as our example the S3 guideline on the treatment of psoriasis with efalizumab. All comments were submitted by colleagues who were directly or indirectly involved in developing this guideline.

In response to the criticism expressed by Dr Nast and Professor Rzany, we wish to point out that, according to NICE, technology appraisals (TAs) are “recommendations on the use of new and existing medicines and treatments” (http://guidance.nice.org.uk/TA); in implementing these appraisals, clinicians have to take into consideration a patient’s individual circumstances (www.nice.org.uk/nicemedia/pdf/TA104guidance.pdf). In the same way as S3 guidelines, TAs are developed following the principles of evidence based medicine (EBM). In our opinion, therefore, the guidance is comparable to an S3 guideline. The focus of our work was not the evaluation of efalizumab compared with etanercept, but the differing evaluations of efalizumab in two guidelines whose authors had financial ties to pharmaceutical manufacturers (S3) or not (NICE guidance). The members of the guideline committee at NICE did not have competing interests, but invited guests at a hearing did (www.nice.org.uk/niceMedia/pdf/TAC_110505_confirmed.pdf). We do not criticize the inclusion of experts with competing interests with regard to targeted questions. They should, however, not be included in any balloting. In our comparison we aimed to restrict ourselves to independent guidelines that provide clinical recommendations. For this reason we did not consider the guideline from the British Association of Dermatologists (whose authors have manifold competing interests), nor the Health Technology Assessment report from DIMDI (no clinical recommendations regarding efalizumab).

Our invitation to have a discussion with the authors of the S3 guideline, which we extended in 2011 after presenting some of our results at the EBM conference in Berlin, still stands, of course.

In response to Prinz and Streit: in contrast to the S3 guideline, the NICE guidance describes, in a neutral fashion, study results regarding a questionnaire that aims to collect data on quality of life in skin disorders (Dermatology Life Quality Index, DLQI), which has been subject to criticism (www.nature.com/jid/journal/v132/n1/pdf/jid2011238a.pdf). With regard to previously treated patients, the NICE guidance includes an expert opinion that relates to the patients included in the studies.

In response to Strömer and Reusch, we wish to point out that we think that an association between the publication of the guideline and the increase in the use of efalizumab is entirely within the realm of the possible. The dissertation in which the S3 guideline was evaluated under the supervision of the leading guideline authors includes a pertinent discussion. Regarding the use of efalizumab in psoriatic arthritis, a self critical comment says: “[…] in this aspect, the guideline’s recommendations will have to be made even clearer” (2).

We did not “arbitrarily” select the psoriasis guideline, as Follmann suspects. The background was the heterogeneous prescribing behavior among dermatologists with regard to efalizumab, which became obvious from cost effectiveness audits as well as from their own statements. And all this at a time when efalizumab was still on the market, and without any knowledge of the numerous industrial ties of the authors.

Follmann emphasizes—as does Kopp in her editorial (3)—that the guideline under study was published in 2006. The AMWF published its recommendations for handling conflicts of interest in April 2010. Recent studies have shown that these recommendations are still not being put into practice to a sufficiently high extent and that the handling of declared conflicts of interest is not unequivocally regulated (4, 5).

Even in the current version of the psoriasis guideline, published in 2011, the AWMF recommendations were followed to an unsatisfactory degree (www.psoriasis-leitlinie.de/uploads/pdf/Pso_LL_COI.pdf):

  • The majority of authors report numerous ties to pharmaceutical manufacturers.
  • The authors themselves confirm, however, that in their opinion, this does not result in any conflicts of interest.
  • The project manager of the guideline is an expert who declares acting as a consultant to the pharmaceutical industry.

A “critical consultancy”, such as mentioned by Kaufmann, is an illusion, in our opinion (6).

In conclusion, we wish to mention a recent publication that presents eight criteria that may serve as warning signs of biases of guideline recommendations (7). These include:

  • The sponsor is a specialty society that receives substantial financial funding from the pharmaceutical industry;
  • Several members of the guideline groups have financial conflicts of interest;
  • The guideline has not been externally validated.

We think that adhering to these criteria is important in order to avoid negative effects of financial conflicts of interest on the quality of guidelines and in order to simultaneously establish an independent guideline culture, which focuses primarily on the patients’ benefit.

DOI: 10.3238/arztebl.2014.0037b

Dr. med. Gisela Schott

Dipl.-Biol. Henry Pachl

Prof. Dr. med. Wolf-Dieter Ludwig

Arznei­mittel­kommission der deutschen Ärzteschaft, Berlin

gisela.schott@akdae.de

Claudia Dünnweber, MPH

Berlin School of Public Health, Charité, Universitätsmedizin Berlin

Prof. Dr. med. Bernd Mühlbauer

Institut für Pharmakologie, Klinikum Bremen-Mitte gGmbH

Prof. Dr. med. Wilhelm Niebling

Lehrbereich Allgemeinmedizin, Albert-Ludwigs-Universität Freiburg i. Breisgau

Prof. Dr. med. Wolf-Dieter Ludwig

Klinik für Hämatologie, Onkologie und Tumorimmunologie, HELIOS Klinikum Berlin-Buch

Conflict of interest statement

Dr. Schott is employed by Arzneimittelinformationsdienst AID e.V.

Ms. Dünnweber, M.P.H., has an employment relationship with the German Private Health Insurance Association (Verband der privaten Kran­ken­ver­siche­rung).

Mr. Pachl, Dipl.-Biol., is employed by Arzneimittelinformationsdienst AID e.V.

Prof. Mühlbauer, Prof. Niebling, and Prof. Ludwig state that they have no conflicts of interest.

1.
Schott G, Dünnweber C, Mühlbauer B, Niebling W, Pachl H, Ludwig WD: Does the pharmaceutical industry influence guidelines? Two examples from Germany. Dtsch Arztebl Int 2013; 110(35–36): 575–83. VOLLTEXT
2.
Hofelich V: Ergebnisse zur Evaluation der S3-Leitlinie zur Therapie der Psoriasis vulgaris in Deutschland: www.diss.fu-berlin.de/diss/servlets/MCRFileNodeServlet/FUDISS_derivate_000000006571/Promotion_online.pdf. Dissertation; Klinik für Dermatologie, Venerologie und Allergologie der Medizinischen Fakultät Charité – Universitätsmedizin Berlin, Januar 2010 (last accessed: 1 November 2013).
3.
Kopp I: Conflicts of interest—an ever present challenge. Dtsch Arztebl Int 2013; 110(35–36): 573–4. VOLLTEXT
4.
Langer T, Conrad S, Fishman L, et al.: Conflicts of interest among authors
of medical guidelines: an analysis of guidelines produced by german specialist societies. Dtsch Arztebl Int 2012; 109: 836–42. VOLLTEXT
5.
Schmutz S: Angaben zu Interessenkonflikten in Leitlinien der AWMF. Masterarbeit im Weiterbildenden Masterstudiengang „Master of Public Health“, Berlin School of Public Health, Charité – Universitätsmedizin Berlin, vorgelegt am 31. Mai 2013.
6.
Sismondo S, Doucet M: Publication ethics and the ghost management of medical publication. Bioethics 2010; 24: 273–83. CrossRef MEDLINE
7.
Lenzer J, Hoffman JR, Furberg CD, Ioannidis JP, Guideline Panel Review Working Group: Ensuring the integrity of clinical practice guidelines: a tool for protecting patients. BMJ 2013; 347: f5535. CrossRef MEDLINE
1.Schott G, Dünnweber C, Mühlbauer B, Niebling W, Pachl H, Ludwig WD: Does the pharmaceutical industry influence guidelines? Two examples from Germany. Dtsch Arztebl Int 2013; 110(35–36): 575–83. VOLLTEXT
2.Hofelich V: Ergebnisse zur Evaluation der S3-Leitlinie zur Therapie der Psoriasis vulgaris in Deutschland: www.diss.fu-berlin.de/diss/servlets/MCRFileNodeServlet/FUDISS_derivate_000000006571/Promotion_online.pdf. Dissertation; Klinik für Dermatologie, Venerologie und Allergologie der Medizinischen Fakultät Charité – Universitätsmedizin Berlin, Januar 2010 (last accessed: 1 November 2013).
3.Kopp I: Conflicts of interest—an ever present challenge. Dtsch Arztebl Int 2013; 110(35–36): 573–4. VOLLTEXT
4.Langer T, Conrad S, Fishman L, et al.: Conflicts of interest among authors
of medical guidelines: an analysis of guidelines produced by german specialist societies. Dtsch Arztebl Int 2012; 109: 836–42. VOLLTEXT
5.Schmutz S: Angaben zu Interessenkonflikten in Leitlinien der AWMF. Masterarbeit im Weiterbildenden Masterstudiengang „Master of Public Health“, Berlin School of Public Health, Charité – Universitätsmedizin Berlin, vorgelegt am 31. Mai 2013.
6.Sismondo S, Doucet M: Publication ethics and the ghost management of medical publication. Bioethics 2010; 24: 273–83. CrossRef MEDLINE
7.Lenzer J, Hoffman JR, Furberg CD, Ioannidis JP, Guideline Panel Review Working Group: Ensuring the integrity of clinical practice guidelines: a tool for protecting patients. BMJ 2013; 347: f5535. CrossRef MEDLINE

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