Declaration and Handling of Conflicts of Interest in Guidelines: A Study of S1 Guidelines From German Specialist Societies From 2010-2013.

BACKGROUND: Authors' conflicts of interest may affect the content of medical guidelines. In April 2010, the Association of Scientific Medical Societies in Germany (AWMF) issued recommendations on how such conflicts of interest should be dealt with. Most AWMF guidelines are so-called S1 guidelines developed by informal consensus in a group of experts. We now present the first study to date on the management of conflicts of interest in S1 guidelines. METHODS: On 2 December 2013, we selected the guidelines that had appeared from 1 November 2010 to 1 November 2013 among the 449 current S1 guidelines on the AWMF website. We extracted information about conflicts of interest from the guideline texts, reports, and/or conflict of interest statements and evaluated this information descriptively. RESULTS: There were 234 S1 guidelines in this category, developed by a total of 2190 experts. For 7% (16/234) of the guidelines and 16% (354/2190) of the experts, no individual conflict of interest statement could be found. Where conflict of interest statements were available, conflicts of interest were often declared--in 98% (213/218) of the guidelines and by 85% (1565/1836) of the authors. The most common type of conflict of interest was membership in a specialist society or professional association (1571/1836, 86%). Half of the experts acknowledged a financial conflict of interest (911/1836, 50%). Conflicts of interest were more common among experts contributing to guidelines that mainly concerned treatment with drugs or other medical products than in guidelines that did not have an emphasis of this type (397/663, or 60%, versus 528/1173, or 45%). The conflicts of interest were assessed in 11% (25/234) of the guidelines, with practical consequences in a single case. CONCLUSION: Conflicts of interest are often declared in the S1 guidelines of the AWMF, but they are only rarely assessed by external evaluators. Clear rules should be issued for how experts' declared conflicts of interest should be acted upon, whether they are of a financial nature or not.

Does the pharmaceutical industry influence guidelines?: two examples from Germany.

BACKGROUND: The recommendations in clinical guidelines are based on clinical trial findings and expert opinion. The influence of drug companies on these two factors is illustrated with two examples. METHODS: A judicially ordered expert review revealed that the market authorization holder (MAH) of gabapentin manipulated study data. Gabapentin was, therefore, chosen as an example for this article to analyze whether manipulated data serve as a basis for recommendations in German clinical guidelines. A search was carried out for manipulated publications on gabapentin that found their way into guidelines published by the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). To analyze the possible effects of financial ties between guideline authors and drug companies, the S3 guideline on the treatment of psoriasis vulgaris with efalizumab was compared with guidelines whose authors had no conflicts of interest. One of the authors of this article had noted variable prescribing practices for psoriasis among dermatologists while carrying out an economic assessment for a German state Association of Statutory Health Insurance Physicians. RESULTS: The data that had been manipulated by the MAH of gabapentin served as a basis for recommendations to prescribe gabapentin in guidelines that were published by the AWMF. Efalizumab was judged more favorably in the S3 guideline than in a guideline issued by the National Institute of Health and Care Excellence: for example, the evidence for it was judged as good, the use of efalizumab for induction and combination therapy in psoriasis vulgaris was recommended, and efalizumab was said to improve patients' health-related quality of life. CONCLUSION: Public access to all trial data must be ensured so that independent evaluations are possible. We take the view that the responsibility for creating guidelines should be borne by authors and organizations that do not have any conflicts of interest.

[Clinical trials in oncology: deficits and proposals for solution]. / Klinische studien in der onkologie - defizite und lösungsvorschläge.

Various investigations have identified deficits in clinical studies conducted for the market authorisation of haematological and oncological drugs. Based on data from European Public Assessment Reports (EPAR) of the European Medicines Agency (EMA), an analysis of the quality of these studies, which serve as the basis of marketing authorisation of currently approved drugs, is showing improvement. For example, endpoints recommended by the EMA are frequently used. However, deficits of marketing authorisation studies are still noticeable, e. g., results based on unplanned interim analyses or post hoc subgroup analyses. In addition to the improved quality of studies prior to marketing authorisation, independent clinical studies need to be conducted after marketing authorisation has been obtained, a good example of which are therapy optimisation studies (TOS) in acute lymphatic leukaemia (ALL). A goal of TOS is the examination of multimodal therapy concepts in the real world context of routine clinical practice. They can supply valuable data for drug safety and long-term observation. In order to conduct post-marketing authorisation studies, funding is required and bureaucratic hurdles associated with the 12(th) amendment to the Pharmaceutical Act will have to be reduced. The results of these studies are needed to efficiently handle limited health resources and to adequately inform and treat patients.

[The relation between publication bias and clinical trials funding]. / Publikationsbias in Abhängigkeit von der Art der Finanzierung bei klinischen Studien.

Publication bias describes the distortion of data in scientific journals resulting from the fact that studies with significant and positive results are more likely to be published than studies with negative or insignificant results. In studies funded by pharmaceutical companies publication bias has a considerable impact. It has been shown that more than half of the studies that are conducted as part of the drug approval process will remain unpublished. In addition, multiple publications of the same results, the selective use of data and the withholding of data relating to adverse drug reactions were also demonstrated. It is unclear, however, whether the probability of publication of studies funded by pharmaceutical companies is different from those not funded by pharmaceutical companies. Also, data vary as to the correlation between the type of funding of clinical studies and the length of time to publication. For the benefit of patients, everyone involved in clinical studies ought to take responsibility and facilitate access to all data.

The financing of drug trials by pharmaceutical companies and its consequences: part 2: a qualitative, systematic review of the literature on possible influences on authorship, access to trial data, and trial registration and publication.

BACKGROUND: In recent years, a number of studies have shown that clinical drug trials financed by pharmaceutical companies yield favorable results for company products more often than independent trials do. Moreover, pharmaceutical companies have been found to influence drug trials in various ways. This overview of current, systematic studies on this topic is intended to identify and characterize the particular aspects of the performance of a drug trial that can be affected by financial support from a pharmaceutical company. METHODS: Publications retrieved from a systematic Medline search on this topic from 1 November 2002 to 16 December 2009 were independently evaluated and selected by two of the authors. These publications were supplemented by further ones found in their references sections. RESULTS: 57 publications were included for evaluation in Parts 1 and 2 of this article. A number of studies revealed that many trials financed by pharmaceutical companies-in some cases, as many as half of all such trials-are never published. Moreover, multiple publications of the same findings were found, and some reports were found to include selectively published data. Further studies revealed evidence of other problems including incomplete trial registration, constraints on publishing rights, withheld knowledge of adverse drug reactions, and the use of ghostwriters who were supplied by the pharmaceutical companies. CONCLUSION: Financial support from a pharmaceutical company influences multiple aspects of the performance of drug trials and often leads to a favorable result for the corporate sponsor of the trial. Public access to trial protocols and results must be ensured. Moreover, more effort should be made to carry out drug trials independently, without the financial support of pharmaceutical companies.

The financing of drug trials by pharmaceutical companies and its consequences. Part 1: a qualitative, systematic review of the literature on possible influences on the findings, protocols, and quality of drug trials.

BACKGROUND: In recent years, a number of studies have shown that clinical drug trials financed by pharmaceutical companies yield favorable results for company products more often than independent trials do. Moreover, pharmaceutical companies have been found to influence drug trials in various ways. This paper provides an overview of the findings of current, systematic studies on this topic. METHODS: Publications retrieved from a systematic Medline search on this topic from 1 November 2002 to 16 December 2009 were independently evaluated and selected by two of the authors. These publications were supplemented by further ones found in their references sections. RESULTS: 57 publications were included for evaluation in Parts 1 and 2 of this article. Published drug trials that were financed by pharmaceutical companies, or whose authors declared a financial conflict of interest, were found to yield favorable results for the drug manufacturer more frequently than independently financed trials whose authors had no such conflicts. The results were also interpreted favorably more often than in independently financed trials. Furthermore, there was evidence that pharmaceutical companies influenced study protocols in a way that was favorable to themselves. The methodological quality of trials financed by pharmaceutical companies was not found to be any worse than that of trials financed in other ways. CONCLUSION: Published drug trials that are financed by pharmaceutical companies may present a distorted picture. This cannot be explained by any difference in methodological quality between such trials and trials financed in other ways.