Our qualitative systematic literature review aimed to explain the influence that financial funding from pharmaceutical companies has on different aspects during the course of a drug trial.
In spite of a comprehensive literature search in the database that is relevant for this topic (PubMed) and the reference lists of included studies, however, we can obviously not rule out that our results were influenced by search and publication bias, as Braschoß suspects.
Publication bias is a problem in many areas within medicine, and we aimed to raise awareness of this with our article. The included studies were not based only on the evaluation of publications, as Grass and Mäder write, but on the evaluation of different data, including study protocols, that had been presented to an ethics committee. Maares asks for a quantitative analysis, which we were not able to undertake in view of the wide methodological heterogeneity of the included studies.
We presented the results of our literature search in detail (see also eTables). These are not wholesale accusations, as Throm (from the Association of Research-based Pharmaceutical Companies) assumes, but a neutral presentation of the results of the included studies. The Association of Research-based Pharmaceutical Companies declares in a publication which is accessible from the organization’s homepage that publication bias is a “historical topic.” Our overview shows, however, as other current studies do, that this is unfortunately not the case (1). The most recent studies we were able to include in our overview as data sources were published at the end of 2008, several years after the voluntary commitment that the pharmaceutical industry entered into in 2005—namely, to register studies and publish results. Recent examples, such as reboxetin in the past year, have shown that non-publication of data by pharmaceutical companies is by no means a thing of the past (2).
Even now, public access to study data is not given, and the opening of the EudraCT database will change this only to a limited degree, since, for example, access to study results is currently not planned. The European Assessment Reports (EPARs) of the European Medicines Agency (EMA) contain only data that manufacturers make available for approval. Independent evaluation of drugs is not possible by using these reports. The pharmaceutical industry continually reminds us that licensing authorities require placebo-controlled studies. However, they also ask for the use of comparable active substances—for example, as listed in our article, in the context of randomized controlled studies of psoriasis (3). The argument presented by Grass and Mäder, that pharmaceutical companies are more likely to fund studies that have a high likelihood of a successful outcome, is rendered void by the fact that in direct paired comparisons of substances—for example, different antipsychotic drugs—the results went in favor of whichever pharmaceutical company was funding the study (4). The investigation of difficulties and weaknesses of non-industry funded studies was not the topic of our analysis; however, we agree with Grass and Mäder that these also entail problems that may lead to distortions.
We agree with Freund about the urgent need for more public funding for clinical drug trials. As Freund suggests, a proportion of the healthcare costs could be spent on these. In Italy, another solution has been a success (5). It was made a legal requirement for all pharmaceutical companies based in the country to pay 5% of their advertising expenditure to the Italian licensing authority, which uses this money to fund the independent clinical research that is so urgently needed in order to evaluate drugs in everyday conditions (6). In addition to funding independent clinical studies, measures need to be in place to guarantee that conducting such studies is actually feasible and doable in the context of everyday clinical practice. We therefore thank our colleagues Freund, Maier, and Zenz for mentioning the practical difficulties that have resulted from the implementation of the Clinical Trials Directive in national law by means of the 12th revision of German Drug Registration and Administration Act.
Sachtleben criticizes among other issues the dependency of academic careers from pharmaceutical companies’ third-party funding. Establishing independent research in Germany would certainly help to ameliorate this problem. For this reason, the bureaucratic hurdles for academia-initiated studies need to be dismantled and sufficient public funding needs to be made available.
Prof. Dr. med. Klaus Lieb
Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin Mainz
Prof. Dr. med. Wolf-Dieter Ludwig
Klinik für Hämatologie, Onkologie und Tumorimmunologie,
HELIOS Klinikum Berlin-Buch
Arzneimittelkommission der deutschen Ärzteschaft, Berlin
Dr. med. Gisela Schott
Arzneimittelkommission der deutschen Ärzteschaft
10623 Berlin, Germany
Conflict of Interest Statement
The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.
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|2.||Institut für Wirtschaftlichkeit und Qualität im Gesundheitswesen (IQWiG): Antidepressiva: Nutzen von Reboxetin ist nicht belegt. Pressemitteilung vom 24. November 2009.|
|3.||EMA, CHMP: Guideline on clinical investigation of medicinal products indicated for the treatment of psoriasis. London, 18. November 2004; Doc. Ref. EMEA/CHMP/EWP/2454/02. Last accessed on 30 June 2010.|
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