Clinical Research in Germany

Pivotal clinical studies almost never originate from Germany, is the way one might be tempted to describe the present status of clinical research in the third largest economy of the world. It is also appalling to see the decay of the former “pharmacy of the world” into the state of a second line country - with the certain impression of no positive development at all.

Clinical research is terribly expensive. Developmental costs of an investigational new drug (IND) may come to as much as a billion dollars, two thirds of which are spent in the clinical stages of research. It is therefore obvious that pharmaceutical companies as the major, though certainly not the only, sponsors of clinical research are important here.

At present Germany is not an attractive location for pharmaceutical companies or even for companies in general: it has extensive and expensive economic drawback in terms of taxes and social security deductions, almost unlimited employee job protection, powerful labour associations. These obstacles are only a few of those which could be named. These pitfalls deter companies from investments with Germany in general. However, scientifically active pharmaceutical companies face additional problems. Clinical research has not yet fully recovered from World War II, evidence-based medicine is certainly not a German invention. The deficits in this regard are regularly documented, with the latest criticism stemming from the the Boston Consulting Report (Boston Consulting Group [eds.], Wettbewerbsfähigkeit Deutschlands als Standort für Arzneimittelforschung und -entwicklung, November 2001, http://www.bcg.de/produktion/Reports/WebSite/pdf/1016196061320/10161960613201.pdf) which was commissioned by the German Association of Research-Based Pharmaceutical Companies (Verband der forschenden Arzneimittelhersteller VFA). It shows no significant improvement in the number of international clinical studies published from Germany compared to van Gijn's analysis in 1996 (Van Gijn J, Randomised trials. Lancet 1996; 347: 1234 - 1235). This disappointing result is a bit astonishing as there have been clear, substantial commitments of public institutions to funding in this area, especially by the German Federal Ministry of Education and Research (BMBF). There have been multimillion Deutschmark/Euro programmes to promote key positions, e.g. in clinical pharmacology, networking programmes for particular disease areas (MedNets) and clinical research centers (KKS). These positive investments were highly appreciated by the scientific community and it was hoped that a new era of clinical research was about to commence. Why did the scientific output of clinical research not measurably respond to these well-positioned funding initiatives?

The key issue - as stated above - is money, the second is reputation and legal issues are the third.

The main politically independent, public science funding organisation in Germany is the Deutsche Forschungsgemeinschaft (DFG). Its commitment to clinical research is minute so far. It has a commission for clinical research, but - in terms of visible outcome - this commission so far has only re-established clinical research groups (Klinische Forschergruppen). This funding model served quite well in the past, but could not and will not support larger clinical trials. It therefore represents an inadequate tool to cope with the deficits of clinical trials in Germany. Other potential attempts by the DFG to implement a greater commitment to clinical studies, e.g. by special expert panels or a clear partial dedication of existing funding programmes (e.g. Heisenberg scholarship), at least to date have not reached the public. There is an overwhelming impression that even the DFG's own manifest for clinical research, “Denkschrift zur Klinischen Forschung”, so far did not visibly impact on the structure of the DFG.

Apart from the acute economic disaster, one of the many reasons for this seems to be the low scientific reputation of clinical studies which is expressed by many “hardcore” in vitro researchers, including those dominating the central structures of the DFG. It is obvious that large impact factors, personal rewards and career promotions are much more attainable by in vitro than by clinical studies.

A re-evaluation of researchers' merits within the realm of clinical studies seems to be overdue, and specifics of this area have to be incorporated into a balanced judgement. The easiest way to increase the value of related papers might be the introduction of a multiplier (e.g. 2 - 4 times the actual impact factor) in the personal and institutional scoring scheme, which is increasingly used in Germany to direct state funding of universities. This is just one potential instrument, but it could reflect the tremendous attempts of the many involved in clinical studies who cannot all become first or senior authors even if a series of papers is produced.

The third problem lies in the legal framework for clinical research which in Germany is massively overregulated. Patent claims of universities put off pharmaceutical companies, multicentre studies need to pass 20 - 30 separate ethics committees (IRB). The worst, however, which can happen to a trialist is prosecution under the charge of corruption or, to use a more German term, “Vorteilsnahme” which means that the possibility might exist that professional decisions of a state employee are affected by potential advantages (e.g. money, travel or study grants). Researchers are encouraged to attract industry support on the one hand, and on the other hand are prosecuted for doing so. A clear legislative act to define conditions and rules for interactions between public institutions, including universities, and industry is urgently needed. This regulation must include a framework of monetary compensations for “after hour” clinical research which at present is severely restricted in public institutions, resulting in low motivation to conduct clinical studies. On the other hand, it should also strengthen the position of the researcher with regard to the right of publication, by declaring suppressive rights on the part of the industrial sponsor to be illegal. The present practice of publication approval by the sponsor may be abused by industry if economic reasons (e.g. negative results) seem to render publication disadvantageous.

If public institutions including law makers and funding agencies will not adequately meet the demands of clinical research and change attitudes and legal conditions, this area of research will remain as an astonishing weak point of this country; not only scientific reputation but also the quality of patient care which profits from clinical research in general are at stake. A Medical Research Council (MRC) as in the UK as an organisational “center court” would certainly help a lot.

To cope with these shortcomings, the Deutsche Diabetes Gesellschaft (DDG) has recently founded a clinical trial commission (Kommission Klinische Studien), headed by Prof. Nauck, Bad Lauterberg. All members are invited to submit study proposals. At present, the Deutsche Gesellschaft für Endokrinologie (DGE) is recruiting a network of clinical trialists through their mentor organisation to promote larger clinical trials.

Both initiatives are most welcome and should be supported, as in Germany there is a great demand for progress in the culture of clinical research in general and clinical studies in particular.

Martin Wehling, Mannheim Editor-in-Chief

Helmut Schatz, Bochum Editor-in-Chief