Clinical evaluative research: Which patients benefit, how and when? A contribution to a european discussion

Abstract

Clinical medicine is a pragmatic science, quite different from "arts" or "applied" sciences. One of its central characteristics is the continuous scientific evaluation of actual consequences of clinical judgements, decisions, and actions. This is achieved mainly by clinical-evaluative patient-centred research with its most powerful tool, the randomised controlled trial (RCT). Its results are the main substrate of evidence-based clinical prevention, diagnosis, prognosis, therapy and rehabilitation. These interventional (and artificial) trials establishing "efficacy" have to be supplemented by noninterventional ("effectiveness") studies such as outcome observations, register studies, and post marketing studies. Recently the European Parliament and the Council issued a Directive "on the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use" (200 1/20/EG). It has to be adopted and transformed into national law of the member states at the latest by the 1st of May 2004. Article 3 section 2 (a) states: "A clinical trial may be undertaken only if, in particular: the foreseeable risks and inconveniences have been weighed against the anticipated benefit for the individual trial subject and other present or future patients! Minors and incapacitated adults "should (normally) be included in clinical trials only when there are grounds for expecting that the administering of the medicinal product would be of direct benefit to the patient, thereby outweighing the risks" (Consideration 3). Later article 4 permits clinical trials on minors but not incapacitated adults which provide "some direct benefit for the group of patients" to which the study subject belongs. However, Article 2 Definitions do not provide any definition of "benefit" and "direct benefit Similar statements can be found in the World Medical Association Declaration of Helsinki (2002; No. 16), the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine issued by the Council of Europe in April 1997 (Article 16 (ii)) and its Draft Additional Protocol on Biomedical Research (Article 6 (1)). Trials, on the other hand, have to produce "credible" results, should have "relevance" and scientific merit, and must not include "obsolete or repetitive tests Thus the directive seems to require two discrete qualities: scientific originality and validity and a positive balance between the trial subjects benefits and risks. In the following, these two qualities are studied more closely with a main focus on the potential of trials to directly benefit their participants. © 2005 Springer-Verlag Berlin Heidelberg.