Ethical Considerations in Clinical Trials

Accessible online at: www.karger.com/journals/hed Ethical aspects of biomedical research in humans have been unmasked at a late stage in the history of science. They have been apparent for not more than approximately 60 years, and did not gain attention as a result of ongoing refinements of fundamental human rights. On the contrary, their recognition followed a traditional pattern in the history of human rights, in which the occurrence of severe, mass-scale atrocities is the tragic eye-opener, starting a global rebound reaction that leads to measures for regulation, control, education and prevention [1]. Now, after half a century’s development, one can speak of not only a reaction, but a strong worldwide movement that has made ethics an obligatory component of scientists’, editors’, universities’ and ministries’ responsibility for the quality of research projects far beyond their technical qualities. However, the ethical demands in research have not only expanded over the world. An extension has also been seen in a temporal perspective for individual projects involving humans. Consequently, a research protocol today will not only include ethical considerations before the start of a project, but also during and after, and not only related to the research subjects but also to the researcher’s reliability, i.e. his or her personal ethics. Before initiating a project, the ethical control comprises assuring the project’s accordance with international guidelines or conventions [1, 2] and with the home country’s legislation, if the national development has led to such judicial regulation [3]. But irrespective of differences between national control structures, a given biomedical project involving humans will have to pass at least one so-called research ethical committee (sometimes internationally grouped as institutional review boards, an outdated general term, because now the most developed systems do not rely on institutional committees, but are built up of more independent committees with a much broader base than an institution). A good starting point for clinical researchers is consequently to anticipate the analytic steps that most developed committee systems take today, even more and more generalized through, for instance, the Council of Europe’s work via its Bioconvention [2] and the derived Protocol expected to be published in 2000 [4]. The first step is to evaluate the originality of a project’s underlying idea. If it is very trivial, i.e. unlikely to generate any new knowledge, it might even fall at this stage, based on the saying that ‘every project involving man and not fulfilling the simplest scientific demands is in itself unethical, even if nonrisky’. Purely ‘me too’ trials represent such projects, with the only exception that an identical trial, number two or three after the original one, might be valuable in order to minimize the influence of statistical type one and type two errors. Still another technical hurdle has to be overcome before the ethical analysis starts: the methodology chosen in order to procure a potential answer to the initial question. If the methods, the variables, the patient numbers, the bias control, the randomization and other key aspects are obviously invalid, the project will not proceed to the committee’s next analytic step, even if the idea was original. Sometimes committees will try to help young scien-