[Ethical aspects of clinical trials in rare diseases].

It is estimated that there are about four million people suffering from rare diseases in Germany. For roughly the last 20 years, there has been an increasing interest in therapeutic research for rare diseases. Drug research is highly regulated via numerous laws, regulations and ethical conventions that do not offer any waivers for clinical trials in rare diseases. Thus the ethical assessment of the clinical trial application for a rare disease is basically the same as for a common disease. As the ethical standards of clinical research, for example regarding informed consent, are derived from constitutional rights and have been codified in the German drug law, it is no surprise that they cannot depend on the frequency of a disease. A very important aspect of the ethical assessment is the biometric quality with regard to study design, sample size estimation and statistical analysis, as methodologically poor research with humans is per se unethical. Problems with sample size estimations and pilot studies will be addressed in more detail. Pilot studies should be avoided and sample size estimations should not assume overoptimistic effect sizes and should not increase the error probability beyond 5% two-sided.