Key points are not available for this paper at this time.
Problems of statistical and conceptual design of experiments are exacerberated by ethical issues in many, if not most, clinical trials. Statutory requirements of demonstrated effectiveness are far from being clearly resolved--either qualitatively or quantitatively. Ethics, bolstered by informed consent, are likely to keep us from ever learning the answer to many questions. Unbalanced boundaries, focusing-down designs, historical controls, and not-very-sequential designs are among the possible consequences.
John W. Tukey (Fri,) studied this question.