Several years ago, the University of Minnesota hosted a lecture by Alan Milstein, a Philadelphia attorney specializing in clinical trial litigation. Milstein, who does not mince words, insisted on calling research studies “experiments.” “Don't call it a study,” Milstein said. “Don't call it a clinical trial. Call it what it is. It's an experiment.” Milstein's comments made me wonder: when was the last time I heard an ongoing research study described as a “human experiment”? The phrase is now almost always (...) associated with abuses. Asking a prospective subject to sign up for a medical experiment would probably get roughly the same response as asking him or her to sign up for a police interrogation. It wasn't always this way. In the early days of American bioethics, scholars used the word “experimentation” in the same neutral way that they later began to use “research study” and “clinical trial.”. (shrink)

Procedures for the selection of subjects for participation in randomized clinical trials--usually formalized as eligibility criteria in the study protocol--have both scientific and ethical implications. In this thesis, I undertake an examination of eligibility criteria at three stages in the genesis and dissemination of medical knowledge: clinical trial protocol, interpretation by investigators, and reporting of study results.In the first chapter, ethical issues in subject selection are reviewed and the main study questions are presented. In the second chapter, the results of (...) an examination of eligibility criteria in two sets of clinical trials, one sponsored by the NSABP, the other sponsored by POG, covering a twenty-year time span are presented. The POG trials had far fewer eligibility criteria than the NSABP studies, suggesting that large numbers of criteria may not be necessary for high quality research. In the third chapter, the impact of subjective eligibility criteria on enrollment and investigator uncertainty is explored. Subjective criteria were associated with more variable enrollment decisions and greater uncertainty. Such criteria represent a threat to the validity, conduct and interpretation of trials and, therefore, should only be included when carefully justified. The fourth chapter examines the accuracy of the reporting of eligibility criteria in sets of corresponding study protocol, methods paper, journal article, and Clinical Alert. Important information is lost at each step in the dissemination of study results. Unnecessary criteria ought to be dropped at a trial's inception; all other criteria must be reported faithfully. The fifth chapter attempts to provide a comprehensive philosophical account of just selection procedures for clinical research using the political philosophy of Michael Walzer. The sixth, and last, chapter, discusses explanatory and pragmatic approaches to clinical trial design, overlapping scientific and ethical concerns related to eligibility criteria, and questions for further study. (shrink)