title: The misguided ethics of crossover trials.
abstract: Crossover is increasingly favored in trials of cancer therapies; even those that seek to establish the basic efficacy of novel drugs. Crossover is done in part for trial recruitment, but also out of a sense of doing the right thing-offering the investigational agent to more patients. In this paper, we argue that this ethical inclination-that crossover is a preferred trial choice-is misguided. In seeking to sate the desires of participants, we might undermine a trial's ability to answer a meaningful clinical question. When a trial is incapable of answering a question, it becomes unethical. Using a crossover strategy in oncology clinical trials can make trials less ethical, not more.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr. 10/12N226, Bethesda, MD 20892, United States. Electronic address: vinayak.prasad@nih.gov.
authors.forename: Vinay
authors.initials: V
authors.lastname: Prasad
authors.affiliation: Department of Bioethics Clinical Center, National Institutes of Health, 10 Center Dr. 10/1C118, Bethesda, MD 20892, United States. Electronic address: CGrady@cc.nih.gov.
authors.forename: Christine
authors.initials: C
authors.lastname: Grady
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000941:ethics* / Q000379:methods*; D018592:Cross-Over Studies; D015507:Drugs, Investigational; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational
keywords: Crossover; Ethics of clinical trials; Trial validity