When ethics constrains clinical research: trial design of control arms in "greater than minimal risk" pediatric trials.

Publication Type	Academic Article
Authors	de Melo-Martín I, Sondhi D, Crystal R
Journal	Hum Gene Ther
Volume	22
Issue	9
Pagination	1121-7
Date Published	05/19/2011
ISSN	1557-7422
Keywords	Controlled Clinical Trials as Topic, Genetic Therapy, Research Subjects
Abstract	For more than three decades clinical research in the United States has been explicitly guided by the idea that ethical considerations must be central to research design and practice. In spite of the centrality of this idea, attempting to balance the sometimes conflicting values of advancing scientific knowledge and protecting human subjects continues to pose challenges. Possible conflicts between the standards of scientific research and those of ethics are particularly salient in relation to trial design. Specifically, the choice of a control arm is an aspect of trial design in which ethical and scientific issues are deeply entwined. Although ethical quandaries related to the choice of control arms may arise when conducting any type of clinical trials, they are conspicuous in early phase gene transfer trials that involve highly novel approaches and surgical procedures and have children as the research subjects. Because of children's and their parents' vulnerabilities, in trials that investigate therapies for fatal, rare diseases affecting minors, the scientific and ethical concerns related to choosing appropriate controls are particularly significant. In this paper we use direct gene transfer to the central nervous system to treat late infantile neuronal ceroid lipofuscinosis to illustrate some of these ethical issues and explore possible solutions to real and apparent conflicts between scientific and ethical considerations.
DOI	10.1089/hum.2010.230
PubMed ID	21446781
PubMed Central ID	PMC3177948