Work

When Ethics Constrains Clinical Research: Trial Design of Control Arms in “Greater Than Minimal Risk” Pediatric Trials

Year: 2011

Type: article

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. In this article, the authors debate the real and apparent conflicts between scientific and ethical considerations surrounding the choice of controls in randomized clinical trials for rare and fatal diseases affecting children. The authors point out that when nonrandomized clinical trials are proposed as reasonable alternatives, there is still an unfortunate tendency to think of these alternatives as inferior.

Source: Human Gene Therapy

DOI: 10.1089/hum.2010.230

Authors: Inmaculada de Melo-Martín, Dolan Sondhi, Ronald G. Crystal

Institution: Weill Cornell Medicine

Language: English

Topic: Ethics in Clinical Research

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of Neurological Disorders and Stroke, National Center for Research Resources