Considering Usual Medical Care in Clinical Trial Design

Abstract

In 2002, a clinical trial designed to evaluate optimal ventilation practice [1],[2] for patients with acute respiratory distress syndrome (ARDS) sparked a major controversy. Critics charged that management of ARDS in the different arms of the study did not adequately reflect usual medical care, and alleged that it was essential for scientific and ethical reasons to have a usual care comparison arm in the study. The controversy over trial design enmeshed the National Institutes of Health (NIH), the Office for Human Research Protections (OHRP) and the critical care research community. The trial was put on hold and reviewed by two independent expert panels. Experts pointed to the need for further analysis of the scientific and ethical issues involved in choosing trial designs when there is no consensus on standard of care. In November 2005, NIH and a number of other federal agencies sponsored a meeting (see Text S1) to discuss clinical trial design challenges involving selection of usual care comparison groups (Text S1). The meeting was informed by a background paper (Text S1) outlining types of challenges involved in selecting usual care arms, prepared by a working group with expertise in clinical trial design, ethics, evidence-based medicine, statistics, and science policy. We present here the background framework and case studies used in this paper (Text S1). We enumerate five factors that make consensus on these issues particularly difficult, and recommend specific criteria for assessing proposed study designs. Terminology Terms such as “standard of care,” “control arm,” “usual care,” and “community care” have all been used to describe arms reflecting conventional therapy. We use the term “usual care” to describe the care commonly given by practitioners in a community to avoid any legal or normative implications of the term “standard of care.”