By Susan M. Wolf & Wylie Burke
Translational genomics challenges the traditional view that research and clinical care are distinct activities that should be governed by separate norms, rules, and law. Beginning with the Belmont Report and emergence of regulations governing the conduct of research with human participants, the conventional view has been that there are fundamental differences between research and clinical care, necessitating distinctive ethical frameworks, regulatory oversight, and legal analyses.
However, a new paper published in Genetics in Medicine reports the first empirical test of this conventional dichotomy in the context of genomics. The paper analyzes empirical data collected by surveying investigators conducting major NIH-funded genomics research projects in the NHGRI/NCI-supported Clinical Sequencing Exploratory Research (CSER) Consortium. Those investigators report their actual practices, experiences, and attitudes in navigating the research-clinical interface. These results reveal how the research-clinical boundary operates in practice and cast serious doubts on the adequacy of the conventional dichotomy.
The CSER Consortium includes 9 NIH-funded U-award projects investigating translation of genomic sequencing into clinical care. A 16-person working group led by Susan Wolf, JD, at the University of Minnesota and Wylie Burke, MD, PhD, at the University of Washington developed a 22-item survey to investigate how the CSER projects were conceptualizing and navigating the research-clinical interface. All 9 U-award projects participated. Descriptive data were tabulated and qualitative analysis of text responses identified themes and characterizations of the research-clinical interface.
Survey responses described how studies approached this interface, including in consent practices, recording results, and using a research vs. clinical laboratory. Analysis of the survey responses revealed four characterizations of the interface, which arrayed along a spectrum: (1) clear separation between research and clinical care; (2) interdigitation of the two with steps to maintain separation; (3) a dynamic interface, with case-by-case negotiation of where to draw the line between research and clinical care; and (4) merging of the two domains. These characterizations did not appear to be mutually exclusive to the investigators; all survey respondents used at least two different characterizations in addressing survey questions. Though research has traditionally been differentiated from clinical care, and respondents acknowledged elements of translational research (such as consent procedures and the location of research vs. clinical activities) designed to differentiate the domains, respondents also pointed to factors blurring the distinction.
These results illustrate the difficulty in applying the traditional bifurcation of research vs. clinical care to translational models of clinical research, including in genomics. The fact that most of the CSER studies described a merger of research and clinical care, at least in response to some survey questions, raises important questions about the conduct of such translational genomics studies.
First, this perceived merger challenges the conventional wisdom that while clinical care benefits patients, research seeks only generalizable knowledge. An important component of the merger for these studies was the return of research results that were, for at least some patient-participants, expected to contribute to clinical care. The perceived merger also raises the question of whether the IRB – an oversight body for research – is the right body to oversee what results are returned in these studies for the purposes of clinical care, especially when results are well-validated and clinically significant findings from a CLIA-certified lab.
Second, the translational merger of research and clinical care may also have implications for insurance coverage and malpractice liability exposure. Although both customarily attach only in domains of clinical care, the rapid progress of genomic research in establishing the significance of genomic variants in diagnosis and care calls for new mechanisms to support appropriate participant access while creating standards for responsible clinical implementation.
This paper shows that the traditional dichotomous approach is now part of a broader continuum of perspectives including merger of research and clinical care. This poses fundamental challenges to the conduct, ethics, and oversight of both research and clinical care in translational genomics.