Role of 'virtual’ biopsies in oncology clinical trials: The potential to resolve ethical conundrums of research biopsies

Abstract: Often clinical trials incorporate biopsies conducted purely for research purposes (termed a “research purposes-only biopsy”, RPOB). RPOBs can be mandatory or optional; can support primary, secondary, or exploratory endpoints; do not influence clinical care; and may carry additional risk beyond the experimental treatment. Some oncology clinical trials, such as those for experimental breast cancer treatment protocols, include RPOBs. There are a range of professional opinions on the appropriateness of RPOBs, incorporating contexts of scientific and medical rationale, morality, and ethical principles such as informed consent. The American Society of Clinical Oncology has published an ethical framework for the use of RPOBs in oncology clinical trials. This framework, applied to breast oncology clinical trials, suggests that core-needle RPOBs of the breast may have a range of ethical acceptability, including unacceptable when mandatory and used for exploratory endpoints, and potentially unacceptable when mandatory and used for secondary endpoints. Noteworthy is that many oncology clinical trial protocols also include medical imaging conducted at several points during the trial period, and these imaging studies can be used for ‘virtual’ biopsies, i.e., imaging-based quantitative measures that non-invasively characterize anatomy and physiology and can predict treatment response and other clinical trial endpoints via machine learning and artificial intelligence methods. We present an overview of the use of RPOBs in breast oncology clinical trials, particularly in terms of associated research findings derived from the RPOBs, and a framework for evaluating if a ‘virtual’ biopsy from medical imaging can reasonably resolve RPOB ethical concerns in the study design.

Maryellen Giger, PhD – A.N. Pritzker Distinguished Service Professor, Radiology, University of Chicago