ELSIcon2022 Flash: Revisiting the ethics of secondary findings in diagnostic genome-wide sequencing

ELSIcon2022 • Flash • May 27, 2022

Michael Mackley

Secondary findings (SF) in genome-wide sequencing are variants unrelated to the indication for testing but associated with medically actionable health risks. Despite a vibrant debate around their management starting nearly one decade ago, policy variation persists to this day. During this period, much evidence—both qualitative and quantitative—relevant to the management of SF has been gathered, and large numbers of SF have been returned to patients. In light of this, many of the arguments driving the debate around SF have changed. Some early issues are more settled, such as those related to autonomy, with consensus reached around an opt-out approach. Other concerns, such as the potential for psychological harm, have not been borne out. Concepts of utility and gene lists remain inconsistent, with institutions around the globe—all with different resources and philosophies—offering varying options and results to participants. Finally, as patients receive SF and undergo subsequent evaluation, estimates of penetrance are being refined and the impacts of these variants are coming to light.
Previously, many health centres outsourced genome-wide sequencing, following policies at the laboratory of choice. However, as sequencing costs continue to drop, and as genome-wide approaches become increasingly first-line, many institutions are undertaking sequencing locally. Thus, policy around SF management has moved from the international stage to the local level. This timely review will consider the arguments influencing early debates around secondary findings, explore the evidence that has been generated since, and trace early debate through to the arguments and evidence gaps that exist today.