ELSIcon2022 • Paper • May 31, 2022
Claudia Azuelos, Anne-Marie Laberge
Background: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are diagnostic tests for rare genetic diseases. Studies use clinical utility to report on their clinical impacts.
Objective: To establish how clinical utility is defined in studies evaluating the impacts of WES/WGS results for pediatric patients.
Methods: Using appropriate search terms, relevant articles were identified in PubMed, Medline, Embase, and Web of Science. Eligibility was limited to studies about clinical utility of WES/WGS for pediatric patients published before 2021. Other relevant articles were added based on selected articles’ references. Articles were coded to assess definitions and measures of clinical utility.
Results: Of 1345 articles, 84 articles reported on the clinical utility of WES/WGS in pediatric patients. Clinical utility was not clearly defined in 19% of studies and 88% did not use an explicit measure of clinical utility. When present, definitions of clinical utility diverged from the usual definition focusing on changes in management to improve health outcomes, and included definitions limited to the diagnostic yield of WES/WGS or broadened to include decisions about withdrawal of care/palliative care and impacts on other family members.
Conclusions: Clinical utility is used to guide policy and practice decisions about test use. The lack of a standard definition of clinical utility of WES/WGS may lead to under- or overestimations of clinical utility, complicating policymaking. Broadening the definition to add elements such as decisions about withdrawal of care and impact on other family members, raises ethical issues of non-maleficence and justice.