Two-step offer and return of multiple types of additional genomic findings to families after ultrarapid trio genomic testing in the acute care setting: a study protocol

Abstract

IntroductionAs routine genomic testing expands, so too does the opportunity to look for additional health information unrelated to the original reason for testing, termed additional findings (AF). Analysis for many different types of AF may be available, particularly to families undergoing trio genomic testing. The optimal model for service delivery remains to be determined, especially when the original test occurs in the acute care setting.Methods and analysisFamilies enrolled in a national study providing ultrarapid genomic testing to critically ill children will be offered analysis for three types of AF on their stored genomic data: paediatric-onset conditions in the child, adult-onset conditions in each parent and reproductive carrier screening for the parents as a couple. The offer will be made 3–6 months after diagnostic testing. Parents will have access to a modified version of the Genetics Adviser web-based decision support tool before attending a genetic counselling appointment to discuss consent for AF. Parental experiences will be evaluated using qualitative and quantitative methods on data collected through surveys, appointment recordings and interviews at multiple time points. Evaluation will focus on parental preferences, uptake, decision support use and understanding of AF. Genetic health professionals’ perspectives on acceptability and feasibility of AF will also be captured through surveys and interviews.Ethics and disseminationThis project received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. Findings will be disseminated through peer-review journal articles and at conferences nationally and internationally.

Eliciting parental preferences and values for the return of additional findings from genomic sequencing

“…Our study identified a high expected uptake rate of AF (93%). While there may be multiple factors influencing AF uptake rates 12 , emerging evidence suggests that rates may range between 80% and 98% 13 – 15 . A Canadian study by Regier et al 16 , elicited societal preferences for the return of AF from genomic sequencing using a discrete-choice experiment method.…”

“…Our work benefited from a national recruitment of families with children affected by rare conditions through the Australian Genomics and Melbourne Genomics programs. The two-step offer for AF analysis model has been argued to offer the advantage of a temporal separation of the AF offer from the offer of diagnostic testing, which reduces families’ decision burden during a period of high distress, while providing the opportunity to receive more information and reflect on the risks and benefits of the analysis for AF 12 , 19 . Building on this principle, we provided in-depth information about AF through the adapted version of Genetics Adviser 20 , to further enhance the formation of preferences and support informed choice responses.…”

“…Parents of children with a suspected rare condition were recruited into disease-specific flagship studies (e.g., brain malformations, cardiomyopathies, renal conditions, immunodeficiencies) through Australian Genomics 2 , 3 and Melbourne Genomics Health Alliance 22 between 2016–2021. For this survey, parents of children recruited into rare-disease flagships who had consented to secondary research as part of their original research consent were invited to participate, in line with the two-step offer and return of additional genomic findings model, which separates AF analysis from the initial episode of diagnostic testing 12 , 19 . Parents were not offered to receive AF when they had the testing done for their child.…”

“…The survey then listed risks and benefits from the return of AF with respect to treatment, future health conditions, personal and family impacts. The background information on AF represented a modified version of Genetics Adviser 20 , developed for the Australian Genomics Acute Care Genomics Programme Additional Findings substudy 12 .…”

Are We Ready for Whole Population Genomic Sequencing of Asymptomatic Newborns?

“…This kind of staged approach has been used in other settings where GS is being used in time-critical settings to obtain a diagnosis and secondary information is offered a few months after the initial testing. 37 …”