A randomized study of digital versus genetic counselor return of actionable genetic research results to biobank participants (RESPECT3 study)

There is consensus that research participants should be informed about plans for return of genetic research results. However, best practices for return of results in large biobank and cohort studies do not exist currently, and how best to communicate actionable genetic research results remains unclear. While having genetic counselors disclose these results may be ideal to ensure understanding, minimize distress, and optimize medical follow-up, genetic counselor (GC) workforce shortages and costs are barriers. The RESPECT3 study evaluates whether digital delivery alternatives for pre-disclosure education and return of actionable genetic research results is non-inferior to remote telehealth disclosure by a genetic counselor. The RESPECT3 Study is a hybrid type 1 effectiveness-implementation study which evaluates digital alternatives for pre-disclosure education and return of actionable research results in randomized non-inferiority trial. The return of results process in RESPECT3 uses a two-step process. In step one, participants with an actionable result and procedural controls (no actionable result) are invited to digital pre-disclosure education and provided options for opting out of results. In Step 2, those with actionable results who have not opted out are randomized to receive results via a digital disclosure intervention (digital-ROR) or with a GC. Participants include English-speaking adults who enrolled in the Penn Medicine BioBank (PMBB) and have an actionable research result according to the ACMG secondary findings list. The primary outcomes are non-inferiority of knowledge and disease specific distress (cancer and cardiovascular disease) after receipt of research results. Uptake of research results is a secondary non-inferiority outcome. Confirmatory clinical testing is covered by the study and all participants with confirmed results are referred to the appropriate clinical genetic program for clinical recommendations. The RESPECT3 study is expected to provide critical empiric data on the effectiveness of using digital alternatives for pre-disclosure education and return of genetic research results in a representative clinical population of research participants who enrolled in an institutional biobank where return of results was not the focus of the study. Equally important, our theoretically-informed process evaluation data is expected to inform modifications to identify barriers and facilitators to broader implementation. NCT04242667.