Exome sequencing study in a clinical research setting finds general acceptance of study returning secondary genomic findings with little decisional conflict

Abstract

The return of individual genetic results from clinical research varies considerably by study (Wynn et al., 2015). This variability is partly dependent on study context, such as the relationship between investigator and participant, available resources, institutional norms, and investigator preference (Jarvik et al., 2014). For example, a genomic research study where physicians provide individual medical recommendations or administer treatment to participants has different ethical obligations than a research study doing genomic analysis on samples from de-identified biobank participants. One area without consensus is the return of secondary findings (SF) in a research setting (Wolf et al., 2015). Return of a selected consensus set of SF is recommended in the clinical setting by the American College of Medical Genetics and Genomics (ACMG) (Green et al., 2013;Kalia et al., 2017).One way to inform policy on the return of SF in the research setting is to conduct research on patient knowledge and preferences.In one study conducted at the National Institutes of Health (NIH) Clinical Center (CC), where the current study was also conducted,

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

“…Most participants reported either positive or neutral impacts of receiving results, both when they were related to the study and also for UF/SF [ 9 , 65 , 79 , 153 , 157 , 159 , 174 – 176 , 178 , 179 , 181 , 182 , 185 , 187 , 190 , 191 , 195 ]. A study of 17 research participants and family members who received UF showed that most (16/17) found the process mainly positive or useful and were thankful for being told they have the disease, both for their own wellbeing and also because it provides valuable knowledge for their children [ 153 ].…”

“…Clinical research context. Research participants generally expressed high interest in receiving UF, with values in most studies ranging from 61-100% depending on the nature of the UF [6,11,13,66,69,71,72,87,[153][154][155][156][157][158]. Although participants were keen to receive all types of UF [77,154,158,159], studies that asked respondents to specify which types of UF they wished to receive showed participants were most interested in receiving those that could have implications for their health [66,156].…”

Difficulties in disclosing secondary findings by facilities performing comprehensive germline genetic testing for rare diseases in Japan

“…The factor “to promote entry in research” was not considered important as a reason for disclosing SF (Figure 5A), indicating that the thirst for information was not possibly out of scientific interest but rather a reflection of anxiety. There has been considerable research abroad on what research participants think about SF disclosure 11–13 . In a study conducted with the parents of minor initiators, many parents reported that they would prefer to receive all the results obtained by exome analysis (variants related to a disease that is actionable in childhood, variants related to a disease that is not treatable or preventable in childhood, and carrier status for an autosomal recessive disorder).…”

“…There has been considerable research abroad on what research participants think about SF disclosure. [11][12][13] In a study conducted with the parents of minor initiators, many parents reported that they would prefer to receive all the results obtained by exome analysis (variants related to a disease that is actionable in childhood, variants related to a disease that is not treatable or preventable in childhood, and carrier status for an autosomal recessive disorder). Furthermore, parents have been reported to have the most positive attitudes toward learning about childhood-onset actionable variants and the most resistance to learning about adultonset non-actionable variants and recessive carriers of recessive gene.…”

Research participants' perspectives about the return of uninformative genomic test results in a clinical research setting

“…Although there is less of a moral imperative to return results from research testing than clinical testing (and therefore less consistency in researchers' return of result practices), the proportion of research studies that recognize a duty to return results is growing. Evidence suggests that most research participants find this acceptable or desirable (Bombard et al, 2019; Harrison et al, 2022; Kostick et al, 2019; Leppig et al, 2022; Similuk et al, 2021). Compared to clinical settings, research settings vary greatly with respect to reporting policies and methods for contacting and communicating sequencing results to patients (Fossey et al, 2018).…”