Unraveling non-participation in genomic research: A complex interplay of barriers, facilitators, and sociocultural factors

Abstract

Although genomic research offering next-generation sequencing (NGS) has increased the diagnoses of rare/ultra-rare disorders, populations experiencing health disparities infrequently participate in these studies. The factors underlying non-participation would most reliably be ascertained from individuals who have had the opportunity to participate, but decline. We thus enrolled parents of children and adult probands with undiagnosed disorders who had declined genomic research offering NGS with return of results with undiagnosed disorders (Decliners, n = 21) and compared their data to those who participated (Participants, n = 31). We assessed: (1) practical barriers and facilitators, (2) sociocultural factors-genomic knowledge and distrust, and (3) the value placed upon a diagnosis by those who declined participation. The primary findings were that residence in rural and medically underserved areas (MUA) and higher number of barriers were significantly associated with declining participation in the study. Exploratory analyses revealed multiple co-occurring practical barriers, greater emotional exhaustion and research hesitancy in the parents in the Decliner group compared to the Participants, with both groups identifying a similar number of facilitators. The parents in the Decliner group also had lower genomic knowledge, but distrust of clinical research was not different between the groups. Importantly, despite their non-participation, those in the Decliner group indicated an interest in obtaining a diagnosis and expressed confidence in being able to emotionally manage the ensuing results. Study findings support the concept that some families who decline participation in diagnostic genomic research may be experiencing pile-up with exhaustion of family resources - making participation in the genomic research difficult. This study highlights the complexity of the factors that underlie non-participation in clinically relevant NGS research. Thus, approaches to mitigating barriers to NGS research participation by populations experiencing health disparities need to be multi-pronged and tailored so that they can benefit from state-of -the art genomic technologies.

Keywords: disparities; exome and genome sequencing; genetic counseling; genomic research; parent; underrepresented populations.

Figure 1A:. Recruitment and retention of Decliners from the UDN and DRSC

Illustration of sample identification, recruitment and study completion for the Decliner group. Recruited subjects were more willing to complete the qualitative interviews (47/52= 90%), than the quantitative surveys (21/52= 40%). There were no duplicate responses to either the surveys or the interviews in the Decliner group, with the data thus being independent.

Figure 1B:. Recruitment and retention of Participants from the UDN

Illustration of sample identification, recruitment and study completion for Participant group. Survey completion rate was higher than in the Decliner group (24/44 probands, 54.5%). Of the 24 probands in the Participant group, seven had duplicate survey responses, due to both parents responding, with a total of 31 responders (3 adult probands who responded for themselves and 28 guardians responding for the other 21 probands). Thus, non-independence of the data was accounted for in our analyses. Interviews were not performed in the Participant group, to decrease study burden, since they had already participated in the research NGS.

Figure 2:. Many individual barriers were endorsed by the Decliner group, reflecting significant group differences in both practical considerations and cultural factors

Multiple co-occurring barriers were endorsed by the Decliner group. Means (s.d.) of these barriers from the Barriers and Facilitators Checklist (Likert response options ranged from 1–7) are presented.