Ethics and Collateral Findings in Pragmatic Clinical Trials.

Pragmatic clinical trials (PCTs) offer important benefits, such as generating evidence that is suited to inform real-world health care decisions and increasing research efficiency. However, PCTs also present ethical challenges. One such challenge involves the management of information that emerges in a PCT that is unrelated to the primary research question(s), yet may have implications for the individual patients, clinicians, or health care systems from whom or within which research data were collected. We term these findings as ?pragmatic clinical trial collateral findings,? or ?PCT-CFs?. In this article, we explore the ethical considerations associated with the identification, assessment, and management of PCT-CFs, and how these considerations may vary based upon the attributes of a specific PCT. Our purpose is to map the terrain of PCT-CFs to serve as a foundation for future scholarship as well as policy-making and to facilitate careful deliberation about actual cases as they occur in practice.

Choices for return of primary and secondary genomic research results of 790 members of families with Mendelian disease.

Although consensus is building that primary (PR) and secondary findings (SF) from genomic research should be offered to participants under some circumstances, data describing (1) actual choices of study participants and (2) factors associated with these choices are limited, hampering study planning. We conducted a cross-sectional analysis of choices made for return of PR and SF during informed consent by members of the first 247 families (790 individuals) enrolled in the Baylor-Hopkins Center for Mendelian Genomics, a genome sequencing study. Most (619; 78.3%) chose to receive SF and PR, 66 (8.4%) chose PR only, 65 (8.2%) wanted no results, and 40 (5.1%) chose SF only. Choosing SF was associated with an established clinical diagnosis in the proband (87.8 vs 79%, P=0.009) and European ancestry (EA) (87.7 vs 73%, P<0.008). Participants of non-European ancestry (NEA) were as likely as those of EA to choose SF when consented by a genetic counselor (GC) (82% NEA vs 88.3% EA, P=0.09) but significantly less likely when consented by a physician (67.4% NEA vs 85.4% EA, P=0.001). Controlling for proband diagnosis, individuals of NEA were 2.13-fold (95% CI: 1.11-4.08) more likely to choose SF when consented by a GC rather than a physician. Participants of NEA were 3-fold more likely than those of EA to decline all study results (14.7% NEA vs 5.4% EA, P<0.008). In this ethnically diverse population, whereas most participants desired PR and SF, more than 20% declined some or all results, highlighting the importance of research participant choice.