CHARGE free cascade genetic testing: Effectiveness and implementation outcomes from a hybrid type I feasibility trial

Direct contact of relatives as a strategy for cascade genetic testing is demonstrably more efficacious compared to proband-mediated testing. However, clinical implementation is limited because of unaddressed testing cost. This study tested a choice architecture based direct-contact strategy leveraging free tests offered by laboratories in a randomized hybrid type-I effectiveness implementation feasibility trial.

Eligible relatives were randomized at the proband level to receive CHARGE intervention (direct contact and education about free testing window) or usual care with mixed-methods evaluation.

Of the 194 patients with pathogenic variants, 28 consented and completed a baseline survey, referring 97 relatives who were randomized. On average, probands (82% female, 64% White) referred 3.4 relatives each. Relative-reported cascade testing rate was 53% (8/15) in intervention and 22% (2/9) in control. In adjusted multilevel regression, intervention relatives had higher odds of undergoing testing compared to control (adjusted odds ratio=7.7, p=0.04). CHARGE reached 23% (28/122) of all eligible probands. Proband and relative acceptability of the study procedures were high.

A direct-contact cascade testing intervention using free tests from laboratories was feasible to implement, effective at increasing cascade testing, acceptable to both relatives and probands, but clinically integrated recruitment approaches may be necessary.