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

Direct contact of relatives is more effective than proband-mediated notification for cascade testing, but test cost hinders implementation. This randomized hybrid type-I trial tested a direct-contact strategy (with information on a window of free testing offered by laboratories) against usual care. Of 194 patients with pathogenic variants, 28 consented (23% of eligible probands reached) and referred 97 randomized relatives, 3.4 on average per proband. Relative-reported cascade testing was 53% (8/15) in the intervention arm versus 22% (2/9) in the control arm (adjusted OR 7.7; p = 0.04), with high acceptability.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The signal is favourable, but it rests on 24 responding relatives (15 and 9) and on self-reported testing: this is a feasibility trial, not a demonstration of efficacy. Only 23% of eligible probands were reached, and it is this recruitment step, more than test cost, that limits deployment. Worth noting for cascade-testing programmes, with no bearing on variant interpretation.

Analysis by Dr Thibaut Benquey