A Randomized Non-Inferiority Trial of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Cancer (eREACH2)

Abstract

BackgroundMany at-risk patients lack access to genetic services due to a genetic counselor (GC) workforce shortage. Little is known about how digital alternatives impact patients with and without cancer who meet criteria for genetic testing. MethodseREACH2 is a randomized 4-arm non-inferiority trial where pre-test (visit 1) and/or return of results (visit 2) GC counseling was replaced with a patient-centered digital intervention. Arms include: A (GC/GC), B (GC/digital), C (digital/GC) and D (digital/digital). Primary outcomes were non-inferiority in uptake of genetic services and change in genetic knowledge and general anxiety from baseline to post-disclosure of results (T0-T2). Secondary cognitive and affective outcomes were assessed using non-inferiority ANOVAs and equivalency chi-squared tests in intention-to-treat and per-protocol analyses. Findings773 participants were recruited nationwide; 46.6% from rural areas. Mean age was 51 years (range 20-87), 13% male, 12% non-white, 29% had less than a college education, and 33% had a personal history of cancer. 584 (76%) patients completed testing (14% had a positive result, 16% had a VUS). In the primary ITT analyses, we met the non-inferiority for uptake of genetic services and anxiety, but results were inconclusive for knowledge. Secondary outcomes were heterogeneous across arms. Arm C demonstrated consistently favorable effects, while Arms B and D showed less favorable outcomes in select domains (e.g. satisfaction and MICRA). Patients who received positive or VUS results via digital disclosure had significantly higher MICRA scores -- indicating greater negative response to testing. InterpretationIn this large, randomized trial of patients with and without cancer, the eREACH intervention was effective for pre-test counseling, but inconclusive for digital disclosure of results. Exploratory analyses suggest that digital delivery could be a reasonable alternative for individuals receiving negative results, while those receiving positive or VUS results may derive some short-term psychosocial benefit from GC disclosure.