BRCA-DIRECT: piloting a digital platform enabling clinically-integrated, clinician-independent, rapid, genetic susceptibility biomarker testing

Background Germline BRCA biomarker status is an incontrovertibly powerful biomarker of cancer risk enabling identification of individuals at very high risk of cancer in whom measures for primary and secondary cancer prevention are particularly impactful.

Despite dramatic advances in sequencing technologies and commensurate price drop, current NHS gBRCA1/BRCA2 biomarker testing continues to fail clinicians and patients by being slow, labour-intensive, expensive and thus of necessarily highly restricted availability. Patients are increasingly resorting to poorly regulated direct-to-consumer testing.

Aims Pilot delivery of the BRCA-DIRECT digital platform demonstrating feasibility, acceptability and safety of ‘Clinically-Integrated, Clinician-Independent Rapid, Digital, Genetic Susceptibility Biomarker Testing’ (CICIRDGSBT) for testing gBRCA1/BRCA2/PALB2 status. Methods 1.

In consultation with clinicians and patients, development of written, animation and video content for pre-test digital information delivery 2.

In collaboration with a commercial software provider, development and user-testing of the BRCA-DIRECT platform and user-interface for end-to-end digital gBRCA1/BRCA2 biomarker testing and pathway management. 3.

Piloting of the BRCA-DIRECT platform to deliver CICIRDGSBT in 700 patients with newly diagnosed breast cancer to test pathway logistics and assess operational outcomes. 4.

Pilot study comparing BRCA-DIRECT to conventional 1:1 clinician-delivered communication in 300 patients to evaluate comparability of BRCA-DIRECT for efficacy (patient knowledge), patient psychological acceptability (anxiety) and process acceptability (uptake and satisfaction) Outputs 1.

Digital platform and user interface (BRCA-DIRECT) designed, piloted, adapted and optimised with clinical and patient user-communities 2.

Pilot data from two centres testing and demonstrating pathway feasibility of BRCA-DIRECT for BRCA-positive and BRCA-negative patients 3.

Pilot data from comparison to conventional 1:1 clinician-delivered communication for patient-reported measures of efficacy (patient knowledge), patient psychological acceptability (anxiety) and process acceptability (uptake and satisfaction), providing preliminary evidence of non-inferiority and accurate baseline estimates by which to proceed to a largescale implementation study 4.

Cultural transformation from conventional ‘1:1 clinician-delivered genetic counselling’ to ‘clinically-integrated but clinician-independent digital information delivery’ via strong leadership and wide engagement of clinical genetics and oncology specialties in national consultative clinical and implementation groups. 5.

Pathway to largescale implementation study and NHS adoption, via active participation as collaborators of senior leadership of NHSE and devolved nation healthcare services. 6. 1000 participants with breast cancer benefit from BRCA-testing, offering opportunity for secondary cancer prevention, molecularly stratified therapy and primary prevention in family members, or important reassurance if BRCA-negative