Title: A study to define patient priorities and preferences when consenting to whole genome sequencing to ensure informed choice
Funder: Department of Health and Social Care

Abstract: Background: Advances in sequencing technologies mean that whole genome sequencing (WGS) is likely to become a routine testing tool in the NHS to diagnose conditions, predict and prevent disease and provide personalised medical treatments. Currently, there is very little empirical evidence reporting the attitude and experience of patients undergoing WGS. Critical areas which lack evidence are whether patients undergoing WGS are making an informed decision, and what support and information is required in order to ensure this happens. Aim: The key question this study will address is: What is best practice to ensure patients make informed decision for WGS in NHS care? Plan of investigation: This will be a longitudinal mixed methods study utilising questionnaires, interviews and audio-recordings of the consent process and results disclosure. The study cohort will be recruited from individuals with cancer and rare diseases, enrolled into the 100,000 Genomes Project. Questionnaires will include validated psychological measures of informed consent, psychological wellbeing and decisional satisfaction and regret. These will be conducted at two time-points; 1) following consent (or declining) for WGS and 2) 12-18 months after enrolment. We will aim to collect 500 questionnaires at T1 to ensure precision of informed consent within at least +/- 4.47% with 95% confidence. Interviews (40) will also be conducted at both time-points and will explore patients attitudes towards WGS including expectations, motivations for accepting, experience of the consent process including how this could have been improved, feedback and interpretation of results and perceived value of WGS. Interviews (40) will also be conducted with health professionals to explore their experience of discussing and consenting patients to WGS, and feeding back test results. Audio-recordings (40) of the consenting process and result disclosure will also take place to provide in vivo data on how WGS is discussed and what questions arise. The study design and questionnaires/interview topics will be developed through consultation with an advisory team of patient advocates, genetics and clinical experts who have been delivering genetic services in the NHS, who will help guide the project throughout its lifetime. Key outcomes will be the development of recommendations regarding how patients should be consented for WGS as it is implemented into clinical practice as well as consent support packs for healthcare professionals. Summary of potential benefits to patients and NHS: This research will have implications for clinical service as we will identify whether patients are making informed decisions to undergo WGS, how informed consent can be best facilitated, what the barriers are to informed consent and how these can be addressed. Particular focus will be given to facilitating informed consent amongst minority ethnic groups. The findings from this research will form the basis of recommendations for health policy makers and used to develop a consent support pack for clinicians. These outputs will ensure a swift trajectory from research to patient benefit by delivering actionable findings regarding the consent process which can be adopted without delay. These deliverables will be underpinned and shaped by the views and experiences of key stakeholders including patients and health professionals with first-hand experience of consenting to WGS. This research will be disseminated through academic high-profile publications, conferences (academic and patient groups), as well as to policy makers in NHS England and the Department of Health (in the form of a summary document which lists the recommendations). A public meeting will also be help to disseminate the findings more widely.

Lay abstract: Whole genome sequencing (WGS), in which an individual s DNA is sequenced to determine the genetic cause of disease, is set to transform the way genetic testing is offered in the NHS. Whilst some research has been conducted around the patient consent process there is very little information on whether patients are in fact making an informed decision to have (or decline) WGS, and if not, how this can be improved. The aim of this research is to address this gap by exploring the views and experiences of patients and relatives consenting to WGS as part of the 100,000 Genomes Project. This study will include questionnaire and interviews (at the consent point and 12-18 months later) and audio-recordings of consultations. Questionnaires will measure informed consent, psychological impact and decisional satisfaction. Interviews will explore attitudes and motivations for accepting WGS, the consent process, interpretation of results and perceived value. Interviews will also be conducted with health professionals to explore their experience of discussing WGS, consenting patients and delivering results. Audio-recordings of the consent discussion and feedback of results will provide first-hand evidence of what questions arise and how WGS is discussed. The study design and questionnaire/interview topics will be developed through consultation with an advisory team of patient advocates, genetics and clinical experts who will guide the project throughout its lifetime. This research will directly benefit patients and inform clinical practice by developing recommendations for how WGS should be offered in the NHS as well as the development of consent support packs for professionals. These will be underpinned by the views and experiences of patients and health professionals with first-hand experience of WGS and disseminated to NHS commissioners, clinicians, patient groups and other health policymakers to ensure a tailored and tested approach. Findings will also be disseminated through publications and conferences.

Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: GENERIC HEALTH RELEVANCE