How are uncertain genomic test results experienced and negotiated by patients and families?

How are uncertain genomic test results experienced and negotiated by patients and families? A mixed-methods study incorporating observations and qualitative interviews

Background:
The field of genetic testing for the diagnosis of rare diseases has been marked by a rapid succession of technological advances, including most notably next generation sequencing. Despite the diagnostic advantages of exome and genome sequencing in the clinical setting, testing has created additional challenges by revealing uncertain results. These uncertainties include a diagnosis that contains uncertain prognosis and/or probability; an unexpected diagnosis that may or may not be related to the reason the testing was performed (secondary findings); or ‘variants of uncertain significance’, where the genetic variant identified cannot be classified as either pathogenic or benign (1). These types of results can be challenging for patients and families who usually enter into genetic testing for clear, definitive information to guide clinical and behavioural decisions (2). Questions exist around whether uncertain results should be reported to patients, the optimal strategies for communicating uncertain results to patients, and the consequences of uncertain genomic test results for patients, family members, health professionals and the healthcare system (3-4). 

Aims/Objectives:
The aim of this qualitative study is to explore the experience of patients and families receiving genomic test results that have an element of uncertainty. The key objectives are:

1) A systematic review to explore the experiences of patients and families receiving uncertain genomic test results;
2) Observations (audio-recordings and field notes) of patients and families receiving uncertain genomic test results in the clinical setting;
3) Qualitative follow-up interviews with patients/families soon after the return of results appointment to understand their experience of receiving uncertain results (e.g. what they understand their result to mean for them and their family, was it the result they expected, their reflections on the communication process, whether the results report matched what they had understood during the appointment);
4) Qualitative interviews with patients/families 6 months after receiving uncertain results to explore the clinical, behavioural an psychosocial impact of receiving uncertain results (e.g. how the result was discussed with family members; how an uncertain result has impacted them and the wider family; whether and how clinical care has changed; whether the results has had an wider impact such as school, benefits, anxiety etc);
5) Development of recommendations for practice regarding engaging and communicating with patients/families about uncertain results. 

Methods:
The student will gain experience of conducting ethnographic observations as well as semi-structured interviews. The student will gain experience of qualitative data analysis including how to triangulate data across multiple methods and data sources. 

Timeline:
Year 1: Study set-up (NHS Ethics and R&D), systematic review;
Year 2: observations and interviews;
Year 3: analysis and write-up. 

References:
1. Han, P. K. J., K. L. Umstead, B. A. Bernhardt, R. C. Green, S. Joffe, B. Koenig, I. Krantz, L. B. Waterston, L. G. Biesecker and B. B. Biesecker (2017). "A taxonomy of medical uncertainties in clinical genome sequencing." Genetics In Medicine 19: 918.
2. Newson, A. J., S. J. Leonard, A. Hall and C. L. Gaff (2016). "Known unknowns: building an ethics of uncertainty into genomic medicine." BMC Med Genomics 9(1): 57.
3. Biesecker, B. B., W. Klein, K. L. Lewis, T. C. Fisher, M. F. Wright, L. G. Biesecker and P. K. Han (2014). "How do research participants perceive "uncertainty" in genome sequencing?" Genet Med.
4. Makhnoon, S., B. H. Shirts and D. J. Bowen (2019). "Patients' perspectives of variants of uncertain significance and strategies for uncertainty management." J Genet Couns.