Written communication of whole genome sequencing results in the NHS Genomic Medicine Service: a multi-centre service evaluation

Abstract

Whole genome sequencing (WGS) is being used in diagnostic testing for certain clinical indications within the NHS Genomic Medicine Service (GMS) in England. Letter writing is an integral part of delivering results. However, no national guidelines for writing results from WGS exist. This multi-centre service evaluation used mixed methods to understand the content and readability of letters returning diagnostic, variant of uncertain significance (VUS), and no-finding results to paediatric rare disease patients. Eight Regional Genetics Services (response rate 47%) in England provided a total of 37 letters returning diagnostic (n = 13), VUS (n = 10), and no-finding (n = 14) results. Diagnostic and VUS results were usually delivered during an appointment; no-finding results were typically delivered by letter only. Letters were diverse in which content topics they covered and level of detail. No-finding letters (14/14) explained the result but were less likely to cover other topics. Diagnostic letters discussed the result (13/13), the condition (13/13), clinical genetics follow-up (13/13), clinical management (10/13), and adapting to the result (9/13). VUS letters explained the result (10/10), diagnostic uncertainty (10/10), and clinical genetics follow-up (10/10). Uncertainty was a common component of letters (33/37), irrespective of the result. Reanalysis or review after one or more years was suggested in 6/13 diagnostic, 7/10 VUS, and 6/14 no-finding letters. The mean reading level of letters corresponded to 15-17 years. Understanding how WGS results are conveyed to families during appointments, as well as how families interpret that information, is needed to provide a more comprehensive overview of results communication and inform best practices.

Fig. 1. A circle map summarising the relative frequency at which content topics were included in patient letters returning whole genome sequencing results.

The circle map is divided into letters returning diagnostic results (n=13), VUS results (n=10), and no-finding results (n=14). Within each division, topics in the inner most circle were included in 100% of letters returning that result type; topics in the second circle from the centre were included in 80-100% of letters; topics in the third circle from the centre were included in 50-80% of letters; and topics in the outer most circle were included in <50% of letters.

Fig. 2. The type and frequency of clinical genetics follow-up described in letters returning whole genome sequencing results.

Follow-up reported in (a) diagnostic result letters, (b) variants of uncertain significance result letters, and (c) no-finding result letters.