In summary, none of the studies identified evaluated WGS or WES in a screening context and, even when looking at WGS or WES in other clinical contexts, only 10 of the 86 included studies in the review were cost–utility analyses, which is the preferred outcome for the UK NSC cost-effectiveness evaluations. The majority of the included studies focused their time horizon or analyses solely on the diagnostic process, rather than incorporating any changes in patient management and the downstream cost and health consequences of these changes. Our review did identify some valuable micro-costing studies, which provide a detailed breakdown of the exact resource use required for WGS testing (see data extraction in Report Supplementary Material 5 for details of cost components for each study). These are likely to be useful for any future economic evaluations of WGS for newborn screening; however, there is likely to be additional infrastructure requirements to facilitate WGS testing at this scale to consider and possibly some economies of scale.
The public voice on evaluating whole genome sequencing
Patient and public involvement and engagement group reflections on the topic discussions
At the outset, the group largely supported WGS for newborn screening. There was some diversity of views underpinning this in terms of the way that participants viewed potential harms and benefits, but overall, the benefits were seen to outweigh any harms. As meetings progressed and the complexities were explored, views became more nuanced, for example, one participant mentioned that they now were ‘sitting on the fence a bit’. By the final meeting, there was still a sense of general positivity around the potential for WGS in newborns, but the group also articulated as many harms as benefits in the whiteboard exercise, illustrating their considered approach to balancing harms and benefits. Benefits identified included saving lives, improving outcomes and quality of life, a reduction in unnecessary and potentially invasive testing while searching for a diagnosis, information for future reproductive choices and enabling vigilance for the onset of symptoms. Harms identified included parental anxiety and unnecessary worry, the possibility of uncertainty rather than clarity resulting from test results, concerns around education of what screening results mean (both among the public and health professionals), questions of who owns the data and who they are shared with, the strain on health and support services and concerns around whether doctors will treat children as aggressively if the condition is thought to have a poor prognosis.
Reduction of harms focused on the provision of adequate support for parents and children (and children transitioning to adulthood), including emotional support, clear clinical pathways for diagnosis and treatment for babies identified as having a ‘condition suspected’ result, along with education on what screening results mean (including the possibility of uncertainty and the difference between a screening result and a diagnosis). Several group members reflected on poor experiences with receiving genetic diagnoses that led to harm, and in some cases, trauma, and they expressed the view that these issues with the current system must be addressed before any expansion of screening. Under the headings of ‘potential harms’ and ‘what should happen when the evidence is not available?’, several group members mentioned the option of targeted screening being a preferable approach, where results are only disclosed if they meet a threshold of confidence in the result. In these circumstances, it was suggested that the other data gathered could be used for research but that families should be notified if/when more became known about any uncertain findings.
Evaluation of the patient and public involvement engagement process
All participants engaged and participated in the process; they freely shared their views and experiences and openly listened to, and respected, the views of others. Participants responded that taking part was a positive experience. Some found it difficult to attend meetings due to other commitments (including caring commitments), and this led to one person withdrawing from the group. It also meant that at least some of the group members were missing from every meeting.
Reflecting on the process, one area that will require careful consideration for future iterations is the planning of the timescale for PPIE. Recruitment of PPIE representatives took several weeks, which meant that the time available for meetings became condensed. With a largely established PPIE group, this would be less of a concern for future reviews involving PPIE, but if this process were to be initiated again, more time should be allowed for recruitment and introductions to key concepts. The process would have benefited from having more time to develop and discuss ideas. A lot of complex concepts were discussed over a short time frame and, despite the group having a relatively high level of familiarity with genetics, some participants commented that they would have liked to have more time to continue discussing particularly challenging topic areas. When establishing a new PPIE group, it is important that participants are given time to share their stories and build rapport with other group members (and the team), which needs to be built into the process. The group built rapport quickly, helped by their sense of shared experiences, as most were parents to a child (or adult child) with a rare genetic condition – although, their journeys through these experiences (and the conditions their children lived with) were very different. In PPIE groups with less shared experience, early rapport-building activities and careful chairing of the group are likely to be required.
Producing the documentation for pre-reading also required time and careful consideration to pitch the information at the correct level while also presenting a broad and balanced overview of the topics. The importance of not overburdening participants also had to be taken into account. Most of the documentation provided to the group was ‘bespoke’ and summarised information from the literature to ensure it was at the right level. This was also necessary to ensure that participants were not overwhelmed, and reading could be done within the hour allowed for meeting preparation. Again, for future iterations, the importance of carefully curating the materials provided to the group should not be underestimated.
The evaluation questionnaires were not only a useful source of evaluation data on the process, but these also proved helpful to allow group members to express views they may not have had the time for, or felt comfortable to express, in meetings. The comments on the forms (which included questions on whether there was anything that surprised them, or particularly stuck in their minds following a meeting) gave an insight into how their views were developing over time.
Comments from the group on the integration of PPIE into future reviews during the whiteboard exercise included the widening of perspectives to include other stakeholders, such as more charity representation, adults with later-onset conditions and children and young adults living with rare conditions. Some also commented on the inclusion of medical professionals, ethicists and representatives from commercial entities (insurance companies and pharmaceutical companies) in debates about particular topics. It was felt that the inclusion of members of the general public, while important, could be challenging in terms of recruitment and finding people with interest in this area and that they would need more background information and training in the subject area.