The Generation Study: Communicating a ‘condition suspected’ result

Around 1% of newborn babies in the Generation Study will be suspected as having a genetic variant or variants believed to cause one of the conditions included in the study. When this happens, the process below will be followed.

• Genomics England will create a result referral pack, which includes the genomic research report, key information and resources.
• They will return this pack to the regional result coordinator in the relevant NHS Genomic Medicine Service Alliance.
• The regional result coordinator maintains a list of relevant NHS specialists within their region for each of the conditions included in the study. They will share the result referral pack with the appropriate specialist team.
• The regional result coordinator will support the specialist team in finding out whether the diagnosis is already known to the family (or even whether the baby is already receiving care for the suspected condition). If the condition may already have been detected by the NHS newborn blood spot test, they will contact the relevant NHS screening laboratory to check the result.
• The NHS specialist team will plan and instigate next steps for testing and care, based on the clinical urgency of the suspected condition. They may need to collaborate with other clinical and laboratory teams.
• The NHS specialist team will contact the family, usually by phone initially, to communicate the ‘condition suspected’ result. They will discuss next steps, including further tests or referrals, and will communicate the implications, uncertainties and limitations of any further tests.
• The specialist team and the regional result coordinator will help families access support, including study-funded genetic counselling and links to patient organisations. Participants are also offered reimbursement for travel to the initial NHS consultation after a ‘condition suspected’ result is identified. Such support may be offered when the result is first communicated, at subsequent appointments or after a diagnosis is confirmed (or after the result is determined to be a false positive).
• The specialist team will be asked to share important outcome information about the case with Genomics England to help with the test evaluation.
• Upon being informed of the outcome, Genomics England will send the participants a letter about what to expect if they remain part of the study, including how their data may be used for research and how they might withdraw if they wish to.

For more information about the types of result that might be returned in the Generation Study, please see The Generation Study: What are the different types of result and how are they returned?

The result referral pack is comprised of the following, all of which have been developed and tested with a working group that includes healthcare professionals and individuals with experience of rare conditions or newborn screening results.

• Initial ‘condition suspected’ email. This shares the result with the relevant NHS specialist.
• Genomic research report. This outlines the genetic variants that have been found that suggest that the newborn is suspected to have one of the conditions included in the study. The report states which condition is suspected, the variants found and how they were classified, as well as the test methodology. All variants are manually reviewed by a clinical genomic scientist with expertise in variant interpretation who has been seconded from the NHS to Genomics England. Importantly, the report highlights that the result is research-based, and that confirmatory testing is needed.
• Confirmatory test pathway. Each condition with a unique confirmatory test and intervention will have a defined pathway for the specialist team receiving the result. Pathways aim to provide high-level, condition-specific guidance on the urgency of the initial review, confirmatory diagnostic and genomic tests, management and onward support.
• Condition information sheet. Each condition will have an information sheet aimed at parents in the period immediately after a ‘condition suspected’ result has been returned and before a diagnosis is confirmed. Information sheets provide high-level information about the condition suspected, next steps and where to find more information and support, including links to relevant patient organisations.
• Patient contact information. This includes identifiable information about the newborn baby and their mother (who gave consent for participation in the study). It includes information taken when consent was collected and from NHS Spine, to support the regional result coordinator and specialist clinician in locating and contacting the family with the result. It will highlight whether an interpreter is needed.
• Result call guideline. This is a just-in-time resource for the specialist clinician contacting the family to help structure the initial contact. This may be an unexpected and worrying experience for parents, and may also be different to what many specialists are used to (because the result is not a diagnosis and the baby may not have any symptoms). The guideline includes key insights about specific communication challenges that arise from giving a genomic result in a screening context.
• Result follow-up email to parent. This is a template that can be used by the specialist clinician after they have contacted the family to confirm next steps. They will need to input details to tailor it as required, including details of an appointment for further testing or particular symptoms that parents should be aware of.
• Results pack checklist. This summarises the key steps and resources in the result referral pack.

When NHS specialists are contacted with a ‘condition suspected’ result, they are asked to complete a short form to share diagnostic outcomes with the Generation Study team. The information contained within this form is a vital part of understanding how accurate and useful the study has been for healthcare professionals and participants. In order to gather evidence that can inform future decisions about the use of genome sequencing in newborns, it is important to be able to evaluate true positives, false positives and additional clinical findings related to the genetic conditions that have been identified in the study. Regional result coordinators will support NHS specialists in making sure the form is completed.

• Around 1% of babies will be suspected as having a genetic variant or variants believed to cause one of the conditions included in the study. It is important to remember that this is not a diagnosis, and that further testing is needed.
• Genomics England will work with regional result coordinators to return the research result to the relevant NHS specialist team, who will communicate it to the family and arrange next steps to confirm the diagnosis and provide support.
• The result referral pack includes key information to support specialist teams in contacting families and communicating the result.
• Specialist teams are also asked to complete a brief diagnostic outcome form to share information from further testing, which will help the team evaluate the study.

For clinicians

• Genomics Education Programme: CPI: Generation Study: Recruit, enrol and sample
• Genomics Education Programme: CPI: Generation Study: Return results and further care
• Genomics Education Programme: CPI: Generation Study: Sample, sequence and interpret
• Genomics England: Generation Study: The result referral pack (video, 5 minutes 10 seconds)
• Genomics England: The result referral pack (PDF, 12 pages)

For clinicians returning results, there are numerous education and training resources. Modules include:

• ‘The process of returning a result’;
• ‘Making the phone call’; and
• ‘Possible scenarios’.

Please note that some of these resources are hosted on the Generation Study workspace on the NHS Futures platform. If you have not already had an invitation to join, please contact the Genomics England service desk: generationstudy@genomicsengland.co.uk.

Content may evolve over time. Should you have any issues accessing the content, please contact the service desk.

For patients

• Genomics England: The Generation Study
• Genomics England: The Generation Study Participant Information Sheet
• Genomics England: The Generation Study translated participant information