The Generation Study: What are the different types of result and how are they returned? 

The Generation study involves using genome sequencing as a screening tool in newborn babies. Samples are collected shortly after birth and are used to analyse the baby’s DNA, looking for specific conditions, genes and variants within those genes.

Genomics England has developed an automated pipeline that prioritises potentially relevant genetic variants. These are manually reviewed by a clinical genomic scientist seconded from the NHS with expertise in variant interpretation. If the variants are considered suitable for reporting, the result is returned to the NHS. Most cases will have no relevant variants prioritised.

In the early stages of the study, results are expected to take a few months to be returned to families. As the study continues, this is expected to reduce to two to three weeks.

Around 99% of babies will receive a ‘no condition suspected’ result. It will be sent via letter (email or post) directly from the Generation Study to participants, as well as to their GP.

The result means that the participant is very unlikely to develop one of the conditions that has been screened for. However, because this is a screening test conducted for the purpose of research, it should not be considered a clean bill of health: babies could still develop one of the conditions (which would mean that the result would be considered a false negative); they could also develop conditions that have not been screened for. Standard-of-care referrals or genomic testing should still be arranged if indicated based on the baby’s health or family history.

The result letter clarifies the above, to ensure that participants and healthcare professionals understand fully. It also includes information about what participants can expect in the future, including how their data may be used for research and the ways in which they can withdraw from the study if they wish to.

Around 1% of participants will receive a ‘condition suspected’ result, which means that the baby has been found to have a genetic variant believed to cause one of the conditions included in the study.

• Genomics England will return this result to the NHS via regional result coordinators within the relevant NHS Genomic Medicine Service Alliance.
• The regional result coordinator will identify the appropriate NHS specialist team, who will contact the family to arrange further tests to confirm either:
  • that the suspected condition is present, in which case ongoing NHS care will begin; or
  • that the result is a false positive.
• In some cases, the diagnosis may already be known to the family, or the baby may already be in specialist care.
• The specialist team and regional 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.
• The specialist team will share the outcome of the case with Genomics England to help evaluate the test.

Genomics England has carefully selected the conditions, genes and variants included in the Generation Study in order to minimise the potential for false positives.

There are, however, numerous uncertainties that could be raised by Generation Study results (see the list below). Uncertainties are inherent in any test, but may be more significant than usual here, given the screening and research-based nature of the study.

The uncertainties around the Generation Study are:

• incorrect diagnosis (such as a false positive);
• unclear diagnosis, in which follow-up tests cannot confirm or disprove a diagnosis;
• delayed diagnosis, in which it takes several tests before the condition is confirmed;
• unclear symptoms, in which it is difficult to determine when or if the baby will develop symptoms; and
• effect on the family: because these conditions are genetic, other members of the family could be impacted by the result.

This list is explained to potential participants in study materials and consent statements, to ensure that their decision to take part in the study is an informed one.

There may be a small number of cases in which the test cannot be completed – for example, because there is a technical issue affecting how the sample is obtained, extracted or analysed. This means that the baby will not be a participant in the study, and the family will be informed by Genomics England by letter (email or post).

• Most babies (around 99%) participating in the Generation Study will receive a ‘no condition suspected’ result. Parents and the baby’s GP will receive a letter by email or post.
• A ‘no condition suspected’ result is not a clean bill of health: the baby could still develop health conditions, and the Generation Study screening should not replace standard NHS care.
• Around 1% of babies will have a suspected condition. Genomics England will work with regional result coordinators to return the result to the relevant NHS specialist team, who will communicate with the family and arrange next steps to confirm the diagnosis.
• Results can be accompanied by uncertainties about whether the diagnosis is confirmed, the symptoms that will develop and what the impact will be on family members.
• In a small number of cases, it may not be possible to complete the test. Participants will be informed if this applies to them.

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: Types of result: Implications and next steps (PDF, 12 pages)
• Genomics England: Types of result: Implications and next steps (video, 6 minutes 32 seconds)

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