Who are we?

We are a team of researchers from the Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool. We have been commissioned by the NIHR to undertake a scoping study to explore the cost-effectiveness of NGS compared with traditional sequential genetic testing for the diagnosis of learning disabilities in children. Although we intend to focus primarily on children of preschool age, we would also welcome any views you might have relating to diagnosing children and young people up to the age of 18 years. The study is due for completion in the winter of 2013.

Background to the study

Conventional genetic testing for learning disabilities has focused on sequential testing, which is often based on individual clinical characteristics. These include karyotyping, aCGH and single gene tests. Such testing can be a time-consuming process and in many cases does not provide a diagnosis. The development of NGS technologies enables sequencing to be extended to large panels of genes, providing a method for simultaneous analysis that reduces time to diagnosis and may increase diagnostic yield. These panels are made up of genes that are known to be related to specific clinical presentations. This is known as targeted exome sequencing. Analysis using NGS can also be undertaken of the whole exome/genome if desired.

Next-generation sequencing technology is developing rapidly and its use may offer advantages when diagnosing learning disabilities in children. However, although panels of genes targeted at specific clinical presentations are currently being developed for this patient group, with access to some available in the NHS, their use is not widespread. NGS technologies for whole genome and exome sequencing are currently only available for research purposes. This study explores the desirability and feasibility of employing NGS routinely (in particular in relation to looking at panels of genes) in clinical practice by the NHS, for young patients suspected of having learning disabilities. The study will also look at associated requirements for additional resources and the accompanying cost implications.

Study objectives

• Describe current pathways for this patient group that involve the use of genetic testing.
• Collect stakeholder views on the changes in service provision that would need to be put in place before NGS could be used in clinical practice.
• Describe the new systems and safeguards that would need to be put in place before NGS could be used in clinical practice.
• Explore the cost-effectiveness of NGS compared with conventional genetic testing.

Study format

The study is drawing on qualitative and quantitative material from several sources, including interviews with stakeholders from a variety of relevant backgrounds. Some of the invited interviewees have agreed to be members of our RAG; others have been suggested by the RAG members or by other people with whom we’ve already spoken. You have been recommended because of your knowledge and experience as (select as relevant):

• a paediatrician/community paediatrician
• a clinical geneticist
• a genetic counsellor
• a bioinformatician
• a staff member from a NHS genetic testing centre
• a representative of a voluntary or similar organisation.

Your contribution

We recognise that genetic testing is a rapidly changing and developing area. We also appreciate that many potential costs and benefits associated with various aspects of diagnosing learning disabilities in children are very difficult to quantify. Nevertheless, we need to identify and document as many of the potential tangible and intangible costs and benefits as possible. To assist us with this, we would like to hold a semistructured telephone interview with you to discuss your thoughts and views. We anticipate that the interview will last for about 20–30 minutes.

We would like to start the interview by (briefly) exploring your understanding, knowledge and experience of NGS as we recognise that this will vary considerably across the interviewees. During the remainder of the interview we can discuss anything that you think is relevant to our research. However, we are particularly interested in discussing the potential resource implications (e.g. workforce requirements; training requirements) for your organisation and/or profession of a move towards greater use of NGS when diagnosing learning disabilities in children. To this end, we would like to include the following broad areas during the interview (include relevant text).

Paediatrician/community paediatrician/paediatric neurologist

• (If relevant) How does the work of a paediatric neurologist differ from that of a paediatrician/community paediatrician (especially with reference to the patient group)?
• Who or what influences the decisions to use traditional methods or other approaches when seeking diagnoses in children who may have learning disabilities?
• What are their strengths and weaknesses?
• What are their resource implications?
• Who bears the associated costs?
• How closely do you work with clinical geneticists after referring a child for genetic testing?
• Have you personally used NGS for targeted exome sequencing in this patient group?
  • If so, what did you like/dislike about it? How was it funded?
  • If not, would you like to be able to use NGS?
• Do you think that NGS will be acceptable to this patient group?
• How do you see the use of NGS by the NHS changing over the next year and over the next 5 years?
• How do you think this will impact on your work, your department and your clients (e.g. with regard to extra resources and training)?

Clinical geneticist

• Who or what influences the decisions to use traditional methods or other approaches when seeking diagnoses in children who may have learning disabilities?
• What are their strengths and weaknesses?
• What are their resource implications?
• Who bears the associated costs?
• How closely do you work with the referring paediatricians (from your own and other hospitals)?
• Have you personally used NGS for targeted exome sequencing in this patient group?
  • If so, what did you like/dislike about it? How was it funded?
  • If not, would you like to be able to use NGS?
• Do you think that NGS will be acceptable to this patient group?
• How do you see the use of NGS by the NHS changing over the next year and over the next 5 years?
• How do you think this will impact on your work, your department and your clients (e.g. with regard to extra resources and training)?

Genetic counsellor

• During the interview we wish to explore:
  • the role and day-to-day work of a genetic counsellor
  • the types and places of employment of genetic counsellors
  • their required qualifications and training (and the time required for these)
  • an estimate of a ‘typical’ caseload for a genetic counsellor (specialist and/or generic)
  • your views (and/or those of your colleagues) on the acceptability of NGS to patients
  • the potential implications for genetic counsellors of an increase in the use of NGS for targeted exome sequencing when seeking a diagnosis for children who may have learning disabilities
  • how this might impact on the required numbers of genetic counsellors – in the next year and in the next 5 years
  • are there other resource-related implications (e.g. for the NHS)?
  • what other (broad) changes and developments will need to occur to enable NGS to be used more widely for the diagnosis of learning disabilities in children?

Bioinformatician

• During the interview we wish to explore:
  • the role and day-to-day work of bioinformaticians
  • the types and places of employment of bioinformaticians
  • their required qualifications and training (and the time required for these)
  • typical arrangements for supervision and audit of their work
  • the potential implications for bioinformaticians of an increase in the use of NGS when seeking a diagnosis for children who may have learning disabilities
  • how this might impact on the required numbers of bioinformaticians – in the next year and in the next 5 years
  • are there other resource-related implications (e.g. for the NHS)?
  • what other (broad) changes and developments will need to occur (in the NHS and/or in the private sector) to enable NGS to be used more widely for the diagnosis of learning disabilities in children?

Staff member from a NHS genetic testing centre

• During the interview we wish to explore:
  • the current and potential roles of NHS genetic testing centres in the diagnosis of learning disabilities in children
  • the likely involvement of NHS genetic testing centres in the use of NGS in this patient group over the next year and the next 5 years
  • what developments would be needed at NHS genetic testing centres to implement any changes?
  • what would be their likely resource implications?

Representative of a voluntary organisation or other body

• During the interview we wish to explore:
  • the importance for families of having a diagnosis for a child with learning disabilities
  • how might having (or not having) a diagnosis for such a child affect decisions about their health care, social care and education?
  • how might other family members be affected by having (or not having) a diagnosis for such a child?
  • do you think that NGS will be acceptable to this patient group?
  • how might potential developments in genetic testing (over the next year and over the next 5 years) affect the lives of the children and/or their families (positively and/or negatively)?
  • what are the potential resource implications of such developments (for your organisation and for other voluntary organisations and support groups)?

If we have not already covered these, we would like to conclude your interview with a brief discussion of what you think are the main strengths and weaknesses of traditional approaches and NGS, including their implications for the patient group. Finally, if you know of any colleagues with expertise or experience that will inform this project then please provide us with their contact details.

Potential benefits of the study

We anticipate that all the professional groups contributing to the scoping study will benefit from a greater knowledge and understanding of the strengths and weaknesses of NGS compared with traditional approaches for the diagnosis of learning disabilities in children. The study findings will be published as a report by the NIHR and will be available from their website. In addition, everyone participating in the face-to-face and telephone interviews will be invited to a dissemination event. This is likely to be held in Liverpool (at the University) once the project report has been finalised (i.e. early 2014).

For further information please contact: xxx (ku.ca.looprevil@xxx or 0151 xxx xxxx).