title: A scoping study to explore the cost-effectiveness of next-generation sequencing compared with traditional genetic testing for the diagnosis of learning disabilities in children.
abstract: BACKGROUND
  Learning disability (LD) is a serious and lifelong condition characterised by the impairment of cognitive and adaptive skills. Some cases of LD with unidentified causes may be linked to genetic factors. Next-generation sequencing (NGS) techniques are new approaches to genetic testing that are expected to increase diagnostic yield.
  
  
  OBJECTIVE
  This scoping study focused on the diagnosis of LD in children and the objectives were to describe current pathways 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; and explore the cost-effectiveness of using NGS compared with conventional genetic testing.
  
  
  METHODS
  A research advisory group was established. This group provided ongoing support by e-mail and telephone through the lifetime of the study and also contributed face-to-face through a workshop. A detailed review of published studies and reports was undertaken. In addition, information was collected through 33 semistructured interviews with key stakeholders.
  
  
  RESULTS
  NGS techniques consist of targeted gene sequencing, whole-exome sequencing (WES) and whole-genome sequencing (WGS). Targeted gene panels, which are the least complex, are in their infancy in clinical settings. Some interviewees thought that during the next 3-5 years targeted gene panels would be superseded by WES. If NGS technologies were to be fully introduced into clinical practice in the future a number of factors would need to be overcome. The main resource-related issues pertaining to service provision are the need for additional computing capacity, more bioinformaticians, more genetic counsellors and also genetics-related training for the public and a wide range of staff. It is also considered that, as the number of children undergoing genetic testing increases, there will be an increase in demand for information and support for families. The main issues relating to systems and safeguards are giving informed consent, sharing unanticipated findings, developing ethical and other frameworks, equity of access, data protection, data storage and data sharing. There is little published evidence on the cost-effectiveness of NGS technologies. The major barriers to determining cost-effectiveness are the uncertainty around diagnostic yield, the heterogeneity of diagnostic pathways and the lack of information on the impact of a diagnosis on health care, social care, educational support needs and the wider family. Furthermore, as NGS techniques are currently being used only in research, costs and benefits to the NHS are unclear.
  
  
  CONCLUSIONS
  NGS technologies are at an early stage of development and it is too soon to say whether they can offer value for money to the NHS as part of the LD diagnostic process. Substantial organisational changes, as well as new systems and safeguards, would be required if NGS technologies were to be introduced into NHS clinical practice. Considerable further research is required to establish whether using NGS technologies to diagnose learning disabilities is clinically effective and cost-effective.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Liverpool Reviews and Implementation Group (LRiG), University of Liverpool, Liverpool, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Beale
authors.affiliation: Mill Mount Consulting, Easingwold, York, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Sanderson
authors.affiliation: Liverpool Reviews and Implementation Group (LRiG), University of Liverpool, Liverpool, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Sanniti
authors.affiliation: Liverpool Reviews and Implementation Group (LRiG), University of Liverpool, Liverpool, UK.
authors.forename: Yenal
authors.initials: Y
authors.lastname: Dundar
authors.affiliation: Liverpool Reviews and Implementation Group (LRiG), University of Liverpool, Liverpool, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Boland
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D005260:Female; D005820:Genetic Testing / Q000191:economics* / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007859:Learning Disabilities / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D010290:Parents / Q000523:psychology; D013222:State Medicine; D055815:Young Adult