Perceptions of the CF screening protocol incorporating NGS
Research type
Research Study
Full title
Exploring perceptions of the proposed cystic fibrosis screening protocol incorporating next generation sequencing
IRAS ID
307623
Contact name
Jane Chudleigh
Contact email
Sponsor organisation
King's College London
Clinicaltrials.gov Identifier
Pending, ISRCTN
Duration of Study in the UK
1 years, 2 months, 28 days
Research summary
Research Summary:
Newborn bloodspot screening (from now on referred to as screening) for cystic fibrosis (CF) became part of the national screening programme in 2007. Screening for CF is also well established internationally. The current process works well but has some disadvantages: carrier reporting - which is not the intention of CF screening in the UK (~200 pa); need for repeat samples which can be costly and contribute to parental worry (~300 pa.); mutation panels not fully reflecting the ethnic diversity of the birth population; identification of children designated as CF screen positive, inconclusive diagnosis (CFSPID) which can cause uncertainty (~20-30 pa).A trial of NGS in one centre in the UK, for one year found that it was technically feasible at reasonable cost and with an acceptable turn around time. In addition, the trial determined that using NGS could mitigate against some of the disadvantages described above.
The purpose of this piece of work is to:
1. Gather, compare and analyse the views of a range of stakeholders on the proposed CF screening protocol incorporating NGS.
2. Use the outcomes to inform discussions and decisions by the fetal, maternal and child health (FMCH) group and UK National Screening Committee (NSC) about the proposed protocol
3. Consider what generalisable information on the views of stakeholders on newborn screening could be generated from this exercise to inform other FMCH and UK NSC discussions
4. Evaluate and learn from the exercise to inform future stakeholder engagement activities by the UK NSC and screening programmes.Summary of Research:
Changes to the way in which newborns are screened for cystic fibrosis (CF) in the UK have been proposed. These changes include the use of next generation sequencing, that, depending on how the test is used, will either increase its sensitivity (to identify more cases of CF but identify more newborns with the uncertain cystic fibrosis screen positive, inconclusive diagnosis (CFSPID) designation) or increase its specificity (reducing the identification of CFSPID designations, but increasing the number of missed diagnoses of true CF).The aim of this project was to gather, analyse and compare the views of a range of stakeholders linked to CF on these proposed changes to the CF screening protocol.
The project commenced December 2021 and was completed in February 2023.
The project used a range of methods, including a questionnaire, focus groups, interviews and deliberative workshops using Q methodology and a willingness to pay exercise. The scope, structure and data collection tools for the project were developed in collaboration with patient representatives through involvement activities at the outset and at key stages of project progress.
In Work Package (WP) 1, eight focus groups were conducted involving 35 adults with personal experience of CF, CFSPID or CF carrier status, and six interviews with children with CF. An online questionnaire was administered to health care professionals involved (in some capacity) in CF care, receiving a total of 108 usable responses (47 UK, 27 Europe/RoW, 34 US). The findings of the interviews, focus groups and questionnaire were used to develop the materials for the deliberative workshops in WP2. Four deliberative workshops were held with adults (n=28) with personal experience of CF, CFSPID or carrier status and health professionals (n=9) with experience of CF care, to further explore views and experiences and inform recommendations.
Across these methods, the results indicated that most participants had a strong preference for the sensitive approach to NGS. This was due to the perceived importance of identifying as many children as possible with CF as early as possible to enable them to access appropriate treatment, and better health outcomes for the child. In addition, identifying more children with CFSPID was considered potentially beneficial to avoid a diagnostic odyssey and facilitate early access to treatment should the child become symptomatic. Participants also suggested that identifying more children with CFSPID would support a better understanding of the implications of the designation amongst health care professionals and contribute to the development of an evidence base to support its management. Good quality communication with parents and the provision of relevant information were seen as pivotal to realising these benefits whilst minimising harms.
While it was acknowledged that identifying more cases of CFSPID might have implications for NHS resources, most participants thought this would be mitigated by (i) the additional scientific knowledge gained to inform the management of these children and potentially reduce overmedicalisation (ii) reduction in resources associated with a diagnostic odyssey in those cases where a child with CFSPID child converts to a CF diagnosis or develops a CFTR related disorder (in terms of the various appointments, referrals, tests, hospital admissions etc.,) (iii) reduction in clinical and psychological impacts on the child and family of a missed diagnosis of CF.Key messages associated with this preference were as follows:
1. The sensitive approach to next generation sequencing for CF screening should be adopted.
2. Information provision at the time of screening should include an explanation of CFSPID as a possible outcome.
3. Specific support groups for parents of children with a CFSPID designation are needed.
4. A health economic analysis of the actual costs associated with managing a CFSPID designation as well as identifying a missed case of CF or CFSPID should be conducted.
5. Research should be conducted to inform definitive written guidelines for health professionals regarding the clinical management of children with a CFSPID designation to avoid over-medicalisation.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
22/NE/0024
Date of REC Opinion
19 Jan 2022
REC opinion
Further Information Favourable Opinion