Perceptions of the CF Screening Protocol Incorporating NGS

Exploring Perceptions on the Proposed Cystic Fibrosis Screening Protocol Incorporating Next Generation Sequencing

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 was 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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

People with experience of CF, CFSPID or carrier status and health professionals with experience of caring for them.

Description

Inclusion Criteria:

1. Adults aged over 18 years of age who:

   (i) Were diagnosed with CF in childhood (ii) Were diagnosed with CF as adults (including those who would have been identified as CFSPID if NBS had been available and reporting it) (iii) Are carriers of CF (including parents/relatives of children/adults with CF and adults identified via other routes e.g. private testing)

2. Parents (aged over 18 years) of children identified through NBS who:

   (iv) Have CF (v) Are carriers of CF (vi) Have a CFSPID designation (vii) Have received a false positive NBS result for CF (viii) Have received a false negative NBS result for CF

3. Children aged over 10 years of age* who:

   (ix) Have CF (x) Have a CFSPID designation (xi) Are carriers of CF and have been informed of their carrier status

   *Ten years of age has been chosen for both pragmatic reasons and because this represents the age at which children will begin preparing for transition to adult services and therefore a period of increased independence and/or preparing for specialist review

4. Professionals involved in processing and/or communicating positive NBS results for CF to families or supporting families in health, community or education settings e.g. doctors, nurses, geneticists, genetic counsellors, midwives, social workers, dieticians, physiotherapists, teachers, university lecturers, charities.

Exclusion Criteria:

Exclusion criteria for those affected by CF:

1. Adults or children with non CF related co-morbidities that are likely to influence their perception of the proposed CF screening protocol incorporating NGS
2. Parents whose child has died prior to being approached to be involved in the study
3. Adults or children unable to understand the PIS and give informed consent/assent respectively
4. Adults or children whose recruitment is contraindicated on psychosocial or medical grounds (identified by their health visitor or specialist team).

Exclusion criteria for professionals:

Those not involved in processing, communicating positive NBS results for CF to families or supporting families in health, community or education settings.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
People with experience of cystic fibrosis; Adults or children with experience of CF.
Health professionals; Health professionals with experience of caring for people with experience of CF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Focus groups/interviews/questionnaires exploring stakeholder views of the proposed CF screening protocol incorporating NGS.	Focus groups/interviews/questionnaires exploring stakeholder views, experiences and conceptualized harms/benefits in relation to the proposed CF screening protocol incorporating NGS	February 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Focus groups/interviews/questionnaires exploring stakeholder views on equivocal, carrier, false positives/negatives results, late onset/uncertain conditions	Focus groups/interviews/questionnaires exploring stakeholder views on equivocal, carrier, false positives/negatives results, late onset/uncertain conditions identified early in life (infertility, potential CF), missed CF diagnoses, as well as the way these outcomes are prioritised and ordered when considering NGS for CF NBS	February 2023
Q sorts used to develop data and materials FMCH and UK NSC can use to engage stakeholders	Q sorts used to develop data and materials FMCH and UK NSC can use to engage stakeholders more widely with discussions about a) the proposed protocol, and b) wider use of genomic testing in NBS	February 2023
Surveys to explore principles of engagement for stakeholders	Surveys to explore principles of engagement for this population, building on the 'golden rules' but with context specific guidance under each that can be used in future commissioning	February 2023

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Barts & The London NHS Trust; University of Warwick; Coventry University; Cystic Fibrosis Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2022
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: CF NGS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data are available on request from the corresponding author. The data are not publicly available due to ethical constraints

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No