| Title: |
Challenges in evaluating whole genome sequencing for newborn screening: series of systematic reviews and roadmap for evidence generation for policy advisers |
| Authors: |
Freeman, K; Taylor, D; Dinnes, J; Clark, CCA; Kander, I; Scandrett, K; Chockalingam, S; Dracup, N; Court, R; Butt, F; Visintin, C; Bonham, JR; Elliman, D; Shortland, G; Mackie, A; Miedzybrodzka, ZH; Morgan, SM; Boardman, FK; Takwoingi, Y; Shinkins, B; Clarke, A; Taylor-Phillips, S |
| Publisher Information: |
BMJ Publishing Group |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Objective: To evaluate systematic review approaches to synthesising evidence for policy advisers who are considering whether to screen newborns for hundreds of rare diseases using whole genome sequencing. Design: Series of systematic reviews and roadmap for evidence generation for policy advisers. Data sources: Medline, Embase, Science Citation Index, Cochrane Library. Methods: 200 conditions included in Genomics England's Generation Study were stratified into five groups and one condition randomly selected from each group using criteria designed to maximise variability and availability of data. 30 systematic reviews were undertaken (five conditions, six review questions) about penetrance, detection rate, accuracy, benefit of earlier treatment, and benefits and harms of screening for the five conditions (search from inception to November 2023). Results were synthesised and reviewer time recorded. Genomic studies of newborn screening cohorts that reported penetrance were systematically reviewed using a non-condition specific approach (search inception to January 2024). The conditions and genes selected for reporting by these studies were identified. ClinGen was explored for synthesising evidence. All approaches were assessed by considering review effort and level and quality of evidence. Results: The five conditions selected for systematic review were pyridoxine dependent epilepsy, heritable retinoblastoma, X linked hypophosphataemic rickets, familial haemophagocytic lymphohistiocytosis, and medium chain acyl-CoA dehydrogenase deficiency. 19 689 titles were screened and 268 papers included that addressed two of six research questions (detection rate and treatment benefit). No studies were identified for the remaining four research questions. Total reviewer time for five conditions was seven months. A team of five reviewers would take over 20 years to conduct similar reviews for 200 conditions. 10 published genomic studies of newborn screening cohorts were identified with a total of 76 268 newborns. The number of ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1136/bmjmed-2025-001726 |
| Availability: |
https://doi.org/10.1136/bmjmed-2025-001726; https://ora.ox.ac.uk/objects/uuid:3ddd0d5d-480b-40ca-aee1-3deed11b26cf |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial (CC BY-NC) |
| Accession Number: |
edsbas.DAE08A1F |
| Database: |
BASE |