Dr Rachel Carling  

Rachel Carling graduated with a first class honours degree in Chemistry from Manchester University in 1996. She then gained a PhD in Analytical Chemistry before moving to Leeds and training as a Clinical Biochemist. She chose to specialise in metabolic biochemistry because of her interest in analytical techniques and became one of eight Higher Specialist Trainees in Metabolic Biochemistry, obtaining FRCPath in 2007. Rachel is now a Consultant Clinical Scientist at Synnovis, Guy’s & St Thomas’ Hospital where she is Director of South East Thames Regional Newborn Screening Laboratory, Scientific Head of Service and Clinical Lead for Biochemical Sciences.  She is also Chair of the UK Metabolic Biochemistry Network and a Screening Professional Clinical Advisor (ANNB laboratory) to NHSE.

Her main areas of interest is inherited metabolic disease with a particular focus on the application of tandem mass spectrometry to the measurement of small molecules. She is passionate about science, an advocate of A3 thinking and committed to service improvement.  

From Laboratory Developed Tests to a Single Commercial Assay: National Experience of Harmonising Screening for Inherited Metabolic Diseases

The introduction of screening for Hereditary Tyrosinemia Type 1 (HT1) in England coincided with a national decision to implement a single commercial tandem mass spectrometry reagent kit across all newborn screening laboratories. This represented a major analytical and operational challenge: achieving harmonised performance across 13 laboratories using 26 tandem mass spectrometers from multiple manufacturers, while safeguarding screening sensitivity and specificity.

A structured national harmonisation strategy was implemented following assay installation and local verification. Instrument specific relative response factors were applied in line with manufacturer guidance for nine analytes, including succinylacetone. Succinylacetone proved the most challenging marker, displaying significant variability between instruments at lower concentrations. 

Post harmonisation population distributions from 24,000 newborns were reviewed centrally and compared with historic laboratory developed test data from 140,000 samples using centile analysis, MAD and rain shower plots. Inter laboratory variation improved for all analytes, demonstrating improved harmonisation. However, this was achieved by application of instrument-specific correction factors to all analytes, the magnitude of which were significant, indicating a lack of standardization.

This work demonstrates that while a single commercial kit can substantially improve harmonisation at national scale, true standardisation remains difficult to achieve. In the absence of matrix matched certified reference materials for these analytes, sustained harmonisation will depend on robust internal quality control, regular monitoring using third party materials, and strong collaborative governance across screening laboratories.