Leading Edge 2022 Issue 2

12 LEADING EDGE - 2022-2 Alpha Laboratories recently held a FIT user group meeting that was attended by some of the leading laboratories who utilise the HM-JACKarc technology for their faecal immunochemical testing service. Key speakers discussed their challenges and contributions towards standardisation and quality in FIT testing. Symptomatic FIT and the Role of the Laboratory: Overview, Lessons Learned and Future Development David Evans, Symptomatic FIT Co-Ordinator, Public Health Wales David presented a simplified patient referral pathway for both primary and secondary care in Public Health Wales (PHW). This comprises of an online interface that allows clinicians to submit electronic FIT referrals. These requests are downloaded from the online interface by the PHW laboratory and FIT-KITs are sent directly to the patients address for collecting their sample at home. The kits include the EXTEL HEMO AUTO MC Collection Picker, with complete instructions for collecting and returning the sample. Within a turnaround time of 9 days (from referral submission to result authorisation), samples are returned to the laboratory, faecal haemoglobin (f-Hb) is quantified and results are easily transferred to an online interface (LIMS) for access by GPs and referring consultants. PHW currently receives 4500-5000 referrals per month and reports an average return rate of 82%. David also shared a projected increase in demand for symptomatic referrals, particularly from primary care. Secondary care referrals remain consistent (See Figure 1). David further shared that with the use of the HM-JACKarc system, PHW are observing a 19% positivity rate across health boards using their service (% samples > 10µg/g of Hb), although a higher variation can be observed in health boards with a lower throughput. The major challenges faced by PHW are the number of non-responders, a lack of administrative support to track each patient and prompt non-responders and the lack of understanding between symptomatic FIT and bowel cancer screening FIT. Further developments will implement electronic requesting and focus on working closely with stakeolders to improve non-responder rate. FIT Quality Assurance Carolyn Piggot, FIBMS, Research Scientist, Bowel Cancer Screening Programme, Southern Hub, Guildford Carolyn Piggott presented on the factors that contribute towards the pre-analytical and laboratory challenges faced in FIT testing. The major contributors are the differences in faecal samples, inconsistent sampling by participants and haemoglobin (Hb) stability in faeces. In addition to sample variability, there is no FIT assay standardisation. Different reagents are used between each manufacturer and there is no primary reference materials of methodologies. The lack of standardisation or harmonisation of FIT means that variations are observed in f-Hb results generated on different systems. Carolyn mentioned a range of approaches to tackle these challenges. One is manufacturers‘ development of new buffers, focused on improved sample stability. Projects are also being undertaken at BCSP Guildford which include evaluation of the available EQA (Ref.1), third party internal QC (Ref.2) and the effect of Hb-variants (Ref.3). In addition, they are working in conjunction with the IFCC FIT Working Group established in 2017 to formally address the challenges (representatives from other manufacturers, clinical scientists, and representatives from EQA companies) according to the references below (Ref.4): Terms of Reference • To attempt to standardise analysis of haemoglobin in faecal samples by immunochemistry (FIT) • To identify all sources of pre-analytical variation and standardise if possible • To establish external quality assurance and third party internal quality control programmes • To determine impact of assay interference of Hb variants and other factors So far, work has been completed to establish the current status of 4 automated FIT systems (Ref.5): HM-JACKarc (Minaris Medical Co. Ltd, Japan): OC-Sensor PLEDIA (Eiken Chemical Co. Ltd, Japan); SENTiFIT 270 (Sentinel Diagnostics, Italy), NS-Prime (Alfresa Pharma, Japan); data show that all analysers met manufacturers’ claims. Additionally, EQA programmes investigated types and imprecision of EQAS available worldwide. 13 manufacturers of EQA were identified and 11 agreed to take part, to either provide: faecal-like material loaded by participants (UK NEQAS and HECTEF, Japan), faecal-like material loaded by EQA provider (WEQAS and CEQAL, Canada), or aqueous material loaded directly onto the analysers in cups (CRB, Italy, ESFEQA, Germany, Labquality, Finland, SEKK, Czech Republic, SEQC, Spain, SKML, Netherlands). Results showed that faecal-like matrices have larger coefficient of variant (CVs), and liquid materials have smaller CVs. Carolyn also reported on the evaluation of QC material from each FIT manufacturer, measured on the other three analysers, and the CVs were overall <9% and mostly <5%. Considering there were no third-party QCs available (in 2019), QC material available from the 4 FIT manufacturers could be used Working Towards Quality Standardisation for Faecal Immunochemical Testing (FIT)