Quantitative faecal immunochemical tests to guide colorectal cancer pathway referral in primary care. A systematic review, meta-analysis and cost-effectiveness analysis.

Background: Faecal immunochemical tests may be better than symptoms alone at identifying which patients who present to primary care with symptoms are at high risk of colorectal cancer and should have a colonoscopy. This could reduce waiting lists and patient anxiety/discomfort and enable earlier treatment of colorectal cancer. The threshold used will affect how well faecal immunochemical tests work, with a higher threshold resulting in fewer referrals but a greater chance of missing disease.

Objective: What is the most clinically effective and cost-effective way to use faecal immunochemical tests to reduce the number of people without significant bowel pathology who are referred to the suspected cancer pathway for colorectal cancer, taking into consideration potential colonoscopy capacity constraints for urgent and non-urgent referrals? Tests were HM-JACKarc, OC-Sensor, FOB Gold, NS-Prime, QuikRead go, IDK TurbiFIT, IDK Hb, IDK Hb/Hp complex and IDKHb+Hb/Hp ELISAs.

Design: Systematic review, meta-analysis and cost-effectiveness analyses were conducted.

Review methods: Searches across four databases and six registries were conducted (December 2022). Diagnostic accuracy studies conducted in patients presenting to or referred from primary care with symptoms suggestive of colorectal cancer using any reference standard were included. Risk of bias was assessed with quality assessment of diagnostic test accuracy studies version 2. For each test, sensitivity and specificity were pooled at all reported thresholds and summary estimates were provided at all possible thresholds within the observed range. Comparative accuracy between tests was considered. Other outcomes, for example test uptake, failure and patient acceptability, were also extracted.

Cost-effectiveness analysis methods: A mathematical model was developed to compare three different diagnostic strategies that used quantitative faecal immunochemical tests in primary care patients with symptoms of colorectal cancer to determine subsequent management pathways. The model assessed the health outcomes and costs associated with each strategy over a lifetime horizon from the perspective of the United Kingdom National Health Service and Personal Social Services, using evidence from published literature and other sources.

Results: Syntheses of sensitivity and specificity were conducted for HM-JACKarc (n = 16 studies), OC-Sensor (n = 11 studies) and FOB Gold (n = 3 studies). No synthesis was conducted for QuikRead go, NS-Prime IDK Hb or IDK Hb/Hp as there was only one study for each. No eligible studies were found for IDK Hb+Hb/Hp or for IDK TurbiFIT. Other outcomes (e.g. patient acceptability) were also synthesised. Model results suggest that faecal immunochemical tests generate a positive incremental net monetary benefit compared with current care, typically in the range of £200-350 per patient, regardless of the threshold used, for the majority of faecal immunochemical tests strategies assessed. These conclusions were robust to the sensitivity analyses undertaken.

Conclusions: For all faecal immunochemical test brands, there are strategies at which the incremental net monetary benefit is positive compared with current care. The exact brand and threshold(s) that generate the greatest incremental net monetary benefit could not be robustly determined due to the similarity of incremental net monetary benefit values, parameter uncertainty and the possibility of omissions from the model structure.

Future work: More data are needed on comparative diagnostic test accuracy and whether different thresholds should be used in some patients (e.g. anaemic, male/female, younger/older).

Study registration: This study is registered as PROSPERO CRD42022383580.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135637) and is published in full in Health Technology Assessment; Vol. 29, No. 46. See the NIHR Funding and Awards website for further award information.