Barrett’s oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux

Abstract

BackgroundEarly detection of oesophageal cancer improves outcomes; however, the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett’s oesophagus (BE) is not clear. The Cytosponge, a novel non-endoscopic sponge device, combined with the biomarker Trefoil Factor 3 (TFF3) has been tested in four clinical studies. It was found to be safe, accurate and acceptable to patients.The aim of the BEST3 trial is to evaluate if the offer of a Cytosponge-TFF3 test in primary care for patients on long term acid suppressants leads to an increase in the number of patients diagnosed with BE.MethodsThe BEST3 trial is a pragmatic multi-site cluster-randomised controlled trial set in primary care in England. Approximately 120 practices will be randomised 1:1 to either the intervention arm, invitation to a Cytosponge-TFF3 test, or the control arm usual care. Inclusion criteria are men and women aged 50 or over with records of at least 6 months of prescriptions for acid-suppressants in the last year. Patients in the intervention arm will receive an invitation to have a Cytosponge-TFF3 test in their general practice. Patients with a positive TFF3 test will receive an invitation for an upper gastro-intestinal endoscopy at their local hospital-based endoscopy clinic to test for BE.The primary objective is to compare histologically confirmed BE diagnosis between the intervention and control arms to determine whether the offer of the Cytosponge-TFF3 test in primary care results in an increase in BE diagnosis within 12 months of study entry.DiscussionThe BEST3 trial is a well-powered pragmatic trial testing the use of the Cytosponge-TFF3 test in the same population that we envisage it being used in clinical practice. The data generated from this trial will enable NICE and other clinical bodies to decide whether this test is suitable for routine clinical use.Trial registrationThis trial was prospectively registered with the ISRCTN Registry on 19/01/2017, trial number ISRCTN68382401.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4664-3) contains supplementary material, which is available to authorized users.

Development and validation of a risk prediction model to diagnose Barrett's oesophagus (MARK-BE): a case-control machine learning approach

“…To this end, we propose that our algorithm should be applied to the data generated from the BEST3 study, which is a pragmatic, multisite, cluster-randomised controlled trial set in primary care centres in England, UK, where the prevalence of Barrett's oesophagus is representative of the general UK population and in which the same questions have been asked as in BEST2 and BOOST. 52 We are also undertaking another prospective study (ISRCTN 11921553) to test this hypothesis independently in a second population that more closely aligns with the general population prevalence of the disease.…”

Role of TFF3 as an adjunct in the diagnosis of Barrett's esophagus using a minimally invasive esophageal sampling device—The CytospongeTM

“…37 In this trial the use of high and low confidence scores for both negative and positive results are being evaluated. 37 In this trial the use of high and low confidence scores for both negative and positive results are being evaluated.…”

“…Further validation of the Cytosponge TM -TFF3 test is now underway in a multicenter cluster-randomized controlled trial, BEST3, which aims to recruit 9000 participants over a 3 year period. 37 In this trial the use of high and low confidence scores for both negative and positive results are being evaluated. If no glandular cells are identified, suggesting that the device may not have reached the stomach, the case is reported as "negative with low confidence" and the patient is invited for a repeat test.…”

Early detection and therapeutics

“…Taken together, Cytosponge coupled with TFF-3 is promising for a wide-ranged screening; however, it still requires randomised trial data to fully evaluate its diagnostic yield, cost-effectiveness and safety profile. This is currently underway in the BEST3 trial (ISRCTN68382401), which is a randomised trial in 13 000 individuals in multiple UK primary care sites (funded by Cancer Research UK) (Offman et al, 2018).…”