Table 7 Amendments to the study protocol post 6 months milestone review

Cytosponge appointment uptake 27%: Substantial impact on sample size as number of practices would have to be increased to ~ 200

1) Sample size amended

- Using uptake = 27%

- including patients with false negative Cytosponge test diagnosed with BE during 12-month follow-up: (1–0.85)*0.6%

2) Additional individual randomisation arm added to reduce the sample size

- Individual randomisation sample size (without adjusting for cluster randomisation): 6764

- Variance inflation factor (VIF) for confirmed and projected sample sizes are 3.72 and 4.5, respectively. 1 individually randomised participant would therefore be equivalent to 3.72 or 4.5 cluster randomised participants

- Practices already commenced set up on the cluster randomisation design allowed to continue to randomise in a cluster fashion

- Sample size will be adjusted depending on number of patients in cluster randomised group

Due to small number of smaller practices, stratification by both area and practice size has resulted in imbalances in arm allocations for some areas

Stratification by practice size will not be taken into account during randomisation but in the analysis instead

- To simplify randomisation and avoid any further imbalances for remaining cluster randomisation practices

- Analysis: the primary analysis will be a stratified test of proportions taking into account the variation inflation within each stratum.