Factors influencing participation in randomised clinical trials among patients with Barrett’s early neoplasia: A multi-centre interview study

Objectives Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett’s Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett’s neoplasia. This paper aims to identify factors influencing patients’ participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy. Design A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes. Setting Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted. Participants We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined. Results Four themes were identified centred around interviewees’ decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant–recruiter relationship; (2) participants’ views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants’ perceptions of surgical risks versus less invasive treatments. Conclusion We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett’s-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials.</p

Spatio-temporal Classification for Polyp Diagnosis - supplementary material.mp4

Visual examples of the type of video clips used in the paper called "Spatio-temporal Classification for Polyp Diagnosis". These are short videos of polyps to be classified as adenomas or non-adenomas

Study CONSORT diagram detailing the flow of control and Barrett's esophagus patients (cases) through the study.

<p>Patients who were unable to swallow the Cytosponge or whose Cytosponge sample failed processing were excluded from the study. Exact numbers of control and BE patients who successfully completed the study are noted.</p

Modeling of Cytosponge-TFF3 testing and risk stratification in the primary care population with reflux symptoms.

<p>Extrapolation of findings to a hypothetical population of 10,000 individuals with reflux symptoms using a sensitivity and specificity of 79.9% and 92.4%, respectively, for the TFF3 screen, and a sensitivity and specificity of 86% (95% CI of 65%–96%) and 100% (95% CI of 94.6%–100%), respectively, for <i>TP53</i> mutation screening for detection of HGD. The assumed prevalence of BE was 3%. In patients found to be high risk, endoscopy within 6–8 wk would be recommended. For low-risk patients, a repeat Cytosponge-TFF3 test would be performed at an interval of several years (exact timing to be determined) in case they had become TP53 positive over this time period. In the TFF3-negative arm, the repeat Cytosponge testing might not be necessary. If it took place, repeat testing would be recommended within 6 to 8 wk of the delivery of the TFF3-negative results.</p

Sensitivity of the Cytosponge-TFF3 in different groups of patients (full dataset in S2 and S3 Tables).

<p>C, Circumferential length; IMC, intramucosal carcinoma; LGD, low grade dysplasia; M, maximal length; NDBE, non-dysplastic BE.</p><p>Sensitivity of the Cytosponge-TFF3 in different groups of patients (full dataset in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001780#pmed.1001780.s005" target="_blank">S2</a> and <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001780#pmed.1001780.s006" target="_blank">S3</a> Tables).</p

Clinical covariates have no impact on sensitivity and specificity of the test.

<p>Clinical covariates have no impact on sensitivity and specificity of the test.</p

TFF3 immunohistochemical staining of Cytosponge samples.

<p>TFF3 staining was performed on all Cytosponge samples to test the sensitivity and specificity of the Cytosponge-TFF3 test for diagnosing BE. TFF3 was scored in a binary fashion, with samples with one or more TFF3-positive goblet cells being classed as positive. Shown are immunohistochemical images illustrating examples of TFF3-negative and-positive staining at low magnification (100×) and high magnification (400×).</p

Demographics of the BEST2 Study patient cohorts.

<p>^aBE defined as endoscopically visible columnar-lined esophagus that measured at least 1 cm circumferentially or at least 3 cm in non-circumferential tongues (Prague classification ≥C1 or ≥M3).</p><p>^bSex ratio rounded to the nearest tenth.</p><p>n/a, not applicable.</p><p>Demographics of the BEST2 Study patient cohorts.</p

Acceptability of endoscopy and the Cytosponge test.

<p>Patients were asked to rate the procedures using a visual analogue acceptability scale after swallowing the Cytosponge and after endoscopy. The colors representing the different acceptability scores are shown on the right-hand side, with 0 representing the worst experience ever, 5 representing a neutral experience, and 10 representing the best experience ever. The dotted red line marks the boundary between mildly unpleasant or worse (left of the line, score of 0–3) and acceptable scores (right of the line, score of 4 or more), for ease of comparison between the two procedures.</p