Daisy Elliott

Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians’ Practices across Six Randomised Controlled Trials

Background Randomised controlled trials (RCTs) are essential for evidence-based medicine and increasingly rely on front-line clinicians to recruit eligible patients. Clinicians’ difficulties with negotiating equipoise is assumed to undermine recruitment, although these issues have not yet been empirically investigated in the context of observable events. We aimed to investigate how clinicians conveyed equipoise during RCT recruitment appointments across six RCTs, with a view to (i) identifying practices that supported or hindered equipoise communication and (ii) exploring how clinicians’ reported intentions compared with their actual practices. Methods and Findings Six pragmatic UK-based RCTs were purposefully selected to include several clinical specialties (e.g., oncology, surgery) and types of treatment comparison. The RCTs were all based in secondary-care hospitals (n = 16) around the UK. Clinicians recruiting to the RCTs were interviewed (n = 23) to understand their individual sense of equipoise about the RCT treatments and their intentions for communicating equipoise to patients. Appointments in which these clinicians presented the RCT to trial-eligible patients were audio-recorded (n = 105). The appointments were analysed using thematic and content analysis approaches to identify practices that supported or challenged equipoise communication. A sample of appointments was independently coded by three researchers to optimise reliability in reported findings. Clinicians and patients provided full written consent to be interviewed and have appointments audio-recorded. Interviews revealed that clinicians’ sense of equipoise varied: although all were uncertain about which trial treatment was optimal, they expressed different levels of uncertainty, ranging from complete ambivalence to clear beliefs that one treatment was superior. Irrespective of their personal views, all clinicians intended to set their personal biases aside to convey trial treatments neutrally to patients (in accordance with existing evidence). However, equipoise was omitted or compromised in 48/105 (46%) of the recorded appointments. Three commonly recurring practices compromised equipoise communication across the RCTs, irrespective of clinical context. First, equipoise was overridden by clinicians offering treatment recommendations when patients appeared unsure how to proceed or when they asked for the clinician’s expert advice. Second, clinicians contradicted equipoise by presenting imbalanced descriptions of trial treatments that conflicted with scientific information stated in the RCT protocols. Third, equipoise was undermined by clinicians disclosing their personal opinions or predictions about trial outcomes, based on their intuition and experience. These broad practices were particularly demonstrated by clinicians who had indicated in interviews that they held less balanced views about trial treatments. A limitation of the study was that clinicians volunteering to take part in the research might have had a particular interest in improving their communication skills. However, the frequency of occurrence of equipoise issues across the RCTs suggests that the findings are likely to be reflective of clinical recruiters’ practices more widely. Conclusions Communicating equipoise is a challenging process that is easily disrupted. Clinicians’ personal views about trial treatments encroached on their ability to convey equipoise to patients. Clinicians should be encouraged to reflect on personal biases and be mindful of the common ways in which these can arise in their discussions with patients. Common pitfalls that recurred irrespective of RCT context indicate opportunities for specific training in communication skills that would be broadly applicable to a wide clinical audience.

An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment.

Objectives To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Study Design and Setting Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. Results One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was “best for them”. Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. Conclusions The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation.

Informed consent in randomised controlled trials: Development and preliminary evaluation of a measure of Participatory and Informed Consent (PIC)

BackgroundInformed consent (IC) is an ethical and legal prerequisite for trial participation, yet current approaches evaluating participant understanding for IC during recruitment lack consistency. No validated measure has been identified that evaluates participant understanding for IC based on their contributions during consent interactions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure for application to recorded recruitment appointments. The PIC allows the evaluation of recruiter information provision and evidence of participant understanding.MethodsPublished guidelines for IC were reviewed to identify potential items for inclusion. Seventeen purposively sampled trial recruitment appointments from three diverse trials were reviewed to identify the presence of items relevant to IC. A developmental version of the measure (DevPICv1) was drafted and applied to six further recruitment appointments from three further diverse trials to evaluate feasibility, validity, stability and inter-rater reliability. Findings guided revision of the measure (DevPICv2) which was applied to six further recruitment appointments as above.ResultsDevPICv1 assessed recruiter information provision (detail and clarity assessed separately) and participant talk (detail and understanding assessed separately) over 20 parameters (or 23 parameters for three-arm trials). Initial application of the measure to six diverse recruitment appointments demonstrated promising stability and inter-rater reliability but a need to simplify the measure to shorten time for completion. The revised measure (DevPICv2) combined assessment of detail and clarity of recruiter information and detail and evidence of participant understanding into two single scales for application to 22 parameters or 25 parameters for three-arm trials. Application of DevPICv2 to six further diverse recruitment appointments showed considerable improvements in feasibility (e.g. time to complete) with good levels of stability (i.e. test-retest reliability) and inter-rater reliability maintained.ConclusionsThe DevPICv2 provides a measure for application to trial recruitment appointments to evaluate quality of recruiter information provision and evidence of patient understanding and participation during IC discussions. Initial evaluation shows promising feasibility, validity, reliability and ability to discriminate across a range of recruiter practice and evidence of participant understanding. More validation work is needed in new clinical trials to evaluate and refine the measure further.

Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

BackgroundResearch has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment.MethodsEight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs.ResultsThe eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR – Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received.ConclusionsThe SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work to test it more widely is recommended.

PD56-08 THE PART TRIAL - A PHASE III STUDY COMPARING PARTIAL PROSTATE ABLATION VERSUS RADICAL PROSTATECTOMY (PART) IN INTERMEDIATE RISK PROSTATE CANCER – EARLY DATA FROM THE FEASIBILITY STUDY

INTRODUCTION AND OBJECTIVES: Salvage surgery is an option for recurrent prostate cancer(PCa) after focal therapy(FT). This is the first study to assess the impact of FT on surgical outcomes comparing salvage robotic-assisted radical prostatectomy(S-RARP) versus primary-RARP(P-RARP). We aimed to compare the impact of FT on perioperative, oncological and functional outcomes in men underwent S-RARP versus P-RARP. METHODS: Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-five men underwent S-RARP after FT failure(S-RARP group). Total 2750 underwent RARP as primary treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age, IPSS and IIEF5 defined P-RARP group. Primary endpoint was between-groups differences on functional outcomes. Secondary endpoint was oncological data. p<0.05 was significant. RESULTS: Surgical time, transfusion and complication rates were comparable(p 0.05). Rates of continence probability[49.5%(SE 0.13) versus 62.4%(SE 0.08), p1⁄40.8 and 73%(SE 0.14) versus 76.5%(SE 0.07), p1⁄40.8, at 1 and 2 years, respectively] and the chance for achieving continence[HR 1.062, 95%CI 0.54-2.08, p1⁄40.861] were comparable between-groups. Potency recovery was significant lower on S-RARP at 1 year follow-up[3 2 versus 9.22 6.55, p1⁄40.008]. S-RARP showed significant lower rates of cumulative BCR-free survival probability[67.6%(SE 0.12) versus 95.1%(SE 0.03), p1⁄40.001 and 56,3%(SE 0.15) versus 92,4%(SE 0.04), p1⁄40.001, at 1 and 2 years, respectively]. S-RARP presented significant increased risk of BCR[HR 4.8, 95%CI 1.67-13.76, p1⁄40.004]. Upstaging was an independent predictor factor for BCR on S-RARP[HR 14.65, 95%CI 1.46-146.37, p1⁄40.022]. CONCLUSIONS: Salvage-RARP following FT failure is feasible and safe with acceptable complications rates. Patients assigned to FT should be previously advised about lower erectile recovery rates in case of a salvage surgery. Urologists may be warned about the risk of undertreatment in patients presenting failure along FT follow-up. Source of Funding: None

Developing outcome measures assessing wound management and patient experience : a mixed methods study

Objectives To develop outcome measures to assess practical management of primary surgical wounds and patient experience. Design Mixed methods, including qualitative interviews and data extraction from published randomised controlled trials (RCTs). Setting Two university-teaching NHS hospitals and three district NHS hospitals in the South West and Midlands regions of England. Participants Sixty-four patients and 15 healthcare professionals from abdominal general surgical specialities and obstetrics (caesarean section). Methods Measures were developed according to standard guidelines to identify issues relevant to patients’ experiences of surgical wounds and dressings, including analysis of existing RCT outcomes and semi-structured interviews. These were written into provisional questionnaire items for a single outcome measure. Cognitive interviews with patients and healthcare professionals assessed face validity, acceptability and relevance. Findings from interviews were regularly shared with the study team who suggested amendments to modify and reword items to improve understanding before further iterative testing with patients and healthcare professionals. Results Analyses of existing RCT outcomes and interviews produced a total of 69 issues. Pretesting and iterative revision established the need for two separate measures. One measure addresses healthcare professionals’ experience of wound management in two key areas: exudate and its impact, and allergic reactions to the dressing. The other measure addresses patients’ experience of wounds in seven key areas: wound comfort, dressing removal, dressings to protect the wound, impact on daily activities, ease of movement, anxiety about the wound and satisfaction with dressing. Each measure took less than five min to complete and both were understood and acceptable to patients and healthcare professionals. Conclusion This in-depth study has developed two measures to assess practical management of primary surgical wounds and patient experience. Further work to test their validity, reliability and application to other settings is now required. Trial registration number HTA - 12/200/04; Pre-results.

The Quintet Recruitment Intervention supported five randomized trials to recruit to target: a mixed-methods evaluation

Objective To evaluate the impact of the QuinteT Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand recruitment difficulties and then implements “QRI actions” to address these as recruitment proceeds. Study Design and Setting A mixed-methods study, comprising (1) before-and-after comparisons of recruitment rates and the numbers of patients approached and (2) qualitative case studies, including documentary analysis and interviews with RCT investigators. Results Five UK-based publicly funded RCTs were included in the evaluation. All recruited to target. Randomized controlled trial 2 and RCT 5 both received up-front prerecruitment training before the intervention was applied. Randomized controlled trial 2 did not encounter recruitment issues and recruited above target from its outset. Recruitment difficulties, particularly communication issues, were identified and addressed through QRI actions in RCTs 1, 3, 4, and 5. Randomization rates significantly improved after QRI action in RCTs 1, 3, and 4. Quintet Recruitment Intervention actions addressed issues with approaching eligible patients in RCTs 3 and 5, which both saw significant increases in the number of patients approached. Trial investigators reported that the QRI had unearthed issues they had been unaware of and reportedly changed their practices after QRI action. Conclusion There is promising evidence to suggest that the QRI can support recruitment to difficult RCTs. This needs to be substantiated with future controlled evaluations.

Cataract surgery patient reported outcome measures: a head-to-head comparison of the psychometric performance and patient acceptability of the Cat-PROM5 and Catquest-9SF self-report questionnaires

Background Cataract surgery is the most frequently undertaken NHS surgical procedure. Visual acuity (VA) provides a poor indication of visual difficulty in a complex visual world. In the absence of a suitable outcome metric, recent efforts have been directed towards the development of a cataract patient-reported outcome measure (PROM) of sufficient brevity, precision, and responsiveness to be implementable in routine high volume clinical services.Aim To compare and contrast the two most promising candidate PROMs for routine cataract surgery.Method The psychometric performance and patient acceptability of the recently UK developed five-item Cat-PROM5 questionnaire was compared with the English translation of the Swedish nine-item Catquest-9SF using Rasch-based performance metrics and qualitative semistructured interviews.Results Rasch-based performance was assessed in 822 typical NHS cataract surgery patients across four centres in England. Both questionnaires demonstrated good to excellent performance for all metrics assessed, including Person Reliability Indices of 0.90 (Cat-PROM5) and 0.88 (Catquest-9SF), responsiveness to surgery (Cohen’s standardized effect size) of 1.45 SD (Cat-PROM5) and 1.47 SD (Catquest-9SF) and they were highly correlated with each other (R=0.85). Qualitative assessments confirmed that both questionnaires were acceptable to patients, including in the presence of ocular comorbidities. Preferences were expressed for the shorter Cat-PROM5, which allowed patients to map their own issues to the questions as opposed to the more restrictive specific scenarios of Catquest-9SF.Conclusion The recently UK developed Cat-PROM5 cataract surgery questionnaire is shorter, with performance and patient acceptability at least as good or better than the previous ‘best of class’ Catquest-9SF instrument.

Protocol for the systematic review of the reporting of transoral robotic surgery

Introduction Transoral robotic surgery (TORS) has been adopted in some parts of the world as an innovative approach to the resection of oropharyngeal tumours. The development, details and outcomes of early-to-later phase evaluation of this technique and the quality of evidence to support its adoption into practice have hitherto not been summarised. The aim of this review is to identify and summarise the early and later phase studies of, and evidence for, TORS and to understand how early phase studies report intervention development, governance procedures and selection and reporting of outcomes to optimise methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. The protocol has been written in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. Methods and analysis Electronic searches in OVID SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from the start of indexing to 30 April 2017 will identify studies reporting TORS. At least two independent researchers will identify studies for inclusion. Two researchers will extract data from each paper. Studies will be categorised into IDEAL stages of study design from ‘pre-IDEAL’ to randomised controlled trials (stage 3). Data will be collected about the (1) novel intervention and criteria for modification, (2) governance arrangements and patient information provision, (3) outcome domains selected and reported and (4) quality of study design, conduct and reporting. Descriptive statistics and a narrative synthesis will be presented. Ethics and dissemination The results of this systematic review will be presented at relevant conferences. The methods will be used to inform future reviews exploring other novel surgical innovations. The findings will be published in a peer-reviewed journal. This study does not require ethical approval.

Overcoming difficulties with equipoise to enable recruitment to a randomised controlled trial of partial ablation versus radical prostatectomy for unilateral localised prostate cancer

To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate‐risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment.