The main research question
Aims of the study
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To assess the efficacy of an intervention designed to:
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◦ elicit patients’ expectations of what reconstructive breast surgery will achieve
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◦ facilitate setting of patient-centred goals
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◦ facilitate discussion of these expectations and goals with the patient’s surgical team.
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To explore whether the PEGASUS intervention improves patient reported outcomes (Breast Q) and reduces decisional conflict amongst women offered the option of breast reconstruction.
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To explore the economic costs of delivering the PEGASUS intervention compared with the costs of treatment as usual.
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To explore patients’ and health professionals’ experiences of using the PEGASUS intervention and its implementation within breast reconstruction services.
The research will be overseen and informed by the expertise of an advisory group consisting of patient representatives, a surgeon, clinical psychologist, specialist nurse, breast cancer charity representative and members of the research team.
Design
A mixed methods (qualitative and quantitative methods), multi-centred, non-randomised between subjects, before-and-after design comparing usual care (control) with the intervention (PEGASUS). Randomised Controlled Trials (RCTs) are not necessarily suited for psychosocial research [28]. In this study it is inappropriate to randomize participants since contamination effects between conditions are likely if surgeons must focus some consultations around the patient goals offered by PEGASUS, but revert to usual care in others. In this non-randomised design, the control group comprises consenting patients receiving usual care. On completion of the control group recruitment, the health professionals receive PEGASUS training, prior to intervention group recruitment. Semi-structured interviews will be conducted with a selection of participants and health professionals involved in the PEGASUS intervention condition. Intervention consultations will be recorded (with permission) and assessed against a study-specific checklist to check the fidelity of the intervention.
Trial design characteristics
The characteristics of the PEGASUS trial were assessed using PRECIS-2 [29]. PRECIS-2 is a tool specifically designed to assess trial design on a continuum of pragmatic-explanatory across nine criteria: eligibility, recruitment, setting, organisation, flexibility delivery, flexibility adherence, follow-up, primary outcome and primary analysis. Pragmatic trials aim to explore whether an intervention works in real-life settings whereas exploratory trials aim to explore whether an intervention works under ideal conditions [29, 30]. Figure 1 illustrates the trial design based on the nine criteria. Eligibility, recruitment, setting, follow-up and primary analysis follow a pragmatic approach, whereas organisation, flexibility delivery, flexibility adherence and primary analysis fall along the pragmatic-explanatory continuum.
Sites
Data collection will take place at hospital sites (Bristol, Bath, Truro, Winchester, and Cardiff) with comprehensive breast reconstruction services. The researcher will maintain weekly contact with each site, where clinic staff will identify eligible participants, provide study information and give the researcher the details of those who consent to participate.
Sample size
One hundred eighty women over the age of 18 who have been diagnosed with breast cancer or DCIS (Ductal Carcinoma in Situ) or are seeking risk reducing surgery due to a strong family history of breast cancer, and who are considering breast reconstruction following mastectomy. We will record how many women are eligible for the study, how many participate and record reasons for refusal, where possible.
Power calculations
The primary outcome measure is the Breast-Q (breast reconstruction) [31] with psychosocial wellbeing, sexual well-being, physical well-being and 5 satisfaction subscales applicable pre- and post-op and an expectations subscale applicable pre-operatively only. Sample size has been determined to ensure the simple comparison between the two groups 3–month post-operatively has at least 90% power (beta <= .20) using contemporary levels of significance (alpha = .05) in a two-sided test as this will ensure similar power requirements will be met for within group comparisons and for the anticipated interaction effect in the two-way ANOVA. An a priori power analysis based on a two-sided application of the independent samples t-test with an assumed lower estimate of a medium effect size (Cohen’s d = 0.5) indicates that at least 90% power would be achieved with a sample size of n = 90 per group. This stated power equates to at least 75% of women doing better in PEGASUS than they would have done with treatment as usual.
Exclusion criteria
Women who, for any reason, are unsuitable for breast reconstruction or unable to participate in an intervention and study conducted in English will not be eligible to participate. We acknowledge this limitation, but do not currently have the resources needed to offer PEGASUS in other languages. If this study is successful we will explore its use with women with limited English proficiency (LEP) in future research.
Intervention training
Specialist nurses, psychologists and surgeons at each site will be trained to use PEGASUS by AC (the clinical psychologist in the study team) and the study researcher (NP). Face-to-face training will be supplemented by a manual and video footage demonstrating its use, accessible throughout the study. Feedback on this training (elicited in the health professional interviews and questionnaires at the training sessions) will identify whether edits are needed prior to making training resources available through the PEGASUS website (www.pegasusdecisionmaking.com) in any subsequent roll-out of the intervention.
Procedure (see Additional file 1)
Potential participants will be identified by clinic staff at each site from appropriate clinic lists.
At each participating site, the control group will be recruited before recruitment to the intervention condition begins. Staff will be trained in the use of the intervention once control group recruitment has been completed at their site.
Women identified as being eligible for the control (usual care) group will be given the study information sheet together with a consent form and questionnaire booklet and a stamped – return addressed envelope. Clinic staff will provide these materials and be on hand to address any questions from potential participants (and will contact the research team for assistance if there are any questions they are unable to answer).
Women identified as being eligible for the intervention group will be given the study information sheet, and the opportunity to ask questions about the study. Those interested in taking part will be given a consent form and an appointment at which they will complete the PEGASUS intervention - this appointment will be not less than 24 h after they have first been told about the study (exact details will depend on the specific study site).
During the intervention consultation, women who have chosen to take part in this study will have a discussion with the trained PEGASUS coach that will be aimed at clarifying their explicit goals and expectations about reconstructive surgery. Together, the coach and patient will complete the PEGASUS sheet – a single piece of paper which will summarise the conversation and list explicitly what the patient is hoping breast reconstruction will achieve. The participant will then take this PEGASUS sheet into their consultation with the breast reconstruction surgeon, who will have been trained to use the sheet, to encourage a discussion about the woman’s expectations, thereby framing the surgical discussion in terms of what it is that the patient is hoping to achieve.
We will seek consent from women in the intervention condition to record their PEGASUS consultations in order that we can assess the fidelity of the intervention.
We will ask all participants to complete the following self-report measures in the questionnaire booklet at baseline (i.e. pre-intervention for those in the PEGASUS condition, equivalent timing for those in the control condition) and 3, 6 and 12 months after surgery, together with visual analogue scales (VAS) to assess the extent to which expectations/goals have been met, and satisfaction with decision making and care. Measures will be available for completion in paper format and online. Statistical analysis will examine changes in the self-report scores over time.
Measures
Primary outcome measure
Breast-Q (reconstruction or mastectomy versions, as appropriate) [31] is a widely used measure of quality of life specific to breast reconstruction.
Secondary outcome measures
EQ-5D-5 L (a measure of health-related quality of life) [32] and ICECAP-A [33] capabilities (what participants want to be able to do in various key aspects of life), shared decision making (Decisional Conflict scale [34], CollaboRATE [35] and visual analogue scales) and Decisional Regret (Decisional Regret Scale) [36].
Cost-utility analyses will be undertaken from a funder perspective over the timeframe of the study. Resources used at each stage of shared decision making will be recorded using a study-specific resource use checklist tool, which will be used with prices from published sources to estimate unit costs. Costs will be expressed in 2017 prices and uprated in line with inflation. Funder incremental costs (shared decision making with PEGASUS versus usual care) will be related to incremental change in EQ-5D-5 L scores to estimate (cost per Quality adjusted Life Year gained):
• Cost per Quality-adjusted Life Year gained based on the EQ5DL scores
• Average cost of implementing PEGASUS per site
• Average cost per patient
• Cost per hour of shared decision making
Analysis
The analyses will be described in detail in a full Statistical Analysis Plan but, in brief, the design permits a robust statistical analysis using a linear mixed model with random intercepts for longitudinal data, a one-way ANCOVA with baseline pre-op measure as a covariate, and t-tests for prior reasoned group comparisons. An adjusted ANCOVA will be used to account for the between-subjects non-equivalent groups design and this will prevent an overestimation of treatment effect due to measurement error. Primary analyses will be performed under multiple imputation using Multiply Imputed Chained Equations (MICE) and repeated on a complete basis. Data validity checks and missing values analysis will be undertaken prior to descriptive and inferential analysis. PEGASUS is intended for use with any surgical group and we will compare delayed with immediate reconstruction patients for any systematic differences in outcome.
Interviews
We will conduct a nested qualitative study that will involve semi-structured interviews with around 32 patients (8 per site; 4 intervention, 4 control) and 20 health professionals (PEGASUS Coaches and surgeons; 5 per site), exploring experiences of PEGASUS (where appropriate), patients’ expectations of reconstruction and if these were met. Patient interviews will be conducted around the 12 month follow up data collection, using Breast-Q scores (high, middle, low) to purposefully sample to ensure interviews are conducted with patients with varying outcomes. Telephone interviews will be conducted if preferred by the patient or health professional, or if face-to-face is not possible. Face-to-face interviews will be conducted at a time and place of the interviewee’s choosing (following standard University protocols for safe lone working). Interview recordings will be transcribed verbatim and subjected to thematic analysis [37]. Findings will be agreed by the research team, with feedback from the advisory group. Participants’ goals and expectations on the PEGASUS forms will be subjected to content analysis.
Data storage/confidentiality
A data protection document describes the study’s safeguards for the storage and protection of confidential information, both held manually and on computers. This document is guided by the Caldicott principles for handling patient-identifiable information, The UK Data Protection Act (1998) [38] and Good Clinical Practice guidance [39]. All data will be treated as confidential. Only members of the research team who are also members of the breast reconstruction service at the participating sites will examine clinic and medical records in order to identify potential participants. Once consented, the research team based at the university may require access to participants’ medical records in order to collect and check health economic data. Permission to do this will be included on the participant consent form. Audio files (interviews and consultation recordings) and data will be stored on a password protected computer accessible only by the research team. Completed questionnaires and consent forms will be stored separately, in a locked filing cabinet.
Research governance, safety and the conduct of the study
It was agreed that an independent data monitoring committee was not necessary and interim analyses will not be conducted. A PEGASUS steering group will be set up with an independent chair and members and will meet every 6 months. The steering group will provide advice and supervision of the study and will focus on the progress of the study, approaches to improve adherence, the collection of follow-up data, participant safety and consideration of new information. The management team (consisting of the principle investigator, clinical psychologist, researcher, health economist and statistician) will meet once-a-month to discuss study progress, protocol adherence and amendments for ethical approval. Access to the final dataset will be restricted to members of the study management group.
Dissemination of research findings
Members of our steering and management groups will provide expert advice on the dissemination of the main outcomes to participants. The findings of this study will be disseminated via publications in peer-reviewed journals. Dissemination of the findings to health professionals and organisations supporting women with breast cancer will be planned and developed with stakeholders throughout the study.
Study approvals
This study has been approved by the NRES Committee South Central - Berkshire B (reference 15/SC/0331) and the Faculty of Health and Applied Sciences Research Ethics Committee at the University of the West of England, Bristol. All necessary R&D approvals have been granted by the NHS study sites. The study has been accepted on the National Institute for Health Research (NIHR) Clinical Research Network (CRN) Portfolio.
Research Sponsor: University of the West of England, Bristol.
Timeframe of the study
The trial started on the 1st of July 2015 and will be completed in June 2019.