open access protocol improving the well-being of men...

Improving the well-being of men byEvaluating and Addressing theGastrointestinal Late Effects (EAGLE)of radical treatment for prostate cancer:study protocol for a mixed-methodimplementation project

Sophia Taylor,1 Weyinmi Demeyin,2 Ann Muls,3 Catherine Ferguson,4

Damian J J Farnell,5 David Cohen,6 Jervoise Andreyev,3 John Green,7

Lesley Smith,8 Sam Ahmedzai,9 Sara Pickett,10 Annmarie Nelson,1 John Staffurth11,12

To cite: Taylor S,Demeyin W, Muls A, et al.Improving the well-being ofmen by Evaluating andAddressing theGastrointestinal Late Effects(EAGLE) of radical treatmentfor prostate cancer: studyprotocol for a mixed-methodimplementation project. BMJOpen 2016;6:e011773.doi:10.1136/bmjopen-2016-011773

Prepublication history andadditional material isavailable. To view please visitthe journal (http://dx.doi.org/10.1136/bmjopen-2016-011773).

Received 3 March 2016Revised 13 May 2016Accepted 20 June 2016

For numbered affiliations seeend of article.

Correspondence toDr Annmarie Nelson;[email protected]

ABSTRACTIntroduction: Radiotherapy treatment for prostatecancer can cause bowel problems, which may lead tosevere difficulties for cancer survivors includinglimiting travel, work or socialising. These symptomscan appear at any time following radiotherapy.This study focuses on the early identification andprotocol-based management of effects known to causelong-term, or even permanent, changes to thewell-being of prostate cancer survivors. The rationaleof this study is to improve the care offered to menand their families following pelvic radiotherapy forprostate cancer.Method and analysis: Implementation researchmethodology will be used to adopt a multicomponentintervention at three UK centres. The interventionpackage comprises a standardised clinical assessmentof relevant symptoms in oncology outpatient clinicsand rapid referral to an enhanced gastroenterologicalservice for patients identified with bowel problems.Gastroenterology staff will be trained to use an expert-practice algorithm of targeted gastroenterologyinvestigations and treatments. The evaluation of theintervention and its embedding within local practiceswill be conducted using a mixed-methods design. Theeffect of the new service will be measured in terms ofthe following outcomes: acceptability to staff andpatients; quality of life; symptom control and cost-effectiveness. Data collection will take place at baseline,6 months (2 months), and 12 months (2 months)after entry into the study.Ethics and dissemination: The study has ethicalapproval from the North West-Liverpool East ResearchEthics Committee and the appropriate NHS governanceclearance. All participants provide written informedconsent. The study team aim to publish the results ofthe study in peer-reviewed journals as well as atnational and international conferences.Trial registration number: UKCRN16974

INTRODUCTIONProstate cancer is the most common cancerin men in the UK except for non-melanomatous skin cancer. Indeed, 47 300men were diagnosed in the UK with prostatecancer in 2013.1 Men with organ-confinedlocalised disease have extremely good short-term prostate cancer survival rates with over95% alive at 5 years after diagnosis and 84%at 10 years.1 2 There are several radical treat-ment options available for prostate cancer.Much evidence exists relating to the short-term and long-term effects of the majorestablished therapies (prostatectomy, exter-nal beam radiotherapy and low-dose ratebrachytherapy).3 Despite these side effects oftreatment, many men remain satisfied withtheir treatment and they would select thesame treatment again.4

Late effects of pelvic radiotherapyRadiotherapy is important in the treatmentof cancers.5 It is estimated conservatively that

Strengths and limitations of this study

The study uses mixed methods, using bothqualitative and quantitative approaches to datacollection and analysis enabling solutions to anyproblems that arise can be made in real time.

The study is restricted to the recruitment ofpatients with prostate cancer with late gastro-intestinal effects of pelvic radiotherapy, therebyreducing the sample size and generalisability toother cancer diagnoses and treatment modalities.In addition, the implementation of the interven-tion may not be successful.

Taylor S, et al. BMJ Open 2016;6:e011773. doi:10.1136/bmjopen-2016-011773 1

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17 000 patients with cancer receive pelvic radiotherapyper year in the UK.6 Of these an estimated 90% developa permanent change in their bowel habit and 50%experience a reduction in their quality of life, and 2040% rate the effect on quality of life as moderate orsevere.7 In a more recent study 35% of prostate patientswith cancer suffered from bowel urgency 15 years afterradiotherapy.8

Despite the significant impact of these symptoms onquality of life, only one in five patients who developgastrointestinal (GI) symptoms after pelvic radiotherapyare referred to a gastroenterologist.9 There are severalreasons for this low referral rate. First, patients may notoffer up their symptoms to the treating doctor, despitethe potentially catastrophic effects to their physical, emo-tional and social well-being. Explanations for this behav-iour include reasons such as: patients may view them asexpected consequences of therapy; they may be tooembarrassed to mention them; or, they might just begrateful for being cured.10 Second, clinicians lookingafter patients might not seek information on late radi-ation effects, focusing primarily on symptoms of cancer,partly as late effects have been considered to beirreversible.11

Current patterns of careThe long-term care of men with curable or cured pros-tate cancer varies between countries. There are alsointracountry variations, particularly in the UK wherehealthcare has been devolved.12 Variations in managinglate GI effects of pelvic radiotherapy across the UK havebeen highlighted by two recent surveys of patterns ofcare aimed at clinical oncologists and gastroenterolo-gists.6 13 The oncologist survey reported that 91 of 190(48%) responding clinicians refer

To assess the effectiveness of training in relation tosafe and independent coordination of services.

The interventionThe proposed intervention (outlined in figure 1) is apackage of multidisciplinary care aimed at the earlyidentification and the subsequent intervention to reducethe physical, psychological and social impact of late GIeffects after curative treatment for prostate cancer.

Study designThe Evaluating and Addressing the Gastrointestinal LateEffects (EAGLE) study is a mixed methods implementa-tion study. The study involves the development of a newpackage of enhanced assessment, multidisciplinary careand use of treatment algorithms will be assessed withinan implementation-research framework. Implementationresearch can be defined as the scientific inquiry intoquestions concerning implementationthe act of carry-ing an intention into effect, which in health researchcan be policies, programmes or individual practices (col-lectively called interventions).15 The success of theimplementation is based on real-world outcomes; accept-ability; adoption; appropriateness; feasibility; fidelity;implementation cost; incremental cost of interventiondelivery and costs to other NHS services; coverage;sustainability.16

Outcomes will be measured via collection and analysisof both quantitative and qualitative data sets. Mixed

methods are suitable for implementation research asthey provide a practical way to understand multiple per-spectives and outcomes.15 This approach will involve aquantitative before and after (treatment) study, as well asa substudy involving the use of a comparison group anda qualitative study.This study will use an overarching framework suited to

complex interventions called normalisation processtheory (NPT).17 NPT is a pragmatic theory that exam-ines the factors needed for successful implementationinto local practice. NPT allows one to examine thosefactors that are essential for new initiatives in healthcaresettings where multiple stakeholders perspectives andresource availability can sink new developments or canundermine trials.18 Murray et al18 and Meyer et al19 dis-cussed the role of NPT in testing the feasibility, adher-ence and acceptance of initiatives. These analyses werecoupled with an evaluation of cost and sustainability persite, albeit with scope for local idiosyncrasies.

Implementation centresThis study will be carried out in three centres across theUK. Sites will be invited to complete a template of exist-ing services to apply for selection to the study (seeonline supplementary file 1 for an example of the siteinformation form).Criteria for site selection:

Clinical oncology team (from the same catchmentarea as the gastroenterology team) managing around100 patients per year with prostate cancer who havebeen treated with radical radiotherapy.

Ability to identify a prostate-cancer oncologist willingto use the Assessment of Late Effects ofRadioTherapy-Bowel (ALERT-B) screening tool toidentify and recruit patients for the EAGLE study.

Ability to identify a gastroenterologist who is willingto: Support the introduction of a non-consultant post

following the Guide to Managing GastrointestinalSymptoms of Pelvic Radiation Disease for investiga-tion and management of pelvic radiation disease;20

Provide ongoing clinical support to the non-consultant postholder;

Adhere to the RMH algorithm; Lead the local process for securing sustainable

funding. Additional key considerations include ongoing local

developments in this field including involvement ofoncologists managing patients with other cancerswho are known to suffer pelvic radiation disease(PRD).

Enhanced staff trainingTraining options for the specialist PRD team will includecompletion of the Macmillan Cancer Support-RMHonline training module, teaching and support sessionswith the RMH nurse consultant, and visits to the RMHPRD multidisciplinary clinic to gain experience of how

Figure 1 Summary of the intervention. The figure offers abreakdown of the gastrointestinal intervention provided as partof the study. Patients will be screened for late gastrointestinaleffects in oncology using a simple screening tool,ALERT-B. Patients with symptoms will then be referred togastroenterology to a specialist team who will follow analgorithm to offer targeted investigations and treatment.ALERT-B, Assessment of Late Effects ofRadioTherapy-Bowel; EAGLE, Evaluating and Addressing theGastrointestinal Late Effects study; GI, gastrointestinal.


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the PRD service is delivered at the RMH. The GI andnutrition team at the RMH have developed a robustteaching package and supportive documentation fornew units. This teaching programme is supported by anonline validated BSc/MSc module run by The RoyalMarsden School. This training package will be aimed atboth the specialist PRD team and the wider non-specialist oncological and gastroenterological teams.Once a service is established, intermittent multidisciplin-ary update sessions (at least annually) will be providedto ensure that skills are maintained. These update ses-sions will be provided within EAGLE by ongoing supportfrom the RMH PRD multidisciplinary team (MDT) forthe duration of the study.

Enhanced MDT careA streamlined referral pathway to a named healthcareprofessionals in the new multidisciplinary PRD service ineach centre will be established for EAGLE study partici-pants who are identified with late GI effects of pelvicradiotherapy. The referral will include relevant oncologyand radiotherapy treatment information. During thefirst appointment at the new gastroenterology clinic, acomprehensive medical history will be taken. Detailedgastroenterological status will be ascertained by followingthe RMH algorithm, which will be used to arrangeappropriate investigations.9 A list of investigations can befound in online supplementary file 2.Follow-up investigations will be arranged by telephone

or clinic visits as necessary, although it is envisaged thatpatients will be seen in clinic at a minimum of 6 and12 months after initial assessment. Staffing, coordinationand running of enhanced services will be agreed on asite-by-site basis, according to local preferences. Theresearch team will liaise with these sites to create proto-cols for practice that are agreed locally, as required.

Participant selection and recruitmentEstablishing patient eligibility will be a two-stage process.Initially, those patients attending urology/oncologyfollow-up clinics that received radiotherapy treatmentfor prostate cancer at least 6 months previously will beasked to consent to the registration phase of EAGLE bya Good Clinical Practice (GCP) trained healthcare pro-fessional working at the oncology clinic.Those patients who consent will be screened for eligi-

bility by completing the ALERT-B tool. The ALERT-Btool (see online supplementary file 3) has been devel-oped and tested for content and face validity,21 bymembers of the EAGLE research team previously as partof a Tenovus Innovation Grant. As part of the EAGLEstudy, the ALERT-B tool will also be validated in terms ofreliability against the Gastrointestinal Symptom RatingScore (GSRS).The ALERT-B tool will be reviewed with the patient by

the clinical nurse specialist (CNS), research nurse,research radiographer or doctor. Those patients with atleast one yes response to one of the three questions

(experiencing faecal incontinence, rectal bleeding orsignificant impact on quality of life) will be identified tothe consultant oncologist and they will be registered forthe EAGLE study. Patients will be offered the choice tobe referred to the multidisciplinary pelvic disease clinicand they will be given written information about theEAGLE study.At both stages, patients will be excluded if they meet

one or more of the following criteria: any factor thataffects their ability to communicate their wishes; aninability to comprehend what is being asked of them; alack of capacity to consent; or, cancer recurrence.To benefit the maximum number of men, patients will

be recruited until the local gastroenterology service cap-acity is reached. It is estimated that 100 patients fromeach centre will be screened annually and those patientswho are referred will be managed within the service for12 months with an average of three appointments duringthis time. Long-term, the expectation is that a full-timeCNS would manage 150 new patients per year.

Participants for interviewsParticipants will be sampled purposively from the threeresearch sites across three groups to represent:1. Oncology and GI HCPs in order to capture staff atti-

tudes to implementation;2. Patients receiving services in order to capture patient

experience of services;3. Support givers to the family in order to represent

family or caregiver perspectives of services.The study aims to recruit 1015 participants from

each of the three groups listed above. Participants willbe interviewed at three time points over the course of 814 months. Interviews will also be conducted with keyinformants on a local basis, where appropriate. Forexample, these informants include primary care provi-ders and other stakeholders including MacmillanCancer Support services, commissioners and LocalHealth Board representatives.Participants must be aged 18 years and over and they

must be able to undertake an interview in Englishwithout the need for translation (unless local translationservices are readily available) in order to be eligible forinclusion in the study. All those participants who are eli-gible will be asked to participate until enough partici-pants have been recruited to represent each group (ie,until saturation) and to allow for follow-up interviews.Participants will be interviewed by either a face-to-faceinterview at a location of their choice or over the tele-phone. Interviews will last 3060 min. The interview willbe terminated earlier if a participant is thought to be fati-gued, upset or becomes unwell. In the event of partici-pant distress due to discussion of sensitive topics, or if aclinical or work-related issue emerges, the researchers,will react at the time according to their own experience.The researchers will then refer the issue to the partici-pants clinical team (with the participants permission).

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Data collectionData will be collected at baseline, 6 months (2 months)and 12 months (2 months) after entry into the study bya member of the research team. The diagram below(figure 2) demonstrates the pathway that EAGLE partici-pants will follow and the data collection instruments thatwill be used in the study. A case report form for eachassessment point will be assigned to each participant inorder to collect questionnaire and relevant clinical data.There are multiple (end point) domains to be consid-

ered including: physical; psychological; sexual; financial;and, social domains. There is some level of interdepend-ence and overlap between these domains. The study willfocus initially on physical effects, which can be broadlyseparated into gastrointestinal, genitourinary, sexual,endocrinal and fatigue. The study end points aredesigned to capture acceptability and effectiveness ofthe intervention and are as follows: Bowel-specific health-related quality of life (HRQoL); Global HRQoL; Prostate-specific HRQoL; Patient, support giver and staff experience; Healthcare resource usage; Cost and acceptability of staff training.

Bowel-specific HRQoLThe GSRS is a validated questionnaire addressing symp-toms that are important and relevant to patients withgeneral GI symptoms. GSRS evaluates the absence orpresence (and severity) of 15 GI symptoms using a four-point response scale over a 1-week period prior toadministration. GSRS assesses five domains that havebeen identified as important to GI integrity: reflux syn-drome; acute pain syndrome; indigestion syndrome;diarrhoea syndrome; and, constipation syndrome. GSRShas a range of scores going from zero to three (zerorepresenting good health and three poor health). Thisquestionnaire was chosen for use in this study becauseits reliability and validity are well-documented andnormal values for a general population are available.22

Global HRQoLGlobal HRQoL will be measured using the EQ-5D-5Land the European Organisation for Research andTreatment of Cancer Quality of Life Core Questionnaire30 (EORTC QLQ C30).A newly released validated version of the EQ-5D-5L

with five response categories (mobility, self-care, usualactivities, pain/discomfort and anxiety/depression) foreach dimension provides enhanced discriminatorypower will be used in the study.23 This tool also measuresHRQoL using a vertical visual analogue scale.24

The 30-item questionnaire incorporates five functionalscales and is a reliable and clinically valid measure ofquality of life in patients with cancer.25 Participants willbe asked to complete a number of questionnaires, and soto limit the burden of this process they will be required toanswer only questions 29 and 30 (ie, items that rate

overall global health and quality of life) from the EORTCQLQ C30 questionnaire. Item responses to these twoquestions from the EORTC QLQ C30 questionnaire arenumerical scales going from 1 to 7. The scores from bothitems are added together and their sum is transformedlinearly to lie in the range 0100, where 0 represents theworst possible global HRQoL and 100 represents the bestpossible global HRQoL.

Prostate-specific HRQoLProstate-specific HRQoL will be measured using theEuropean Organisation for Research and Treatment ofCancer Quality of Life Questionnaire Prostate Cancermodule (EORTC QLQ-PR25) and the ExpandedProstate Cancer Index Composite (EPIC-26). Both pros-tate questionnaires were requested by the funder,Prostate Cancer UK (PCUK), to collect data as part of aseries of global projects.The EORTC QLQ-PR25 questionnaire contains 25

items that are grouped into 5 multi-item scales. Highscores reflect either more symptoms (urinary, bowel,hormonal treatment-related symptoms) or high levels offunctioning (sexual).26 All items and scale scores of theEORTC QLQ-PR25 are transferred linearly onto a 0100scale, with higher scores again reflecting either moresymptoms (urinary, bowel, hormonal treatment-relatedsymptoms) or higher levels of functioning (sexual).24 Ashorter 26-item version of EPIC was designed and vali-dated.27 EPIC-26 has shown satisfactory testretest reli-ability and internal consistency for the urinary, bowel,sexual and hormonal domains.28

AcceptabilityExperience of the new service will be explored via longi-tudinal semistructured interviews with participants. Thedata obtained from these interviews will be used to high-light problems or to inform necessary adjustments of GIsymptom screening and the new gastroenterologyservice. In addition interviews with participants andsupport givers will provide an insight into the psycho-logical and social impact of GI symptoms and the newGI service. At the time of completion of the study, ananalysis will be carried out of all of the data sets in orderto report common themes and differences across partici-pant groups and settings. This analysis will contribute toa model of implementation for future sites in the UK.

Health resource usageResources used to deliver the intervention in all of thecentres will be monitored prospectively, including thoseresources used in training staff, screening patients andall patient contact, investigations, etc. Research costswill be isolated and they will not be included in thecosting.Resource usage data will be collected via two bespoke

resource-use questionnaires. One questionnaire will becompleted by all participants and the other question-naire will be completed by designated health


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professionals. Both questionnaires will be administeredat baseline and at each follow-up point. Patient recallhas been shown to be a valid method for collecting NHSresource-use data.29

Comparative patient dataComparative patient subsequent resource use data willbe collected from a Cardiff subgroup. Participants in thesubstudy will be managed following current standard

care, either within the Velindre Cancer Centre or withreferral to gastroenterology services in Cwm Taf. Datafrom this group will help to compare the impact of thenew GI service against standard care. These patients willbe given information on the substudy, which will involvean assessment of their healthcare resource usage andhealth-related quality of life over a 12-month periodfrom study entry. The EQ-5D-5L and EPIC-26 will alsobe completed at each data collection point.

Figure 2 EAGLE study Pathway. The figure provides an overview of the study processes and data collection at different stagesof the EAGLE study. Participants will consent to be screened for the late gastrointestinal effects of radiotherapy at their routineoncology appointments. Only patients identified with bowel symptoms will be offered a referral to gastroenterology where consentwill be taken for questionnaire data collection at three time points (baseline, around 48 months and 1014 months). ALRT-B,Assessment of Late Effects of RadioTherapy-Bowel; CNS, clinical nurse specialist; EAGLE, Evaluating and Addressing theGastrointestinal Late Effects study; HRQoL, health-related quality of life; GSRS, Gastrointestinal Symptom Rating Score.


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Data analysisParticipant and treatment characteristics will beexplored by using descriptive statistics. Measures ofcentre (mean and median) and measures of spread (SDand IQR) will be used to characterise outcome mea-sures. Subscale, and any appropriate overall scores, willbe found according to relevant scoring manuals (eg, forEORTC QLQ-C3030 or EPIC31) and with the use of anypre-existing and tested software (eg, in R using the pre-existing package QoLR for EORTC QLQC30 andPR25). Improvement in outcomes will be reported bycomparing the 6 and 12-month follow-up measures tothe baseline measurements and to the shadow compari-son group. Effect sizes such as standardised means frompretreatment to post-treatment (for 6 months post via,eg, (mean baselinemean 6 post)/SD baseline) will beused to characterise these improvements. Standardmethods for comparing paired or repeated-measuresdata will be employed in order to test if improvementsare statistically significant at the 5% level (eg, pairedtests and repeated-measures analysis on variance usingparametric or non-parametric methods, as appropriate).All participants will be encouraged to complete all ofthe questionnaires at all of the time points, and so it isimagined that complete-case analysis can be employed.A generic procedure will be used for missing data that

forms subscale scores from those items (appropriatelyweighted) in a subscale that are non-missing, if no morethan 50% of items in the subscale are missing. If morethan 50% of items are missing then the subscale score isalso set to be missing. This process accounts for item-wise missing data when forming subscale scores foreach patient, although it does not account for any attri-tion of patients during the study. If attrition from thestudy does occur (eg, through cancer recurrencethrough the course of the intervention, unacceptabilityof the intervention to some men, or burden of theresearch) then appropriate statistical modelling techni-ques that account for this effect and/or the use ofimputation techniques (eg, multiple imputation) can beemployed.

Cost-effectiveness analysisA cost-effectiveness analysis in the form of a cost utilityanalysis, comparing participants in the EAGLE studywith those not receiving the service will be undertakenfrom an NHS perspective for the primary analysis. Totalcosts (intervention plus or minus any subsequent differ-ences in NHS costs) will be assessed against effects interms of quality adjusted life years (QALY) based on theEQ-5D-5L. The estimated incremental cost per QALYfrom the service can be compared with the willingnessto pay threshold of 20 00030 000 per extra QALY cur-rently used by The National Institute for Health andCare Excellence (NICE).32

Secondary analysis will take a wider perspective andwill include missed workdays and patient-borne costs(including out-of-pocket expenses relating to travel,

carer provision and incontinence products). The sensi-tivity of the conclusions to changes in assumptions willbe assessed via sensitivity analysis.

Costing staff trainingProfessionals delivering the intervention will be asked tocomplete a training record on a weekly basis throughoutthe duration of the research study. This record will facili-tate measurement of training costs, which will feed intothe cost-effectiveness analysis. All formal training, in add-ition to more ad hoc training and support from dieti-cians, consultants or other healthcare professionals, willbe logged regardless of whether it is received during oroutside of working hours.

Interview data analysisThe researcher will audio record the interview digitally.Interviews will be transcribed verbatim and the interviewdata will be uploaded to qualitative analysis softwarecalled QSR NVivo V.10. Ten per cent of transcripts willbe co-coded by a senior researcher as a measure of reli-ability. Each interview will be read initially with a deduct-ive approach to isolate significant problem areas in theimplementation delivery. The anonymised data will berepresented by selected extracts in a narrative formatwith a thematic structure.Data will be analysed in order to identify problems

with local systems and procedures. This analysis will alsoexplore the HCP and patient and support giver attitudesand experiences. Framework analysis is the most appro-priate analytic method to achieve these aims for theinterview data.27 Framework analysis is suited to appliedhealth research in which a certain amount of existingknowledge is available and where the aim of the study isto inform future practice rather than theoretical devel-opment.33 Framework analysis involves a systematicprocess of sifting, charting and sorting the material intokey issues and themes.27 It allows the integration of apriori issues into the emerging data analysis and it pro-vides a clearly defined analytical structure that contri-butes to the transparency and validity of the results. Thematrix for the framework analysis will be developedfrom a deductive approach using NPT, further sup-ported by an overall inductive analysis of spontaneouslyarising themes during interviews.34

Project managementA study management group (SMG) will be responsiblefor the day-to-day management of the study and they willmeet regularly to advise on the promotion and runningof the study. SMG members will include the chief investi-gator (CI), coinvestigators, project staff and patientrepresentatives. Members will sign a SMG charter outlin-ing their roles. The study will be coordinated throughthe Marie Curie Palliative Care Research Centre.


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ConsentSigned consent will be taken at least 24 hours after thepatient has been given the relevant participant informa-tion sheet.A separate information and consent process to the

main study will be used for interviews as this is a subsetof the main study. The principal investigator or clinicalteam at each site will identify and discuss the interviewsubstudy with eligible patients, support givers and HCPsbefore consent can be obtained. Similarly, the partici-pant will remain free to withdraw at any time from thestudy. All data will be withdrawn at request.

Confidentiality and data managementThe CI and the research team of EAGLE will preservethe confidentiality of participants in accordance with theData Protection Act 1998.35 Data will be stored on apassword-protected computer located in secureUniversity buildings and appropriately backed up. Alldata will be retained for up to 15 years after the closureof the study.

ETHICS AND DISSEMINATIONEthical issuesCurrently only a small proportion of patients arereferred to a gastroenterologist for further investigationinto bowel symptoms that develop after pelvic radiother-apy. This may be because patients feel uncomfortablediscussing their bowel symptoms with healthcare profes-sionals.10 The SMG will draw on their considerableexperience in conducting research in this area to ensurea design sensitive to this patient group.Research data and patient-related information will be

managed in accordance with relevant regulatoryapprovals. The study has been adopted onto the UKClinical Research Network (UKCRN) portfolio under IDnumber 16974. In addition the study is sponsored byCardiff University (SPON1238-14).

Public and patient involvementPublic and patient involvement has been integral to theconduct of this study from the initial funding applica-tion. The SMG includes two research partners who havepersonal experience of the effect that late GI effects ofpelvic radiotherapy can have on the patient and theirfamily and friends. The research partners provide a valu-able source of experience that has particularly helpedwhen drafting appropriate participant-facing study docu-ments. Members of the research team will work along-side the research partners to identify and addressspecific support or training requirements to enable theireffective participation.

Methods of disseminating the findingsMultiple methods of disseminating the findings willinclude a written report for the study funders, PC UK,including an executive summary with clearly identified

practice suggestions to benefit patients, support giversand HCPs. The study will adhere to PCUK data sharingagreement with the National Cancer Research Institute(NCRI). As PCUK is a member of the NCRI, an agree-ment is in place to share anonymous data on the researchportfolio with the International Cancer ResearchPartnership (ICRP). Papers detailing the results of thisstudy will be submitted for publication in peer-reviewedjournals and at national and international conferences.Participants (or their families) will be informed on

request about the progress of the study. Summary reportswill be displayed on the website, although patients ortheir families will be able to request hard copies if theyprefer. For reasons of confidentiality, original data(audio recordings) and transcripts will not be shared.

Author affiliations1Marie Curie Palliative Care Research Centre, School of Medicine, CardiffUniversity, Cardiff, UK2Specialist Unit for Review Evidence, Cardiff University, Cardiff, UK3Gastroenterology Unit, Royal Marsden Hospital, London, UK4Department of Oncology, Weston Park Hospital, Sheffield Teaching HospitalsNHS Foundation Trust, Sheffield, UK5School of Dentistry, Cardiff University, Cardiff, UK6Faculty of Life Sciences and Education, Health Economics and PolicyResearch Unit (HEPRU), University of South Wales, Cardiff, UK7Department of Gastroenterology, University Hospital of Llandough, Cardiff,UK8Macmillan Cancer Support, London, UK9Department of Oncology, University of Sheffield, Sheffield, UK10Swansea Centre for Health Economics, College of Human and HealthSciences, Swansea University, Swansea, UK11Velindre Cancer Centre, Cardiff, UK12Institute of Cancer and Genetics, Cardiff University, Cardiff, UK

Twitter Follow Annmarie Nelson at @annmarie0

Contributors JS and AN are responsible for the overall design of the study.JA, JG, AM, SA, CF, DC, LS and SP are the coinvestigators. ST, DJJF and WDdrafted the manuscript. All authors provided input into the protocol, criticalfeedback on the manuscript and approved the final manuscript. The studysponsor and funder were not involved in the study design or writing of theprotocol.

Funding This work is supported by Prostate Cancer UKs True NTH initiative.The funder reference number is 250-55. ANs post is fully supported by MarieCurie Cancer Care core grant funding, grant MCCC-FCO-14-C.

Competing interests None declared.

Patient consent Obtained.

Ethics approval This study has gained approval from NHS Research EthicsCommittee (REC) NRES Committee North West-Liverpool East REC Reference14/NW/1206 and NHS Research and Development (NHS R&D) approvalfrom the sites.

Provenance and peer review Not commissioned; externally peer reviewed.

Open Access This is an Open Access article distributed in accordance withthe Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, providedthe original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation projectAbstractIntroductionLate effects of pelvic radiotherapyCurrent patterns of careManaging late GI effects of pelvic radiotherapyResearch required

Methods and analysisAims and objectivesThe interventionStudy designImplementation centresEnhanced staff trainingEnhanced MDT careParticipant selection and recruitmentParticipants for interviewsData collectionBowel-specific HRQoLGlobal HRQoLProstate-specific HRQoLAcceptabilityHealth resource usageComparative patient dataData analysisCost-effectiveness analysisCosting staff trainingInterview data analysisProject managementConsentConfidentiality and data management

Ethics and disseminationEthical issuesPublic and patient involvementMethods of disseminating the findings

References

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