STUDY PROTOCOL Open Access

Evaluation of a novel information resourcefor patients with bronchiectasis: studyprotocol for a randomised controlled trialKaty L. M. Hester1*, Julia Newton2, Tim Rapley3 and Anthony De Soyza1,4

Abstract

Background: There is currently little patient information on bronchiectasis, a chronic lung disease with risingprevalence. Previous work shows that patients and their families want more information, which could potentiallyimprove their understanding and self-management. Using interviews and focus groups, we have co-developed anovel patient and carer information resource, aiming to meet their identified needs.The aims and objectives are:1. To assess the potential impact of the information resource2. To evaluate and refine the intervention3. To establish the feasibility of carrying out a multi-centre randomised controlled trial to determine its effect onunderstanding, self-management and health outcomes

Methods/design: This is a feasibility study, with a single-centre, randomised controlled trial design, comparing useof a novel patient information resource to usual care in bronchiectasis. Additionally, patients and carers will beinvited to focus groups to discuss their views on both the intervention itself and the trial process.The study duration for each participant will be 3 months from the study entry date. A total of 70 patients will berecruited to the study, and a minimum of 30 will be randomised to each arm. Ten participants (and their carers ifapplicable) will be invited to attend focus groups on completion of the study visits. Participants will be adults withbronchiectasis diagnosed as per national bronchiectasis guidelines.Once consented, participants will be randomised to the intervention or control arm using random permuted blocksto ensure treatment group numbers are evenly balanced. Randomisation will be web-based. Those randomised tothe intervention will receive the information resource (website and booklet) and instructions on its use. Outcomemeasures (resource satisfaction, resource use and alternative information seeking, quality of life questionnaires,unscheduled healthcare visits, exacerbation frequency, bronchiectasis knowledge questionnaire and lung functiontests) will be recorded at baseline, 2 weeks and 3 months.

Discussion: All outcome measures will be used in assessing feasibility and acceptability of a future definitive trial.Feasibility outcomes include recruitment, retention and study scale form completion rates. Focus groups willstrengthen qualitative data for resource refinement and to identify participant views on the trial process, which willalso inform feasibility assessments. Questionnaires will also be used to evaluate and refine the resource.

Trial registration: ISRCTN84229105

Keywords: Bronchiectasis, Exacerbation, Self-management, Education, Information, Randomised controlled trial,Feasibility study, Qualitative research

* Correspondence: katy.hester@ncl.ac.uk1Institute of Cellular Medicine, Newcastle University, Newcastle upon TyneNE2 4HH, UKFull list of author information is available at the end of the article

© 2016 Hester et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Hester et al. Trials (2016) 17:210 DOI 10.1186/s13063-016-1330-4

BackgroundBronchiectasis is a chronic lung condition, characterisedby dilated bronchi, leading to symptoms of breathlessnessand chronic productive cough, with intermittent infectiveexacerbations. Bronchiectasis has various potential aetiol-ogies including immune deficiency syndromes, chronicasthma, chronic obstructive pulmonary disease, ciliarydysfunction and post-infectious causes, yet studies havefound that between a quarter and half of cases are idio-pathic [1, 2]. Patients often have recurrent, costly hos-pital admissions, a poorer quality of life [3, 4] andclinically significant fatigue [5, 6].Current estimates suggest a rise in prevalence in the

UK and indicate a prevalence of between 43.4/100,000in those aged 18–30 and 1239.7/100,000 in those aged70–79 [7]. Importantly, studies demonstrate that up to50 % of patients with chronic obstructive pulmonary dis-ease (COPD) have co-existent bronchiectasis [8]. Thereare approximately 1,000,000 patients with COPD in theUK [9]; thus there is potential for a significant increasein case finding of COPD-associated bronchiectasis overthe coming years.Bronchiectasis mortality rates are approximately 50 %

higher than that of uncomplicated COPD (calculated at3 % per annum) and are increasing [10]. The prognosisvaries, with a recent study of 91 patients [11] findingthat the primary cause of death was usually respiratory,with survival rates of 91 % at 4 years and 68.3 % at12.3 years. Infective exacerbations lead to significant mor-bidity. Previously published UK data also emphasise theburden of bronchiectasis, uncertainties in aetiology andlack of evidence for the treatments that are often used[12]. This is consistent with recently published Americandata on the increasing burden of bronchiectasis [13].There is no cure for bronchiectasis. Current modalities

of treatment include oral, inhaled or intravenously ad-ministered antibiotics, used both regularly and withadditional courses for exacerbations. Mucolytics andregular physiotherapy are used to aid sputum clearance,and additional guidelines for investigation, diagnosisand management of bronchiectasis have been provided bythe British Thoracic Society (BTS) [14]. Inappropriateantibiotic use can lead to antibiotic resistance. Conversely,not commencing antibiotics promptly can result in asevere exacerbation requiring costly hospital admission.Bronchiectasis differs from many chronic diseases in thatappropriate, timely recognition of symptoms and improvedmanagement of infections could lead to increased diseasestability. This could potentially lead to longer term im-provement in respiratory outcomes. For example, carryingout regular chest physiotherapy and responding appropri-ately to symptoms of exacerbation may prevent deterior-ation and reduce admissions. Patient self-care thereforecould make a significant difference to management.

In order to facilitate self-care, patients need to haveaccurate information about their condition, empoweringthem to recognise changes, respond to them and under-stand how their self-management could potentially altertheir prognosis. The BTS guidelines for the managementof bronchiectasis [14] recommend education of patientswithin their management plan. There is relatively littleinformation produced for patients with bronchiectasis.Sources include a one-page leaflet produced by the BritishLung Foundation (BLF) and limited online resources. TheBTS has a brief self-management tool for bronchiectasisthat is available to download. It does not serve as an in-formation resource but is a one-page reference guide toexacerbation management.In addition to the need for information and education

being recognised by organisations such as the BTS andthe BLF, a survey of 104 patients attending a specialistbronchiectasis clinic in the North East of England found98 % felt more confident about managing their conditionafter receiving information and education about theirtreatment [15]. A study using focus groups involving pa-tients who have bronchiectasis has highlighted lack ofinformation as one of the perceived obstacles to self-management [16]. In addition, a pilot study of qualitativeinterviews with patients identified the importance of pa-tient information in the process of developing the skillsand confidence to manage and live with bronchiectasis[17, 18]. There was a strong feeling amongst participantsthat there was a lack of trustworthy information (from areliable source such as their hospital, trusted specialistsor organisations such as the BLF) available to them be-yond that obtained in clinic. Patients felt they wouldbenefit from a credible information source that theycould continue to access outside of a specialist clinic set-ting. Despite this there remains a lack of development inthis area to date, and many chronic conditions that areless prevalent than bronchiectasis have many more access-ible resources.Our yet unpublished qualitative study used in-depth

interviews with a cohort of 26 patients and carers toidentify their unmet information needs and priorities foran information resource. We have used the themes andneeds identified during analysis of these interviews todevelop a novel patient information resource. The contentand format of the resource are based on the findings ofthe interviews and subsequent focus groups with patientsand carers to refine the intervention.A definitive, multi-centre trial would address the re-

search question: Can the provision of patient-focussedinformation and education improve health outcomes inbronchiectasis? The rationale for the Bronchiectasis Infor-mation and Education Feasibility (BRIEF) study is that, inadvance of the definitive trial, it is necessary to assesswhether the proposed design for the trial is practicable

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and will allow the proposed outcomes to be assessed. Inaddition, the intervention will be evaluated and furtherrefined for use within the definitive trial.The trial will be conducted as an unblinded, rando-

mised controlled trial comparing the use of the informa-tion resource as an intervention to usual care.

ObjectivesPrimary objectiveThe primary objective is to conduct a feasibility studythat will inform the decision of whether to proceed tothe definitive randomized controlled trial (RCT) andwhether any refinements to the design or conduct ofthat trial are warranted.

Secondary objectiveThe secondary objective is to evaluate and further refinethe patient information resource and collect informationon patient preferences.

Definitive trial objectivesThe definitive trial objectives are to assess whetherprovision of a patient-focussed information and educa-tion resource can improve patient understanding, self-management and health outcomes in bronchiectasis.

Methods/designParticipants, interventions and outcomesStudy settingThis is a single-centre study taking place in the UK inthe Newcastle upon Tyne Hospitals NHS FoundationTrust. This consists of two teaching hospital sites: theFreeman Hospital and the Royal Victoria Infirmary. Studyvisits will all take place within the Freeman Hospital. Therunning of the trial will be based within the FreemanHospital at the William Leech Clinical Trials Centre.Patients will be recruited from either hospital site.

Eligibility criteriaInclusion criteria To fulfil the inclusion criteria, theparticipant must:

1. Have the capacity to provide written informedconsent

2. Be aged 18 years or older3. Have received a clinical and radiological diagnosis of

bronchiectasis4. Be English speaking

Exclusion criteria The exclusion criteria include:

1. Cognitive impairment2. Non-English speaking3. Age <18 years

4. Participation in the preceding BronchiectasisInformation and Education (BRIE) study

Due to the nature of the study, knowledge of the Englishlanguage is a necessary inclusion criterion to ensure us-ability of the information provided. As this is a smallfeasibility study, resources are not currently available toproduce the information in other languages or to providefunded Internet access. For those potential participantswho do not have Internet access yet wish to take partin the study, the information within the website (ex-cluding video clips) can be provided in PDF format.This will be recorded on the Case Report Form(CRF), and the participant will proceed with the samevisits and outcomes.

Study intervention detailsThe BRIEF study will compare the patient informationresource (developed within the previously conducted quali-tative study) with usual care. At the baseline visit, partici-pants randomised to the intervention will receive thepatient information resource: an overview booklet andwebsite. Verbal and written instructions will be givenby appropriate members of the research team (as perthe delegation log) about how to access the website.The participants will then have access to the interven-tion for the duration of the study. Their use or not ofthe information resource will be down to individualchoice, yet through discussion with the research teammember conducting each study visit participants will beencouraged to utilise the resource and to allow theirfamilies or carers to utilise it also should they so wish.Some participants may not have direct access to a com-puter or Internet use. This does not preclude themfrom entry as long as they can access the Internet viatheir family, friends or local institutions such as librar-ies. For those who do not wish or do not have the skillsto access the website, participation using a PDF versionof the information contained within the website will beoffered. This will enable them to view all informationexcept the video clips. At study completion, those ran-domised to the intervention group will be allowed con-tinued access to the resource. Those in the controlgroup will be offered access to the resource followingcompletion of their study period so as to minimise dis-appointment due to their allocation to the control arm.Any uptake of the resource following study completiondoes not form part of data collection.This is a non-clinical intervention, and we do not ex-

pect any reasons for discontinuing the interventionother than participant preference. Any participant maychoose to leave the study at any point with no effect onusual care. Potential participants currently participating

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in another trial would not be approached for entry intothe study.

Study design and outcome measuresSee Fig. 1 and Table 1.

Design This feasibility study is an unblinded, single-centre randomised controlled trial with two parallelgroups that compares a novel patient information re-source to usual care in bronchiectasis.

Duration The study duration for each participant willbe 3 months from the study entry date. Due to variationsin month length, this will be calculated at 12 weeks

(84 days). The study completion date will be after thedate of the last assessment visit of the last entrant andcompletion of the final focus group.

Outcome measures The outcome measures are asfollows:

1. Ability to recruit adequate numbers of participants(ratio of consented participants to potentially eligibleparticipants approached)

2. Numbers completing study3. Numbers completing study scale forms,

questionnaires and visits4. Resource satisfaction questionnaire

Fig. 1 Study flow chart

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5. Recorded use of resource and alternativeinformation seeking

6. Quality of Life Questionnaire-Bronchiectasis (QOL-B)7. St George’s Respiratory Questionnaire (SGRQ)8. Hospital Anxiety and Depression Scale (HADS)9. Fatigue Impact Scale (FIS)10. Euroqol 5-dimension (quality of life scale), EQ-5D11. Number of unscheduled visits to primary or

secondary care12. Exacerbation frequency13. Forced expiratory volume in 1 second (FEV1)14. Knowledge of condition and management

questionnaire

All outcome measures will be used in assessing thefeasibility of a future definitive trial, including recruit-ment, retention and study scale form completion rates.Participant evaluation of acceptability of the newly devel-oped package will be established through a questionnaireand open questioning to include their satisfaction with theinformation provided, knowledge about their conditionand management, and additional features that they feelmay strengthen the intervention. Use of the resources pro-vided and preferred formats identified within these ques-tionnaires will also inform feasibility of a future trial andallow refinement of intervention formats. Focus groups willalso be held to strengthen data on the patient experience.Outcome measures will be recorded at baseline (day 0)

and then at 2 weeks (day 14) (that is, shortly afterinitial viewing of information in order to facilitateobtaining first opinions) and 3 months (day 84) postrecruitment. This will be done during patient visitsthat are anticipated to take less than 1 hour each.

Visit 2 can be done via telephone interview if partici-pants prefer.The time taken to complete the scales and estimates

of variability in outcome measures for the population atthe various time points, with associated confidence in-tervals, will help to inform a future sample size calcula-tion for a definitive RCT. We will describe these data asa reference for this patient group and as baseline mea-sures to inform a future RCT. We will examine the rela-tionship between outcomes and baseline covariates inorder to identify any efficacy gains through the use ofstratification in a future full RCT.EQ-5D will be used to allow some estimate of health

economic evaluation for a future RCT. We anticipatepotential health economic benefits with patients empow-ered to self-manage, thereby reducing service use. Thenumber of unscheduled presentations, exacerbation rateand FEV1 could potentially be used in a future full trialas a representation of the patients’ ability to self-managetheir condition. This information will be retrieved fromthe patient visits and patients’ symptom and informationsheets (patients will be asked to complete a monthlypostal record sheet [at weeks 4, 8 and 12] enabling iden-tification of episodes of change in symptoms and actionstaken, in addition to any information resource use, with-out the burden of a daily diary record) and also throughgeneral practitioner (GP) and hospital recorded atten-dances if patients are unable to report or recollect.

ParticipantsPotential participants will be identified by case note reviewand attendance at outpatient clinics and will be given orsent a letter of invitation to the study and a patient infor-mation sheet. Written informed consent will be obtained

Table 1 Study visits and data collection

Visit 1 Day 0 Visit 2 Week 2(Day 14)

Visit 3: final visit Week 12(Day 84)

Written informed consent and randomisation (if not done prior to visit 1)and collection of baseline demographics

x

Resource use (not baseline visit) and information seeking (x) x x

Resource satisfaction questionnaire x x

Bronchiectasis knowledge questionnaire x x x

QOL-B x x x

SGRQ x x

HADS x x x

FIS x x

EQ-5D x x x

Number of unscheduled visits x x x

Exacerbation frequency x x x

FEV1 x (if not done inpast 3 months)

x

QOL-B Quality of Life Questionnaire-Bronchiectasis, SGRQ St. George’s Respiratory Questionnaire, HADS Hospital Anxiety and Depression Scale, FIS Fatigue ImpactScale, EQ-5D Euroqol 5-dimension (quality of life scale), FEV1 forced expiratory volume in 1 second

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from willing participants (see Additional file 1). Patientscan withdraw consent at any point with no effect on usualcare. At the end of the study, some participants will be in-vited to attend a focus group and a possible in-depthinterview about their experience. For this section of thestudy only, if participants in the intervention group indi-cate that their partner/family member or friend has alsoused the resource, then they may be invited to attend dis-cussion groups also. Up to a maximum of 10 additionalparticipants will be recruited for this purpose. Additionalinformation sheets and consent forms have been producedfor these participants (see Additional file 2). Participantsinvited to attend the focus group will be sampled purpos-ively. The intent is to form a group that includes partici-pants of differing backgrounds and time since diagnosis,some from the control and some from the interventiongroup, and those who had differing preferences in termsof format used. Involvement in the focus group, however,is an optional extra, and as such a pragmatic approach willhave to be taken. Anyone agreeing to take part in thefocus group will be invited to bring along their ‘carer’, whowill then be sent the appropriate information sheet toconsider whether they would like to take part.

Participant identification and screeningPatients will be identified through case note review andclinic attendance. Eligible participants will be invited toparticipate by their consultant, the principal investigator(PI) or the chief investigator (CI), who is part of themedical team. The study will be explained to them furtherby the research team. A study Participant InformationSheet will be provided at this time, which the patient cantake away for consideration. For those identified by casenote review, a letter of invitation will be sent in the postalong with the Participant Information Sheet and detailsof how to get in touch if interested. They will be offered theopportunity to discuss this further with the research team.A screening log will be kept to document details of

subjects invited to participate in the study. For subjectswho decline participation, this will document any reasonsavailable for non-participation. The log will also ensurepotential participants are only approached once.

Sample sizeThe sample size will be 70, with a minimum of 30 beingrandomised to each arm. This is based on previous rec-ommendations for good practice in feasibility studies[19]. Because this is a feasibility study, no formal powercalculations have been carried out. Up to 10 non-patient(carer) participants will be recruited for the qualitativesection of the study, as discussed in the section ’Focusgroup data’.We anticipate that 24 months will be adequate time

to recruit 70 patients to this study, based on a clinic

attendance of approximately 60 per month with an esti-mate of 50 % of patients approached who are willingand able to enter. Seventy patients recruited from ap-proximately 140 patients approached would correspondto a 95 % confidence interval for the recruitment rateof 41–59 % (an acceptable width of ±9 %). We expectlow attrition rates based on previous work and our priorexperience in this field. There will be a 3-month additionalperiod for follow-up of the last recruited participants andtime beyond for the interviews, focus groups and analysis.

Assignment of interventionRandomisationParticipants will be randomised to intervention or con-trol in a 1:1 ratio, using random permuted blocks withinstrata. Randomisation will be stratified by gender. Therandomisation allocation schedule will be generated by astatistician with no other involvement in the study.Randomisation will be performed by the CI at site, oran individual with delegated authority, using a securepassword-protected web-based system administered byNewcastle Clinical Trials Unit. Randomisation will gen-erate a unique 3-digit study identification number foreach participant. Participants will be informed of theirallocated treatment group following randomisation.Blinding is not feasible for this study for patients or theresearch team conducting the study visits due to thenature of the intervention. The data analyst is also in-volved directly with the study processes and data col-lection, and thus blinding of the analyst is not possible.

Data collection, management and analysisData collectionData will be collected at study visits by the researchteam as per the delegation log. Visits 1 and 3 will bedone in person; visit 2 can be either in person or on thetelephone. Other than breathing tests at visits 1 and 3,all outcome measures are questionnaires and will be ei-ther self-completed by the participants or completedwith the help of the research team member conductingthe study visit. All answers will be recorded in papercopies of each questionnaire within the CRF. The studyteam member conducting the visit will check for omis-sions after completion with the participant. All membersof the delegate log will be trained in the use of the ques-tionnaires and lung function tests. The questionnaires tobe completed are summarised in Table 2. Additionaldata collection will be obtained via monthly (weeks 4, 8,12) postal symptom and resource use record sheets sentto participants. This will enable more accurate recollec-tion of symptoms and information use than at the studyvisits alone, yet is a reduction in burden as compared tocompleting a daily diary. Phone calls will be made to en-courage completion if the forms are not returned.

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Focus group dataA number of participants will be invited to a focus groupto discuss participation in the trial and views on furtherrefinements to the intervention and the study protocol.Should specific issues arise within the focus groups thatneed further exploration, then a number of in-depth in-terviews may also be held. These would be entirely op-tional. If participants indicate that their partner, familymember or friend has used the resource, then they maybe invited to this section of the study also. A maximumof 10 carers will be recruited and given the appropriateParticipant Information Sheet, and written informedconsent will be obtained. Thematic analysis will be usedto look for patterns of meaning and ‘themes’ in the datacontent. Data will be organised into meaningful groupsto identify and describe themes and issues raised in theinterviews.

Data handling and record keepingData collected on paper CRFs will be entered by the CIor appropriately trained study delivery staff and data man-ager (as per the delegation log) on a secure password-protected study computer. Participants will be identifiableonly by a unique study identifier on all recorded data.Focus group audio files will be transcribed verbatim.

All data will be stripped of strong identifiers and willonly be identified by a unique study number, and onlyauthorised members of the research team, operating towritten codes of confidentiality, will have access to thelink between anonymised data and patient/professional

identifiable details. Patients and professionals will not beidentifiable in any publications emanating from the workdescribed in this application. Data will be handled, com-puterised and stored in accordance with the Data Pro-tection Act 1998. No participant identifiable data willleave the study site.

Compliance and withdrawalCompliance Where feasible, study visits will coincidewith routine clinical follow-up to enhance the likelihoodof good compliance. Visit windows of 2 weeks shouldensure visit attendance; non-attendance for study visitswill prompt follow-up by telephone. Participants will begiven the option of completing visit 2 by telephoneinterview to reduce the burden of travel for study visits.Non-return of monthly postal record sheets will alsoprompt follow-up by telephone.

Withdrawal of participants Participants have the rightto withdraw from the study at any time for any reasonand without giving a reason. The investigator also hasthe right to withdraw patients from the study interven-tion if she/he judges this to be in the patient’s best inter-ests. It is understood by all concerned that an excessiverate of withdrawals can render the study uninterpretable;therefore, unnecessary withdrawal of patients should beavoided. Should a patient decide to withdraw from thestudy, all efforts will be made to report the reason forwithdrawal as thoroughly as possible.There are two withdrawal options:

1. Withdrawing completely (withdrawal from both thestudy intervention and provision of follow-up data)

2. Withdrawing partially (withdrawal from the studyintervention but continuing to provide follow-updata by attending clinic and completingquestionnaires)

Consent will be sought from participants choosingoption 1 to retain data collected up to the point ofwithdrawal. Participants will be asked if they wouldallow the reason for the decision to withdraw to berecorded.

Statistical analysisA statistical analysis will be performed using SPSS 17.0.As this is a feasibility study, the analyses of the data col-lected will be mainly descriptive, with 95 % confidenceintervals reported where appropriate. As a randomisedcontrolled trial, the primary analysis will be based on theintention-to-treat principle with analysis groups basedon the groups allocated at randomisation and all rando-mised patients being included in the analysis. As a feasi-bility study, the extent of missing data will be assessed

Table 2 Outcome measures

Study instrument Description

Resource use andinformation seeking

Unvalidated questionnaire

Resource satisfactionquestionnaire

Unvalidated questionnaire

Bronchiectasis knowledgequestionnaire

Unvalidated questionnaire

QOL-B Validated Quality of Life Questionnaire-Bronchiectasis [26]

SGRQ Validated St George’s RespiratoryQuestionnaire [3]

HADS Validated Hospital Anxiety and DepressionScale [27]

FIS Validated Fatigue Impact Scale [28]

EQ-5D Validated Euroqol 5-dimension quality oflife questionnaire [29]

Number of unscheduledvisits

Patient’s report of healthcare visits

Exacerbation frequency Patient’s report of number ofexacerbations

FEV1 (absolute value and% predicted)

Lung function test (forced expiratoryvolume) using calibrated equipment

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and reported, and analysis of outcomes may also becarried out on a complete-case basis. Rates will be cal-culated as defined and reported with 95 % confidenceintervals. At baseline and by intervention group thedistribution of all numerical variables will be examinedand summarised using measures of location and spread.Similarly, baseline categorical variables will be tabulatedand percentages reported. Change in the questionnaireoutcomes from baseline to 2 weeks and 3 months will besummarised. The difference in the mean change betweenthe intervention groups from baseline to each of the twotime points will be explored for all outcome measures andreported with accompanying 95 % confidence intervals.Such results will be interpreted cautiously because ofthe size of the study and the possible imbalance in pre-randomisation baseline covariates. The relationship be-tween baseline covariates and outcome measures willbe examined graphically and quantified appropriatelydepending on their distribution. No formal statisticaltesting will be performed. Confidence limits for the es-timated standard deviations of key study parameterswill be calculated and used in sensitivity analyses forsample size calculations for a future definitive RCT.

MonitoringThis is a low risk trial, and major safety data are notanticipated. As agreed upon by Newcastle upon TyneHospitals, the Trial Oversight Committee (TOC) willadopt the joint roles of Trial Steering Committee (TSC)and Data Monitoring and Ethics Committee (DMEC) withindependent members meeting in closed session to fulfilthe DMEC role. The TOC comprises an independentchair, an independent consumer representative, a patientrepresentative, a carer representative, CI, PI, data managerand statistician. The TOC will meet bi-annually. Their roleis to monitor progress and supervise the trial to ensure itis conducted to high standards in accordance with theprotocol, the principles of good clinical practice (GCP)and relevant regulations and guidelines and with regard toparticipant safety. The purpose of this committee will beto monitor study progress and patient safety. Monitoringof study conduct and data collected will be performed bysite review to ensure the study is conducted in accordancewith GCP. The main areas of focus will include consent,serious adverse events and essential documents in study.The study may be subject to inspection and audit by

Newcastle upon Tyne Hospitals under their remit assponsor and by other regulatory bodies to ensure adher-ence to GCP. The investigator(s)/institutions will permittrial-related monitoring, audits, Research Ethics Commit-tee (REC) review and regulatory inspection(s), providingdirect access to source data/documents.There is no interim analysis planned for this study.

Adverse event monitoring and reportingDefinitionsAdverse event (AE) An AE is an untoward medical oc-currence in a subject to whom a study intervention orprocedure has been administered, including occurrenceswhich are not necessarily caused by or related to thatintervention. An AE, therefore, does not necessarily havea causal relationship with the treatment. In this context,‘treatment’ includes all interventions (including compara-tive agents) administered during the course of the study.Medical conditions/diseases present before starting studytreatment are only considered AEs if they worsen afterstarting study treatment.

Related adverse event A related AE is one that resultsfrom administration of any of the research study proce-dures. All AEs judged by either the reporting investigatoror the sponsor as having reasonable causal relationship toa study procedure qualify as ‘related adverse events’. Theexpression ‘reasonable causal relationship’ means toconvey in general that there is evidence or argument tosuggest a causal relationship.

Causality The assignment of the causality should bemade by the investigator responsible for the care of theparticipant using the definitions in Table 3. All AEsjudged as having a reasonable suspected causal relation-ship to a study procedure (that is, definitely, probably orpossibly related) are considered to be related AEs. If anydoubt about the causality exists, the local investigator(PI) should inform the CI. In the case of discrepant

Table 3 Definitions of causality

Relationship Description

Unrelated There is no evidence of any causal relationship

Unlikely There is little evidence to suggest there is acausal relationship (e.g. the event did notoccur within a reasonable time afteradministration of the study procedure). Thereis another reasonable explanation for the event(e.g. the participant’s clinical condition or otherconcomitant treatment)

Possible There is some evidence to suggest a causalrelationship (e.g. because the event occurswithin a reasonable time after administrationof the study procedure). However, theinfluence of other factors may have contributedto the event (e.g. the participant’s clinicalcondition or otherconcomitant treatments)

Probable There is evidence to suggest a causal relationshipand the influence of other factors is unlikely

Definitely There is clear evidence to suggest a causalrelationship and other possible contributingfactors can be ruled out

Not assessable There is insufficient or incomplete evidence tomake a clinical judgement of the causal relationship

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views on causality between the investigator and others,all parties will discuss the case. In the event that noagreement is made, the main REC and other bodies willbe informed of both points of view.

Unexpected adverse eventAn unexpected AE is one that is not listed in the studyprotocol as an expected occurrence in the circumstancesof this trial.

Serious adverse event (SAE)An SAE is an untoward occurrence (whether expectedor not) that:

� Results in death� Is life-threatening (refers to an event in which the

subject was at risk of death at the time of the event;it does not refer to an event which hypotheticallymight have caused death if it were more severe)

� Requires hospitalisation or prolongation of existinghospitalisation

� Results in persistent or significant disability orincapacity

� Consists of a congenital anomaly or birth defect� Is otherwise considered medically significant by the

investigator

Medical judgement should be exercised in decidingwhether an AE is serious in other situations. Importantmedical events that are not immediately life-threateningor do not result in death or hospitalisation but may jeop-ardise the patient or may require intervention to preventone of the other outcomes listed in the definition aboveshould also be considered serious.

Severity (intensity) of adverse events and adverse reactionsThe severity of all AEs will be graded on a three-pointscale of intensity (mild, moderate and severe):

� Mild: Discomfort is noticed, but there is nodisruption of normal daily activities.

� Moderate: Discomfort is sufficient to reduce oraffect normal daily activities.

� Severe: Discomfort is incapacitating, resulting ininability to work or to perform normal daily activities.

An AE may be severe but not serious.

Expected adverse reactionsThis is a low risk study, and there are no expected ad-verse reactions (ARs) from the intervention as it is aninformation resource rather than a treatment. Studyprocedures in the main are completing forms. Very oc-casionally when people perform spirometry (which will

be measured at study visits) they may feel light headedfor a short while afterwards. Spirometry tests will be per-formed seated, and if participants have a known tendency,this test will be omitted. As this is a rare but expected AR,it would not be reported. Only suspected unexpectedserious adverse reactions (SUSARs) will be reported.

Recording and reporting adverse events or reactionsAll AEs should be reported as per protocol specifications.Depending on the nature of the event, the reportingprocedures in the succeeding paragraphs should befollowed. Any questions concerning AE reporting shouldbe directed to the CI or PI in the first instance.

Adverse eventsAll non-serious AEs during study participation will bereported on the study CRF and sent to the CI within2 weeks of the form being due. Severity of AEs will begraded on a three-point scale (mild, moderate and severe).Relation (causality) and seriousness of the AE to the treat-ment should be assessed by the investigator at site in thefirst instance. The individual investigator will be respon-sible for managing all AEs according to local policy.

Serious adverse eventsAll SAEs during study participation shall be reported tothe CI within 24 hours of the site learning of its occur-rence. The initial report can be made by telephone oremail. Use of the SOHO66 fax system ensures that theNCTU, sponsor and CI are all informed by emailsimultaneously.In the case of incomplete information at the time of

initial reporting, all appropriate information should beprovided as follow-up as soon as it becomes available.The relationship of the SAE to study procedures shouldbe assessed by the investigator at site, as should the ex-pected or unexpected nature of the SAE.

Ethics and disseminationEthics and regulatory issuesThe conduct of this study will be in accordance with therecommendations for physicians involved in research onhuman subjects adopted by the 18th World MedicalAssembly, Helsinki, 1964 and later revisions.Favourable ethical opinion from NRES Committee

North East - Sunderland (reference 14/NE/0119) hasbeen granted, and R&D approval (reference 7005) fromthe Newcastle upon Tyne Hospitals NHS FoundationTrust was granted prior to commencement of the study.Any protocol amendments will be approved by R&Dand the Sunderland REC and will be communicated toall relevant parties: investigators, registries, participants.

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Information sheets will be provided to all eligible sub-jects and written informed consent obtained prior to anystudy procedures.

Informed consent proceduresInformed consent discussions will be undertaken by ap-propriately trained site staff (as per the delegation log)involved in the study, including medical staff and researchnurses, with the opportunity for participants to ask anyquestions. Following receipt of information about thestudy, participants will be given reasonable time (aimingfor a minimum of 24 hours) to decide whether or not theywould like to participate. Those wishing to take part willprovide written informed consent by signing and datingthe study consent form, which will be witnessed and datedby a member of the research team with documented, dele-gated responsibility to do so. Written informed consentwill always be obtained prior to randomisation and priorto study-specific procedures/investigations.The original signed consent form will be retained in

the Investigator Site File, with a copy in the clinical notesand a copy provided to the participant. The participantwill specifically consent to his/her GP being informed oftheir participation in the study.The right to refuse to participate without giving reasons

will be respected.Due to the small subject population and the inclusion

criteria, the information sheet and consent form for thestudy will be available only in English.

ConfidentialityPersonal data will be regarded as strictly confidential.To preserve anonymity, any data leaving the site willidentify participants by their initials and a unique studyidentification code only. The study will comply with theData Protection Act 1998. All study records and Inves-tigator Site Files will be kept at site in a locked filingcabinet with restricted access. Only members of the re-search team will have access to the final dataset and ac-cess as required for necessary audit and monitoring.

Insurance and financeThe sponsor, the Newcastle upon Tyne Hospitals NHSFoundation Trust, has liability for clinical negligencethat harms individuals toward whom they have a duty ofcare. NHS indemnity covers NHS staff and medical aca-demic staff with honorary contracts conducting the trialfor potential liability in respect of negligent harm arisingfrom the conduct of the study. The Newcastle uponTyne Hospitals NHS Trust is sponsor and, through thesponsor, NHS indemnity is provided in respect of po-tential liability and negligent harm arising from studymanagement. Indemnity in respect of potential liabilityarising from negligent harm related to study design is

provided by NHS schemes for those protocol authorswho have their substantive contracts of employmentwith the NHS and by Newcastle University insuranceschemes for those protocol authors who have their sub-stantive contract of employment with the university.This is a non-commercial study, and there are no arrange-ments for non-negligent compensation. Newcastle Univer-sity provides insurance coverage for the trial design.The National Institute for Health Research (NIHR) is

funding the study through a doctoral research fellowshipawarded to the CI.

Study reporting and publicationsIt is planned to publish this study in peer-reviewed arti-cles and to present data at national and internationalmeetings. Results of the study will also be reported tothe sponsor (Newcastle upon Tyne Hospitals) and funder(NIHR) and will be available on their websites. All manu-scripts, abstracts or other modes of presentation will bereviewed by the Trial Overview Committee and funderprior to submission. This will also form part of the PhDthesis of the CI. Individuals will not be identified from anystudy report. Participants will be informed about theircontribution to the study, including a lay summary of theresults, at the end of the study.

DiscussionThis study is a low risk study. As the study and inter-vention have been co-developed with potential users,we hope this will make the trial process and use of theresource straightforward and beneficial. The study willboth inform a future multi-centre trial and allow forevaluation and refinement of the patient informationresource to maximise potential future uptake and impact.Analysis of outcome measures will begin to determineimpact of this novel information resource on patientknowledge and confidence to self-manage and informdevelopment of a definitive trial to determine the effecton disease stability.The relatively short duration of the feasibility study

may limit the usefulness of exacerbation frequency datain terms of defining this rate for a definitive trial. Weare collecting these data to determine the feasibility oftheir use as an outcome measure, yet for a definitive trialwith a longer follow-up period, it is likely that we wouldneed to refer to previously published rates of exacerba-tion frequency in bronchiectasis. Within a recent ana-lysis of 155 patients at our centre this was found to beroughly 4 per annum [20], although this does differ be-tween publications as outlined in the BTS guidelines forthe treatment of bronchiectasis [14]. It has also beendemonstrated that exacerbation rates vary seasonally[21], and with a shorter feasibility study frequency istherefore harder to extrapolate accurately. Additionally,

Hester et al. Trials (2016) 17:210 Page 10 of 12

in terms of reporting of exacerbations, within this studydesign we have relied upon patient reporting of numbersof exacerbations for which they have required treatmentwith a course of antibiotics. We have not included astrict definition of an exacerbation within the protocolas we have not asked patients to report changes insymptoms in real time nor made decisions about diagno-sis of exacerbations or treatment for them. We do notanticipate a significant problem with ascertainment bias,yet consideration of this will also help to inform the de-finitive trial. Due to the short amount of time betweenvisits in this study, we do not anticipate issues with re-call, although patient notes can be used as an alternativemechanism.One of the potential impacts of the intervention will

be to improve symptom recognition and management.This will not, however, be a uniform change. Some par-ticipants were likely to have under-recognised exacer-bations prior to study participation, and others werepossibly taking courses of antibiotics for symptoms theyfelt were indicative of an exacerbation that were in factjust ‘normal’ variations in their chronic symptoms. Thus,using number of courses of antibiotics or change innumber is not necessarily a useful measure; hence theadditional recording of unscheduled healthcare usage.The addition of qualitative data through the use of

focus groups will allow for a richer exploration of theexperience of both the trial process and use of the infor-mation package for participants. Although we know thatpatients want more information about bronchiectasis[17], it is argued that health information alone doesnot necessarily produce changes in behaviour [22]. How-ever, asthma studies have shown that delivering educationabout the key aspects of the condition, allowing patientsto acquire skills, and education in combination withclinical review and action plans can lead to demonstrableimprovements [23–25]. By providing improved educa-tional interventions that meet the needs of patients withbronchiectasis and their carers, we aim to facilitate im-provements in self-management. Our aim is that inaddition to providing a resource that is a reassuringsource of support for patients and carers, improve-ments in understanding and management will lead toimprovements in health outcomes and healthcare ser-vice use longer term. By evaluating and refining thispatient-driven intervention and assessing the feasibilityof conducting a future definitive RCT, we are makingimportant progress in the provision of much needed in-terventions in bronchiectasis.

Trial statusThe study is still recruiting at time of submission. Thefirst recruit was on 10/6/2014.

Additional files

Additional file 1: Patient consent form. (DOC 103 kb)

Additional file 2: Carer consent form. (DOC 102 kb)

AbbreviationsAE: adverse event; AR: adverse reaction; CI: Chief Investigator; CRF: CaseReport Form; DMEC: Data Monitoring and Ethics Committee; EQ-5D: Euroqol5-dimension (quality of life scale); FEV1: forced expiratory volume in 1 second;FIS: Fatigue Impact Scale; GCP: Good Clinical Practice; HADS: Hospital Anxietyand Depression Scale; MREC: Main Research Ethics Committee;NCTU: Newcastle Clinical Trials Unit; NIHR: National Institute for Health Research;NUTH: Newcastle upon Tyne Hospitals; PI: Principal Investigator (at each site);QOL-B: Quality of Life Questionnaire-Bronchiectasis; R&D: research anddevelopment; RCT: randomised controlled trial; SAE: serious adverse event;SGRQ: St George’s Respiratory Questionnaire; SUSAR: suspected unexpectedserious adverse reaction; TOC: Trial Oversight Committee; UP: unscheduledpresentation to primary or secondary care.

Competing interestsThere are no known competing interests for any of the authors. KH is fundedby a National Institute for Health Research Doctoral Research Fellowship.This article presents independent research funded by the National Institutefor Health Research (NIHR). The views expressed are those of the author(s)and not necessarily those of the NHS, the NIHR or the Department of Health.ADS acknowledges funding to the BronchUK network from the UK MedicalResearch Council (grant MR/L011263/1) and a prior Higher Education FundingCouncil (HFCE senior lectureship).

Authors’ contributionsKH conceived of the study and its design and coordination and developedthe intervention used. KH drafted the manuscript and is primary author ofthis work, which forms part of her current PhD thesis. ADS supervised andcontributed to concept, design and coordination of the study and theintervention used. ADS participated in and contributed to the manuscriptpreparation. TR contributed to the concept and design of the study and theintervention and manuscript preparation. JN contributed to the conceptand design of the study and the intervention and manuscript preparation.All authors read and approved the final manuscript.

AcknowledgementsWe would like to acknowledge Dr Vicky Ryan for advice about the statisticalanalysis plan. We would like to acknowledge research nurses Gareth Daviesand Geraldine Jones for their contribution to recruitment and study visits.We are grateful to the National Institute for Health Research for funding thiswork through a National Institute for Health Research Doctoral ResearchFellowship Award (DRF-2012-05-149) awarded to Dr Katy Hester.The sponsor of this work is the Newcastle upon Tyne Hospitals NHSFoundation Trust R&D (reference 7005).

Author details1Institute of Cellular Medicine, Newcastle University, Newcastle upon TyneNE2 4HH, UK. 2Faculty of Medical Sciences, Newcastle University, Newcastleupon Tyne NE2 4HH, UK. 3Institute of Health and Society, NewcastleUniversity, Newcastle upon Tyne NE2 4AX, UK. 4Adult Bronchiectasis service,Freeman Hospital, Newcastle Upon Tyne NE7 7DN, UK.

Received: 3 February 2016 Accepted: 7 April 2016

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