Meeting Report: Core outcome set for Venous leg ulceration CoreVen

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1 Sciece, Practice ad Educatio Meetig Report: Core outcome set for Veous leg ulceratio CoreVe Sarah Hallas 1 Adrea Nelso 1 Report from CoreVe meetig i Amsterdam 4 May 2017 INTRODUCTION The Core outcome set for Veous leg ulceratio (CoreVe) project was established i 2016 ad is registered o the COMET database ( comet-iitiative.org/studies/details/680). The project aims to develop a miimum list of outcomes o the effectiveess of itervetios used i veous leg ulceratio (VLU) ad their associated measuremet istrumets for reportig i cliical trials. The pricipal ivestigators are Prof. Adrea Nelso (Uiversity of Leeds, UK) ad Dr Georgia Gethi (NUI Galway, Irelad). Sarah Hallas is a PhD studet o the project, ad Mary Burke is a MSc Studet. Supervisio of these studets is provided by Dr Susa O Meara (Uiversity of Leeds), Prof. Adrea Nelso, ad Dr Georgia Gethi. The steerig group represets a rage of disciplies from multiple Europea coutries: Dr Ua Adderley (Lecturer ad Researcher i Commuity Nursig, Uiversity of Leeds, UK), Dr Ja Kotter (Scietific Director of Cliical Research for Hair ad Ski Sciece, Departmet of Dermatology ad Allergy, Charite-Uiversitatsmedizi Berli, Berli, Germay), Dr Mary Madde (Lecturer ad Researcher i Applied Health Research, Uiversity of Leeds, UK), Dr Paulie Meskell (Seior lecturer ad researcher at the Nursig ad Health Research Departmet, Uiversity of Limerick, Irelad), Prof. Jae Nixo (Deputy Director Istitute Cliical Trials Research, Uiversity of Leeds, UK), Dr Aoghus O Loughli (Cosultat Edocriologist, Bos Secours Hospital, Galway, Irelad ad a Alliace for Research ad Iovatio i Wouds Steerig Committee Member), Prof. Sebastia Probst (Professor of Tissue Viability ad Woud Care, Uiversity of Applied Scieces Wester Switzerlad, Geeva, Switzerlad ad Coucil Member ad Editor, EWMA), Mr Wael Tawfick (Vascular Surgeo Saolta Uiversity Health Care Group, Uiversity Hospital Galway, ad the School of Medicie, Natioal Uiversity of Irelad Galway, Irelad, ad a Alliace for Research ad Iovatio i Wouds Steerig Committee Member), ad Dr Thomas Wild (Geeral Surgeo, specialisig i woud maagemet ad septic surgery, Uiversity Medical Ceter Hamburg-Eppedorf, Germay ad Editor-i-Chief, Woud Medicie). AIMS OF THE MEETING The aim of the meetig was to itroduce the project, its ratioale, its purpose, ad progress to date as well as to gai feedback o the proposed methodology. The project team members are grateful to the EWMA for facilitatig this first ope meetig. ATTENDANCE AT THE MEETING Notificatio of the meetig was provided i the coferece programme ad o the website ad was therefore ope to all delegates. Key opiio leaders i VLU maagemet who were attedig the coferece were iformed of the meetig, ad pre-coferece otificatios were set to cotacts. A total of 52 people atteded the meetig from various backgrouds, which icluded patiet orgaisatio represetatives, vascular surgeos, Susa O Meara 1 Georgia Gethi 2,3 1 School of Healthcare, Uiversity of Leeds, Leeds, UK 2 School of Nursig ad Midwifery, Natioal Uiversity of Irelad Galway, Galway, Irelad 3 Alliace for Research ad Iovatio i Wouds Correspodece: hc11s4h@leeds.ac.uk Coflicts of iterest: Noe EWMA Joural 2017 vol 18 o 2 27

2 physicias, dermatologists, podiatrists, urses, sociologists, ad researchers. BACKGROUND A core outcome set (COS) is a miimum set of outcomes that should be measured ad reported i all cliical trials for a specific cliical area as agreed o by stakeholders i that field 1. A outcome is ay idetifiable cosequece of the exposure to a health care itervetio, such as a drug or a dressig. A outcome must be appropriate, measurable, ad meaigful to stakeholders. COS are gaiig recogitio as a meas of improvig the potetial for metaaalysis withi systematic reviews ad ultimately sythesisig results of trials that iclude outcomes of importace to patiets ad key stakeholders. A COS also reduces the risk of outcome-reportig bias 2. For example, i the absece of these miimum requiremets, the presetatio of fidigs may be limited to outcomes with statistically sigificat results. The implemetatio of the COS for VLUs by researchers will icrease the utility of trials i this field ad facilitate compariso amogst differet sources of evidece. May areas of healthcare have developed a COS, such as the Outcome Measures i Rheumatology (OMERACT; 3 ), the maagemet of Otitis Media with Effusio i childre with cleft palate (momet; 4 ), ad Harmoizig Outcome Measures for Eczema (HOME; 5 ). To date, however, o stadardised methods of assessmet or COS exist for VLU maagemet, ad three previous systematic reviews have idetified the diversity of outcomes i RCTs i this field 6,7,8. A recet qualitative study 9 that aimed to idetify the most importat outcomes for complex wouds from the perspectives of patiets, carers, ad healthcare professioals foud that most patiets with VLUs, icludig itraveous drug users, ad healthcare professioals ivolved i their care regarded the healig of the woud as the primary treatmet goal. Patiets were greatly troubled by the social cosequeces of havig a complex woud. Thus, the CoreVe project team is workig together to develop a miimum list of outcomes for VLU trials. A VLU is a chroic woud that occurs below the kee ad takes more tha six weeks to heal 9. A VLU is a chroic ad reoccurrig coditio 11 that is caused by impaired veous blood flow triggered by veous hypertesio. The prevalece of VLUs has bee estimated at 0.29 per 1000 idividuals i the UK (95% cofidece iterval ) 12. Estimates i the Wester world suggest that 1% of the populatio experiece VLUs, ad this rate could be as high as 3% i people over the age of 65 years 13. Veous hypertesio results i damage to the valves i the legs, allowig two-way blood flow to occur istead of the ormal oe-way flow of blood ad resultig i swellig of the leg veis, oedema, ad leakage of circulatory fluid ito the surroudig tissue from the capillaries i the lower legs 14. VLU ca result i pai, malodour, susceptibility to ifectio, ad lack of mobility 15. These issues, i tur, affects the patiet s quality of life through reductio i social activity, limits o their capacity to work, ad iability to perform self-care ad persoal hygiee activities 9,16. I order to esure idividuals receive good quality care ad treatmet supported by evidece-based practice, effective treatmets must be developed ad rigorously tested. The lack of cosistecy i cliical trial outcomes meas that it is difficult to compare results of cliical trials or to perform meta-aalysis 6. This lack of cosistecy limits cliical judgmets, as trials ofte have umerous ad differet outcomes. Ofte the choice of outcomes is ot carefully cosidered as may of the outcomes are ot regarded as importat by patiets. The use of these outcomes i cliical trials has led to waste i study resources ad reportig, ad these issues may be avoidable with the use of a COS 2. Aother challege is that differet trials use differet measuremet istrumets at differet time poits ad ofte with little referece to the validity ad reliability of such istrumets 6. These issues uderscore the eed to develop COS ad appropriate measuremet istrumets for cliical trials for VLU treatmet. While o sigle method of developig a COS is accepted, a multi-stage process i which all stakeholders, icludig patiets ad their carers, cotribute to the fial outcome set will be the most useful. Firstly, a core domai set is established. This step is followed by developmet of a cosesus miimal set of outcomes that should be reported for ay trial. Fially, cosesus o how the outcomes are to be measured with respect to validity ad reliability of the measuremet istrumets is achieved amogst the participatig stakeholders. DEVELOPMENT OF COS IDENTIFICATION OF POTENTIAL OUTCOMES Scopig review The results of a scopig review, which icluded all outcomes idetified i the Cochrae Systematic Review database that icluded RCTs i patiets with VLU, were preseted at the meetig. A scopig review eabled the cocepts i a field of iterest to be mapped out 17 ad allowed for a rapid uderpiig of the key cocepts 18. The adaptatio of the Arksey ad O Malley 17 five-stage methodological framework for coductig a scopig review by Levac et al. 19 was used to guide the review. Stage 1 idetified the research questio, which although broad, still icludes the study populatio. I this case, the study 28 EWMA Joural 2017 vol 18 o 2

3 Sciece, Practice ad Educatio populatio icluded people with VLUs. Stage 2 idetified the relevat studies, which were RCTs icluded i the Cochrae systematic reviews. Stage 3 defies the study selectio. Levac et al 19 recommeded that the iclusio ad exclusio criteria ca be applied post hoc as the researcher becomes icreasigly familiar with the literature. The chartig of the data (Stage 4) was desiged accordig to the framework aalysis of Ritchie ad Specer 20. I this stage, the outcomes were orgaised ito a structured table that facilitated the groupig of the outcomes ito domais. The results were collated, summarised, ad reported i Stage 5. I total, 807 (post-deduplicatio) potetial outcomes were extracted. Through cosesus amogst the group members, these 807 outcomes were grouped ito 11 domais (Table) ad preseted at the meetig. Domais are broad, descriptive categories that host potetial groupigs of several, more specific, outcomes. Table: Domais idetified followig the scopig review. Healig Patiet-reported symptoms Cliicia-reported symptoms Carer-reported symptoms Life impacts Cliical sigs Cliical measuremet Performace of the itervetio Resource use: supplies Resource use: cliicia time Adverse evets CONSENSUS METHODS DISCUSSION The method to be used to gai cosesus from stakeholders was opely discussed at the EWMA meetig. The followig topics were itroduced, ad agreemet was achieved. Stakeholders will iclude patiets, carers, health professioals, policy makers, researchers, ad idustry represetatives. Two members (Nelso ad O Meara) of the project team are editors for Cochrae Wouds Group (CWG), esurig the ivolvemet of a broad rage of stakeholders. Other steerig group members also have expertise i Cochrae Reviews. We are also likely to cotact additioal people who cotribute to the CWG (e.g., review authors ad editors) through the proposed etworks. The Delphi method will be used via a olie survey tool (Bristol Olie Survey) to gai cosesus o the domais. Participats will be asked to rate each domai i terms of importace o a Likert scale of 1 to 9 (1 beig ot importat, ad 9 beig extremely importat). Discussio with the audiece suggested that most people were i favour of icludig two rouds for each step of the cosesus process. The ratioale behid this is that it is methodologically defesible. That is, with two rouds, we will be able to better idetify ad uderstad the complexities of the decisio process, i agreemet with processes for other COS21. A audiece member highlighted the fact that a olie format has methodological limitatios ad may be limited i its ability to reach the patiet group. This challege was discussed ad ackowledged by the team. Because of fudig restraits, however, it will ot be possible to sed out paper copies of the survey. Paper formats are also much more time cosumig. The survey will beefit from the sowball effect, i that the umber of people that have the opportuity to participate will be icreased via liks from woud care orgaisatios ad all other kow etworks with a iterest i VLU research; however, idividuals will ot be cotacted by their Natioal Health Service (NHS) UK use or employmet. Ethical approval for this step has bee sought from the Uiversity of Leeds, UK. It was suggested that ulcer recurrece should be cosidered a outcome. The iitial respose from the team was that ulcer recurrece was ot icluded i this COS iitiative, as the focus of the COS was the treatmet of ope VLUs. Followig a i-depth discussio, the group cocluded that ulcer recurrece will ot be icluded as a domai or outcome. Ufortuately, the scope of this project caot cover all aspects of VLU maagemet, especially i light of the fact that the scopig review of ope ulceratio has revealed that this by itself is a sigificat edeavour. A audiece member asked whether there will be represetatio from the healthcare idustry. Followig a i-depth discussio after the meetig at EWMA, it was decided that healthcare idustry represetatives will be part of the stakeholder group. Additioal issues that will ot be addressed withi the scope of the project were addressed. The CoreVe project aims to develop the COS oly ad will ot be advisig o the coduct ad reportig of trials; however, we highlight the eed for future research o the coduct ad reportig i VLU trials. The followig issues were discussed: EWMA Joural 2017 vol 18 o 2 29

4 The idea that the COS should iclude recommedatios about duratio of follow-up was suggested. This idea was discussed based o the criticisms raised i the systematic review by Hodgso et al. 22, i which a media follow-up of 12 weeks was suggested for trials evaluatig treatmets for chroic wouds. A later commet reiterated that recommedatio for a miimum follow-up time for assessmet of both healig ad recurrece withi that period would be useful. Our group, however, will ot be recommedig a miimum followup time; however, we do emphasise that future research o the miimum follow-up time is eeded. Members of the audiece suggested that trials should report baselie progostic variables per group. While the COS will ot cover such recommedatios, the COS, oce established, ca be implemeted alogside tools, such as CONSORT (Cosolidated Stadards of Reportig Trials, 23), which icludes recommedatios o the reportig of baselie variables, to address this issue. A questio was posed regardig whether the COS would provide guidace o the target umber of trial participats. The team respoded by statig the COS will recommed outcomes o which estimatios of statistical power would be based but would ot recommed a target umber for trial participats directly as this umber depeds o the idividual trial aims. Members of the audiece questioed how the steerig group decided o a 70% level of cosesus (as opposed to other values). The team respoded that this decisio was based o methods used by other COS iitiatives, such as OMERACT 24, which developed COS i rheumatology; Kirkham et al. 25, who developed the COS- STAR (Core Outcome Set-STAdards for Reportig) statemet; McNair et al. 26, who developed COS i colorectal cacer surgery; ad Millar et al. 21, who developed COS i prescribig for older adults i care homes. The core outcome(s) may vary accordig to trial edpoit ad the treatmet beig evaluated. The team respoded to this poit by statig that the aim of the iitiative is to idetify core outcomes for all VLU trials ad that trialists ca certaily add other outcomes. The core outcome may be a secodary outcome withi a study ad does ot ecessarily have to be a primary outcome. A audiece member also said that researchers ivolved i future studies should be able to justify the reasos that outcomes from the COS were ot reported i the trial. CONCLUSION The meetig was successful as the audiece raised valuable questios ad provided helpful commets durig the meetig to facilitate the developmet of the COS. I coclusio, idustry stakeholders will be accessed through their idetified etworks. Researchers will be able to iclude additioal outcomes i their studies, will be able to decide which of the COS are primary ad secodary i their trials, ad will be able to omit some outcomes as log as they provide justificatio. As with all iitiatives, some issues will ot be covered by the scope of the project because the CoreVe project aims to develop the COS oly ad will ot be advisig o the coduct ad reportig of trials. The team, however, emphasises the eed for future research o coduct ad reportig i VLU trials. This icludes recommedatios o the miimum follow-up time, baselie progostic variables, ad umber of trial participats. A two roud olie survey that will soo be lauched will seek to gai cosesus o the domais listed (see Table). Followig this survey which is to gai cosesus o the domais, a additioal olie survey will be completed i two rouds to gai cosesus o the specific outcomes that fall withi the domais that were voted as importat i the previous olie survey. WHAT IS NEXT? The olie survey will be lauched i September/October 2017, ad the team aims to complete the two rouds of data gatherig by December The fidigs will be ready for presetatio i early A secod meetig will be held i 2018 to discuss the fidigs ad fialise the method for the secod Delphi study o the core outcomes. The full protocol will be published ad made readily available. You ca cotact us: Sarah Hallas via hc11s4h@leeds.ac.uk Nostadard abbreviatios CONSORT Cosolidated Stadards of Reportig Trials CoreVe Core outcome set for Veous leg ulceratio COS Core Outcome Set COS-STAR Core Outcome Set- STAdards for Reportig CWG Cochrae Wouds Group EWMA Europea Woud Maagemet Associatio HOME Harmoizig Outcome Measures for Eczema momet maagemet of Otitis Media with Effusio i childre with cleft palate NHS Natioal Health Service OMERACT Outcome Measures i Rheumatology RCT Radomised Cotrol Trial VLU Veous Leg Ulceratio 30 EWMA Joural 2017 vol 18 o 2

5 Sciece, Practice ad Educatio STEERING GROUP: Dr Ua Adderley 1 Dr Ja Kotter 5 Dr Mary Madde 1 Dr Paulie Meskell 6 Prof. Jae Nixo 4 Dr Aoghus O Loughli 3,7 Prof. Sebastia Probst 8 Mr Wael Tawfick 3,7,9 Dr Thomas Wild 10,11,12,13 1 School of Healthcare, Uiversity of Leeds, Leeds, UK 2 School of Nursig ad Midwifery, Natioal Uiversity of Irelad Galway, Galway, Irelad 3 Alliace for Research ad Iovatio i Wouds 4 Cliical Trials Research Uit, School of Medicie, Uiversity of Leeds, UK 5 Charite-Uiversitatsmedizi Berli, Berli, Germay 6 The Departmet of Nursig ad Midwifery, Uiversity of Limerick, Limerick, Irelad 7 Saolta Uiversity Health Care Group, Uiversity Hospital Galway, Galway, Irelad 8 Uiversity of Applied Scieces Wester Switzerlad, Geeva, Switzerlad 9 School of Medicie, Natioal Uiversity of Irelad Galway, Galway, Irelad 10 Uiversity Medical Ceter Hamburg- Eppedorf, Germay 11 Uiversity of Applied Sciece Ahalt, Istitute of Applied Biosciece ad Process Maagemet 12 Cliic of Plastic, Had ad Aesthetic Surgery, Medical Ceter Dessau, Academic Teachig Hospital of Mari Luther Uiversity of Halle- Witteburg, Germay 13 Cliic of Dermatology, Immuology ad Allergology, Medical Ceter Dessau, Academic Teachig Hospital of Mari Luther Uiversity of Halle-Witteburg, Germay REFERENCES 1. 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