D1.2 - Report on the initial Clinical Outcome Set

1 A new, in e disciplina y, mul i-s akeholde Eu opean ne wo k o imp o e heal hca e se ices, esea ch and ou comes o Adolescen s and Young Adul s wi h cance . STRONG-AYA – No. 101057482 – D1.2 Deli e able Repo WP1 – Repo on he ini ial Co e Ou come Se Deli e able 1.2 Repo on he ini ial Co e Ou come Se Due da e o deli e able: 30/09/2023 Ac ual submission da e: 28/03/2024 P ojec : STRONG-AYA Lead Con ibu o UOS- Ki s y Way, Anne-Sophie Da ling on, Nicole Collaço Email A.Da ling on@so on.ac.uk O he Con ibu o s NKI – Sil ie Janssen Emails [email p o ec ed]l Due da e 30 09 2023 Deli e y da e 28 03 2024 Deli e able ype R Dissemina ion le el PU Desc ip ion o Wo k Ve sion Da e V1.0 27/03/2024 STRONG-AYA – No. 101057482 – D1.2 Desc ip ion: This epo con ains he ini ial Co e Ou come Se , including he me hodology ha ook place o i s de elopmen . Resul s om he li e a u e e iew, quali a i e in e iews, Delphi su ey ounds as well as he consensus mee ing ha e been epo ed o show he p agma ic decision-making p ocesses behind he de elopmen o he Ini ial COS summa y (max ½ page) The aim o Wo k Package 1 (WP1) o STRONG AYA is o de elop a Co e Ou come Se (COS) o adolescen s and young adul s (AYAs) wi h cance . The e is speci ic scien i ic me hodology ha mus be ollowed o de elop a COS [1-4], as well as iden i y he measu emen s ins umen s o measu e he i ems in he COS [5]. The s ages o making decisions on he inal ou comes o be included in a COS a e h ee- old: (1) A e iew o he li e a u e o disco e which ou comes a e impo an o AYAs wi h cance , (2) quali a i e in e iews wi h s akeholde s (AYA pa ien s, hei ca egi e s, and heal hca e p o essionals) o hea hei pe cep ions o wha ou comes a e impo an o AYAs wi h cance , (3) consensus me hodology, known as a Delphi s udy. Following a e iew o he li e a u e and quali a i e in e iews, a o al o 129 ou comes we e accumula ed and conside ed impo an o AYAs wi h cance . These 129 ou comes we e hen ca ego ised in acco dance wi h Dodd’s 38-i em i em axonomy o ou comes in medical esea ch [6], which o med he skele on o he Delphi su ey. The Delphi su ey has a o al o h ee ounds, which aims o come o a consensus be ween s akeholde g oups on which ou comes a e he u mos impo an o measu e o AYAs wi h cance . Following he i s wo ounds o he Delphi su ey, a o al o 61 i ems me he inclusion c i e ia (ou comes ha ecei ed ≥70% esponden s a ing i as a 7-9 on he Like -scale) and we e aken o wa d o a consensus mee ing, which in ol ed 12 membe s o he STRONG AYA conso ium o ming an expe panel o make p agma ic decisions on he inal ou comes o be included in he Ini ial COS. The Ini ial COS consis s o 21 domains; he e a e 15 CORE domains, 3 ON TREATMENT domains and 3 OFF TREATMENT domains. The de elopmen o he Co e Measu emen Se o supplemen he ini ial COS is s ill being de eloped. Round 3 o he Delphi su ey is s ill ongoing; esul s om he hi d and inal Delphi ound will be used o in o m he Final COS. In he mean ime, he Ini ial COS will be implemen ed h oughou he heal hca e esea ch ecosys em in u u e wo k packages in he STRONG AYA p ojec STRONG-AYA – No. 101057482 – D1.2 1 Table o Con en s PUBLISHABLE SUMMARY (MAX ½ PAGE) .............................................................................................................. 3 1 TABLE OF CONTENTS ..................................................................................................................................... 4 2 DEFINITIONS ................................................................................................................................................. 5 3 ABBREVIATIONS............................................................................................................................................ 6 4 INTRODUCTION ............................................................................................................................................ 7 PROJECT BACKGROUND ...................................................................................................................................... 7 DELIVERABLE INTRODUCTION .............................................................................................................................. 9 5 DEVELOPING THE INITIAL CORE OUTCOME SET............................................................................................ 10 BACKGROUND ............................................................................................................................................................. 10 METHODS .................................................................................................................................................................. 10 Phase 1: Scope de ini ion .................................................................................................................................... 11 Phase 2: Es ablishing he need o a COS o AYAs ............................................................................................. 11 Phase 3: Composi ion o AYA Wo king G oup .................................................................................................... 11 Phase 4: S udy p o ocol de elopmen ................................................................................................................ 12 Phase 5: De e mine “wha ” o measu e – he ou comes in he COS .................................................................. 12 Phase 6: De e mine “how” o measu e he COS ................................................................................................. 21 De e mine “case-mix a iables” ......................................................................................................................... 23 RESULTS .................................................................................................................................................................... 23 The Li e a u e Re iew ......................................................................................................................................... 23 Quali a i e In e iews ........................................................................................................................................ 24 The Delphi su ey ............................................................................................................................................... 25 FUTURE WORK ............................................................................................................................................................ 30 6 CONCLUSION ............................................................................................................................................... 31 7 REPOSITORY FOR PRIMARY DATA (ANNEX) ................................................................................................. 31 STRONG-AYA – No. 101057482 – D1.2 2 De ini ions STRONG AYA conso ium membe s a e e e ed o as ollowing wi hin his ex : 1. NKI-AVL – S ich ing he Nede lands Kanke Ins i uu – An oni an Leeuwenhoek Ziekenhuis (NL) 2. YCE – You h Cance Eu ope (RO) 3. INT – Fondazione IRCCS Ins i u o Nazionale dei Tumo i (IT) 4. FFUND – FFUND BV (NL) 5. CLB – Cen e de Lu e Con e le Cance Leon Be a d (FR) 6. ECO – Eu opean Cance O ganisa ion (BE) 7. UNIMAAS – Uni e si ei Maas ich (NL) 8. IKNL – S ich ing In eg aal Kanke cen um Nede land (NL) 9. EORTC – Eu opean O ganisa ion o Resea ch and T ea men o Cance AISBL (BE) 10. IGR – Ins i u Gus a e Roussy (FR) 11. MSCNRIO – Na odowy Ins y u Onkologii im. Ma ii Sklodowskiej-Cu ie – Pans wowy Ins y u Badawczy (Ma ie Sklodowska-Cu ie Na ional Resea ch Ins i u e o Oncology) (PL) 12. UOM – Uni e si y o Manches e (UK) 13. UOL – Uni e si y o Leeds (UK) 14. LTHT – Leeds Teaching Hospi als Na ional Heal h Se ice T us (UL) 15. SOUTHAMPTON – Uni e si y o Sou hamp on (UK)  G an Ag eemen (including i s annexes and amendmen s): he ag eemen signed be ween he bene icia ies o he HORIZON Resea ch and Inno a ions Ac ions (he ea e e e ed o as Ho izon) and he Eu opean Heal h and Digi al Execu i e Agency (he ea e e e ed o as HADEA) o he unde aking o he STRONG AYA p ojec (G an Ag eemen no. 101057482).  Bene icia y: Signa o ies o he G an Ag eemen  Associa ed Pa ne : En i ies which pa icipa e in he ac ion bu wi hou he igh o cha ge cos s o claim con ibu ions.  P ojec : he sum o all ac i i ies ca ied ou in he amewo k o he G an Ag eemen .  Conso ium: he STRONG AYA conso ium, including all he a o emen ioned pa ne s.  Conso ium Ag eemen : The ag eemen made be ween STRONG AYA membe s o he implemen a ion and execu ion o he ac ion ou lined in he G an Ag eemen . The ag eemen shall no a ec he pa ies’ obliga ions o HADEA on behal o he Eu opean Union, and/o o one ano he a ising om he G an Ag eemen . STRONG-AYA – No. 101057482 – D1.2 3 Abb e ia ions Ac onym/Abb e ia ion Meaning HCP Heal h Ca e P o ide PRO Pa ien Repo ed Ou come PROM Pa ien Repo ed Ou come Measu e COS Co e Ou come Se WP Wo k Package WPL Wo k Package Lead(s) WP1 Wo k Package 1 (De elopmen Co e Ou come Se AYA wi h cance & da a collec ion) WP2 Wo k Package 2 (Go e nance, Da a Secu i y and E hics) WP3 Wo k Package 3 (In as uc u e and In e ope abili y) WP4 Wo k Package 4 (Ope a ion o STRONG AYA ecosys ems, s akeholde and pa ien in ol emen , dissemina ion, exploi a ion, communica ion) WP5 Wo k Package 5 (Scien i ic coo dina ion and p ojec managemen ) KPI Key Pe o mance Indica o OA Open Access PAB Pa ien Ad iso y Boa d EC Eu opean Commission HADEA Eu opean Heal h and Digi al Execu i e Agency SC S ee ing Commi ee MT Managemen Team STRONG-AYA – No. 101057482 – D1.2 4 In oduc ion P ojec backg ound Cance a adolescen and young adul (AYA) age is a e, al hough 4-6 imes mo e equen han paedia ic cance (i.e. p epubescen pe iod). Howe e , his a i y does no e lec he signi ican pe sonal and socie al cos s o cance in his popula ion, as e lec ed in he po en ial yea s o li e los o sa ed, he dec eased p oduc i i y and quali y-o -li e due o he impac o he disease du ing o ma i e yea s, and he long- e m complica ions o disabili ies1. AYAs wi h cance o m a unique g oup; hey ace age-speci ic issues (e.g. In e ili y, unemploymen , inancial p oblems) and dec eased quali y o li e due o cance and i s ea men . Unlike dedica ed heal hca e and ials o paedia ic cance pa ien s, AYA-speci ic heal hca e se ices a e sca ce and a y ac oss Eu ope. AYAs who a e a he co e o socie y and economy need access o age-app op ia e and high-quali y heal hca e. De ining AYAs wi h cance as 15 o 39 yea s a ini ial cance diagnosis2, hei annual cance incidence is 42.2/100.000, wi h 156.431 cases in Eu ope and 1.231.007 cases wo ldwide epo ed in 2018 ( oge he 6.8% o all cance s)3. Popula ion-based da a om 27 Eu opean coun ies suppo s ha AYAs ha e lowe su i al han child en bu highe han adul s a ec ed by cance . Ad ances in cance ea men ha e led o inc eased su i al a es o AYAs wi h cance , imp o ing by 82% o all cance s be ween 1990 and 20074. Howe e , su i al imp o emen in AYA is mo e challenging han o child en and olde cance su i o s, which migh be due o he ac ha AYA ha e he highes absolu e excess isk o second p ima y malignan neoplasms5. AYA ace some dis inc challenges gi en ha hey do no belong o nei he paedia ic no adul oncology g oups. Cha ac e is ic ea u es o his popula ion g oup include unique spec um o cance ypes, di e en umou biology, unique complex psychological needs, dis inc la e sequelae, including impai ed e ili y, and pallia i e ca e. These ai s imply ha clinical managemen , ea men , diagnosis, psychological suppo will need o be designed and de eloped o AYA’s speci ic needs. Fo example, AYAs diagnosed wi h b eas and p os a e ca cinomas ha e wo se su i al han olde pa ien s because o he biological di e ences be ween hem, highligh ing he need o a ge sc eening me hodologies, ea men and policies o hei needs6. AYAs wi h cance also ace signi ican psychological challenges, including subs ance abuse, men al heal h issues, suicidal idea ions and inc eased emo ional bu den om cance and cance - ela ed mo bidi y. Finally, ailo ing cance ca e o AYA’s needs is di icul and due o many di e en complex ac o s including he low a e o pa icipa ion by AYAs in clinical ials and cance esea ch7. 1 S oneham SJ. AYA su i o ship: The nex challenge. Cance 2020; 126: 2116-2119. 2 Adolescen and Young Adul Oncology Re iew G oup. Closing he gap: Resea ch and Ca e Impe a i es o Adolescen s and Young Adul s wi h Cance . Na ional Ins i u e o Heal h, Na ional Cance Ins i u e, and Li es ong Young Aul Alliance: Be hesda, MD, USA, 2006. 3 T ama A, Bo a L, S elia o a-Fouche E. Cance Bu den in Adolescen s and Young Adul s: A Re iew o Epidemiological E idence. Cance J 2018; 24: 256- 266 4 T ama A, Bo a L, Foschi R e al. Su i al o Eu opean adolescen s and young adul s diagnosed wi h cance in 2000-07: popula ion-based da a om EUROCARE-5. Lance Oncol 2016; 17: 896-906. 5 Keegan THM, Bleye A, Rosenbe g AS e al. Second P ima y Malignan Neoplasms and Su i al in Adolescen and Young Adul Cance Su i o s. JAMA Oncol 2017; 3: 1554-1557. 6 S a k D, Bielack S, B ugie es L e al. Teenage s and young adul s wi h cance in Eu ope: om na ional p og ammes o a Eu opean in eg a ed coo dina ed p ojec . Eu opean Jou nal o Cance Ca e, 25(3), 419–427. 7 Hayashi RJ. Adolescen and young adul cance su i o ship: The new on ie o in es iga ion. Cance 2019; 125: 1976-1978. STRONG-AYA – No. 101057482 – D1.2 Despi e he inc easing awa eness and a g owing body o he scien i ic li e a u e, hese unique issues emain o be ully ecognised and add essed by he Eu opean heal h sys ems and AYAs wi h cance a e equen ly unde se ed. In pa , his may ha e esul ed om he adi ional dicho omy be ween he in eg a ed paedia ic (“pa ien / amily-cen ed”) ca e se ices e sus dispe sed (“disease- cen e ed”) adul oncology se ices8,9,10. Up o hal o AYAs wi h cance epo unme in o ma ional and se ice needs, impac ing hei di ec (su i al a es) and indi ec (long e m e ec s and men al heal h) eco e y o pa icipa e in socie y11. Fu he mo e, aligned wi h his ba ie is he low a e o heal h ca e u ilisa ion by AYAs, especially p ima y ca e, gi en hei challenges o sus ain heal h insu ance co e age12. Acco ding o a su ey conduc ed h ough he ne wo ks o he AYA Wo king G oup o he Eu opean Socie y o Medical Oncology (ESMO) and he Eu opean Socie y o Paedia ic Oncology (SIOP Eu ope), 67% o p ac i ione s do no ha e access o specialised cen es o AYA wi h cance , 67% had no access o a specialis cance se ice o la e e ec s managemen and 38% had no access o e ili y specialis s. Unde -p o ision and inequali y o AYA cance ca e is common ac oss Eu ope and especially in he Eas e n and Sou he n-Eas . Fu he mo e, he Wo king G oup also epo ed an absence o ou come measu es o moni o ing and e alua ing AYA cance ca e p og ams and con ol13. Among he ecommended u u e s eps, i has been iden i ied ha one o he mos impo an con ibu ions o AYA esea ch would be o pool da a (e.g. pa ien - epo ed ou comes, clinical and ea men da a) ac oss ins i u ions and coun ies and c ea e la ge coho s o esea che s o Add ess he bu den o cance in AYA14. The e is a lack o da a s anda diza ion, da a in e ope abili y and (p ospec i e) collec ion o ou comes o ele ance o AYAs wi h cance . The STRONG-AYA p ojec aims o ackle he unde ep esen a ion o AYA’s expe iences and ou comes when na iga ing he heal hca e sys em and in clinical ca e by de eloping na ional in as uc u es o ou come da a managemen and clinical decision-making wi hin a pan-Eu opean ecosys em and es ablishing communica ion eedback o AYAs wi h cance and he heal hca e sys ems. This will be key o imp o ing heal hca e se ices, esea ch, ou comes and policies o AYAs and o ul ima ely be e cance ca e o his pa ien g oup. To his aim, STRONG-AYA b ings oge he an in e na ional mul i-disciplina y conso ium ac oss se en Eu opean coun ies, led by he Ne he lands Cance Ins i u e (NKI) and composed o academic esea ch o ganisa ions (Eu opean O ganisa ion o Resea ch and T ea men o Cance (EORTC), Uni e si y o Sou hamp on, Uni e si y o Leeds, Uni e si y o Manches e , Maas ich Uni e si y, Ne he lands Comp ehensi e Cance O ganisa ion (IKNL)), clinical pa ne s (I alian Na ional Tumou Ins i u e, Léon Bé a d Cen e, Gus a e Roussy Ins i u e, Ma ia Sklodowska-Cu ie Na ional Resea ch Ins i u e o Oncology, he Leeds Teaching Hospi als Na ional Heal h Se ice T us ), s akeholde and pa ien o ganisa ions (You h Cance Eu ope, Eu opean Cance O ganisa ion) and a consul ing company (FFUND). 8 Fe a i A, S a k D, Pecca o i FA e al. Adolescen s and young adul s (AYA) wi h cance : a posi ion pape om he AYA Wo king G oup o he Eu opean Socie y o Medical Oncology (ESMO) and he Eu opean Socie y o Paedia ic Oncology (SIOPE). ESMO Open 2021; 6: 100096. 9 Osbo n M, Johnson R, Thompson K e al. Models o ca e o adolescen and young adul cance p og ams. Pedia Blood Cance 2019; 66: e27991. 10 Fa dell JE, Pa e son P, Wake ield CE e al. A Na a i e Re iew o Models o Ca e o Adolescen s and Young Adul s wi h Cance : Ba ie s and Recommenda ions. J Adolesc Young Adul Oncol 2018; 7: 148-152. 11 Keegan TH, Lich ensz ajn DY, Ka o I e al. Unme adolescen and young adul cance su i o s in o ma ion and se ice needs: a popula ion-based cance egis y s udy. J Cance Su i 2012; 6: 239-250. 12 Hayashi RJ. Adolescen and young adul cance su i o ship: The new on ie o in es iga ion. Cance 2019; 125: 1976-1978. 13 Salous os E, S a k D, Michailidou K e al. Repo on ESMO/SIOPE Eu opean Landscape p ojec key esul s: Mapping he s a us and needs in AYA cance ca e. La e-b eaking and de e ed publica ion abs ac s public heal h 2017; 28, 5: V643. 14 Smi h AW, Seibel NL, Lewis DR e al. Nex s eps o adolescen and young adul oncology wo kshop: An upda e on p og ess and ecommenda ions o he u u e. Cance 2016; 122: 988-999. STRONG-AYA – No. 101057482 – D1.2 Building on p e ious ini ia i es, a STRONG-AYA da a ecosys em will be se up o alue-based ca e, esea ch and policy o AYA wi h cance by: 1. De eloping a Co e Ou come Se (COS) speci ically o AYAs wi h cance , ia a pa icipa i e consensus p ocess de ining mos impo an aspec s o hose di ec ly a ec ed by AYA cance , including pa ien s and heal hca e p o essionals. 2. Implemen ing he COS ac oss se e al na ional Eu opean heal hca e sys ems. Da a will be collec ed a local le el and will hen be included in a da a in eg a ion pla o m. An o e all ecosys em amewo k o da a analy ics and ou pu will be c ea ed suppo ing ede a ed analyses and he c ea ion o epo s ac oss clinical and pa ien - epo ed da a and making na ional eposi o ies o (pa ien - epo ed) heal h da a, a ailable o indi idual pa ien s, pa ien o ganisa ions, egula o y au ho i ies, as well as he pa ien s’ heal h ca e p o ide s o in o m clinical decision-making. The i e esul ing na ional ecosys ems will be connec ed o each o he in o he pan-Eu opean ecosys em using a ede a ed app oach also u ilizing he o e all ecosys em amewo k. 3. Dissemina ing he COS o a wide ange o local as well as pan-Eu opean s akeholde s, in pa icula by de eloping analy ical ools o p ocess and p esen pa ien ou come da a and es ablish eedback loops ha in o m pa ien s and clinicians. Implemen ing hese p ojec objec i es a e i e wo k packages wi hin he STRONG-AYA p ojec :  WP1: De elopmen Co e Ou come Se AYA wi h cance and Da a Collec ion (Lead: SOUTHAMPTON)  WP2: Go e nance, Da a Secu i y and E hics (Lead: EORTC)  WP3: In as uc u e and In e ope abili y (Lead: UNIMAAS)  WP4: Ope a ion o STRONG-AYA ecosys ems, S akeholde and Pa ien in ol emen , Dissemina ion, Exploi a ion, Communica ion (Lead: E.C.O.)  WP5: Scien i ic Coo dina ion and P ojec Managemen (Lead: NKI) STRONG-AYA will enable AYA ca e and esea ch o bene i om collec ion and pooling o pa ien -cen e ed da a and collabo a ion among all s akeholde s: pa ien s, heal hca e p o essionals, scien is s, and policymake s. Mo e widely, he p ojec will le e age he ne wo k o in e es ed o ganisa ions and ne wo ks es ablished unde STRONG-AYA o long- e m s eng hened p omo ion o he necessa y implemen a ion o specialis AYA cance se ices ac oss Eu ope. This will ul ima ely b ing no el insigh s in o AYA cance ca e, esea ch and policy, con ibu ing o he long- e m imp o emen o ou comes o people wi h AYA cance . Deli e able in oduc ion WP1 (de eloping a Co e Ou come Se ): The o e all aim o WP1 is o de elop a Co e Ou come Se (COS) o AYAs wi h cance . We aim o assess which ou comes, including pa ien - epo ed ou comes, clinical, and ea men ela ed ou comes, a e mos impo an o measu e o AYAs wi h cance , om he poin o iew o AYAs wi h cance , hei ca egi e s, heal hca e p o essionals, esea che s and policymake s. The p ocess o de eloping a COS is ou lined in se e al guidance documen s, and ollows a clea p ocess [1-4]. This includes adhe ing o he 11 minimum s anda ds o Co e Ou come Se -STAnda ds o De elopmen (COS-STAD) [2] and he 13 i ems conside ed essen ial documen a ion as desc ibed in he Co e Ou come Se -STAnda dised P o ocol I ems (COS-STAP) [3]. STRONG-AYA – No. 101057482 – D1.2 in which ou comes we e ex ac ed and ca ego ized in o ele an domains. Ou comes we e coun ed o iden i y weigh o domains. The Delphi p ocess The Delphi echnique is a mul is age p ocess, designed o ans o m opinion in o consensus by i e a i e ounds o ques ionnai es, in e spe sed wi h con olled eedback [14]. Anonymi y o indi idual panel membe s wi hin speci ic s akeholde g oups emo es inhe en bias, such as g oup con o mi y, as pa icipan s do no in e ac di ec ly wi h each o he , so si ua ions whe e he g oup is domina ed by he iews o ce ain indi iduals can be a oided [15]. Delphi s udies a e ypically 2-3 ounds, al hough aspec s o i s me hodology can be in e p e ed in a a ie y o ways. Delphi su ey de elopmen The ou comes iden i ied as ele an o AYAs wi h cance ia he e iew o he li e a u e (s ep 1) and he quali a i e in e iews (s ep 2) o med an ini ial lis , which would be aken o wa d o he i s ound o he Delphi su ey. The ini ial lis o ou comes we e ca ego ized using Dodd’s 38-i em axonomy o ou comes in medical esea ch [6], and o med he skele on o he Delphi su ey (Table 3). The axonomy was adap ed, in e ms o o de o ou comes and speci ic wo ding, o adjus o he lay audience o his Delphi su ey. The o de ing o domains in he axonomy was also adjus ed o imp o e he cohe ence o he su ey, o he pu poses o he Delphi. Table 3: The skele on o he Delphi su ey, using an adap ed e sion o Dodd’s 38-i em axonomy o ou comes in medical esea ch [6] Dodd’s 38-i em axonomy o ou comes in medical esea ch Ou comes o disease Mo ali y/su i al Physiological/clinical Ou comes ela ing o neoplasms Ca diac ou comes Ci cula ion (blood, ascula and lympha ic sys em) ou comes Respi a o y sys em (ches and lungs) ou comes S omach (gas oin es inal) and diges ion ou comes Ne ous sys em ou comes Kidney and u ina y sys em ou comes Li e and panc eas (hepa obilia y) ou comes Immune sys em ou comes In ec ion ou comes Ea , hea ing, and balance ou comes Eyes and ision ou comes Skin and subcu aneous issue ou comes Musculoskele al and connec i e issue ou comes Nu i ion and me abolism ou comes Inju y and poisoning ou comes STRONG-AYA – No. 101057482 – D1.2 Musculoskele al and connec i e issue ou comes Ho mones (endoc ine sys em) ou comes Rep oduc i e sys em ou comes P egnancy and childbi h (be o e, du ing and a e childbi h) ou comes Gene ic ou comes Psychia ic ou comes Gene al ou comes Func ioning Physical unc ioning Social unc ioning Role Func ioning Emo ional and Psychological Func ioning / Wellbeing Cogni i e Func ioning Global Quali y o Li e Pe cei ed Heal h S a us Deli e y o Ca e Pe sonal Ci cums ances Resou ce Use Economic Hospi al Need o u he in e en ion Socie al and ca e bu den Ad e se e en s / e ec s D a e sions o he su ey i ems we e e alua ed by 8 membe s o he STRONG AYA conso ium, including wo k package leads (n = 2), esea che s (n=2) and HCPs (n = 4). This was o ensu e all ou comes we e: (1) ph ased in layman’s e ms o ensu e pa icipan s could accu a ely in e p e hem, and (2) ca ego ized co ec ly acco ding o he axonomy. The leng h o he su ey was highligh ed as an o e a ching conce n; he e o e, e o s we e made o elimina e any po en ial epe i i eness in ou come i ems and hus educe he o e all numbe o i ems o be included. The inal lis o ou comes, as well as he su ey ins uc ions, we e pilo es ed by h ee esea che s wi hin he STRONG AYA conso ium, and eedback was p o ided. This was o es he usabili y o he su ey pla o m, as well as he in e p e a ions o each ou come. Rec ui men o he Delphi su ey The Delphi p ocess was comp ised o h ee expe s akeholde panels: (4) AYAs (aged 15-39 a diagnosis) and ca egi e s (including pa en s / gua dians, amily membe s, pa ne s and ca egi e s). (5) Heal hca e p o essionals who p o ide ca e o AYAs wi h cance . (6) Resea che s and policymake s who a e ac i e in he ield o AYAs wi h cance . STRONG-AYA – No. 101057482 – D1.2 The ec ui men a ge o he Delphi su ey was 100 pa icipan s pe s akeholde g oup (300 in o al). This would allow o d op-ou a es mo ing in o subsequen Delphi ounds. Rec ui men ma e ials we e de eloped, including a 1-Page ec ui men le e ou lining he s udy, email empla es, and social media ad e s. Pa icipan s o each s akeholde g oup we e ec ui ed in he ollowing ways: Table 4: Desc ip ion o he ec ui men s a egies o each s akeholde g oup in he Delphi su eys (1) AYAs and Ca egi e s (2) Heal hca e p o essionals (3) Resea che s and policymake s AYAs and ca egi e s ha ook pa in he quali a i e in e iews we e asked i hey would also like o ake pa in he Delphi su ey. Heal hca e p o essionals ha ook pa in he quali a i e in e iews we e asked i hey would also like o ake pa in he Delphi su ey. Resea che s we e con ac ed ia hei email add esses which we e ound in ecen publica ions in AYA jou nals (e.g. Jou nal o Adolescen and Young Adul Oncology). You h Cance Eu ope a e a cha i y made up o you h cance o ganisa ions ac oss Eu ope. A con ac a he cha i y con ac ed po en ial pa icipan s o in i e hem o ake pa in he Delphi su ey. They also ad e ised h ough social media channels (LinkedIn, Facebook). The Eu opean Socie y o Paedia ic Oncology (SIOPE) is a pan-Eu opean o ganisa ion ep esen ing all p o essionals wo king in he ield o childhood and AYA cance s. They sha ed he ec ui men le e wi h all membe s o he Eu opean Ne wo k o Teenage s and Young Adul s wi h Cance (ENTYAC). Resea che s p o ided con ac de ails o o he esea che s who may wish o ake pa . The You h and Cance Founda ion (S ich ing Jonge en en Kanke ) is a pa ien o ganisa ion o AYAs wi h cance . They sha ed he social media ad e s ia hei Ins ag am and Facebook s o ies. The Eu opean Cance O ganisa ion (ECO) a e ne wo k o oncology p o essionals and cance pa ien s. They ad e ised he Delphi su ey in hei mon hly newsle e . The Eu opean Cance O ganisa ion (ECO) a e ne wo k o oncology p o essionals and cance pa ien s. They ad e ised he Delphi su ey in hei mon hly newsle e . The Eu opean Cance O ganisa ion (ECO) a e ne wo k o oncology p o essionals and cance pa ien s. They ad e ised he Delphi su ey in hei mon hly newsle e . Pa icipan s sha ed wi h hei ne wo ks o HCPs a local hospi als. Pa icipan s di ec ed o he AYAs and ca egi e s o ake pa , h ough wo d o mou h HCPs ale ed hei AYA pa ien communi y, ia communi y pa ien g oups and local cha i ies. STRONG-AYA – No. 101057482 – D1.2 o ad e isemen s in hei local cance communi ies. Su ey da a collec ion p ocedu e The online su ey pla o m used o collec esponses was Qual ics (h ps://www.qual ics.com/uk/). The pa icipan in o ma ion shee was p o ided a he s a o he su ey, as well as a checkbox o pa icipan s o p o ide hei consen o aking pa . Pa icipan s we e eminded o hei igh o wi hd aw om he s udy a any ime, p i acy and accessibili y in o ma ion, and how hei da a will be used. Ini ial, gene ic demog aphic ques ions ( ele an o all s akeholde g oups) we e included a he s a o he su ey o collec in o ma ion, such as: age, gende , e hnici y, coun y o esidence, educa ion, and socioeconomic s a us. Speci ic demog aphic ques ions ele an o sepa a e s akeholde g oups we e hen asked. Fo example, AYAs we e asked abou hei diagnosis ype, age a diagnosis, ea men s a us, and clinic- ype. Ca egi e s we e asked he same ques ions, in ela ion o he AYAs hey ca e o . HCPs, esea che s and policymake s we e asked ques ions ela ing o hei p o ession, yea s’ expe ience, and hei expe ise wi hin hei p o ession. Ou Delphi p ocess included h ee su ey ounds: (1) Ini ial i em a ing, wi h all 129-ou comes (2) I em e- a ing, wi h eedback om p e ious su ey ound (3) I em anking, choosing a op 15 ou comes o on and o ea men * * Round 3 o he Delphi su ey is cu en ly unde way a he ime o his epo Round 1 o he Delphi Su ey Following demog aphic ques ions, he su ey asked pa icipan s o a e he impo ance all 129 ou comes on a 9-poin Like Scale, as pe ecommenda ions ou lined by he GRADE wo king g oup [16]. A a ing scale o “no impo an ” ( a ing o 1–3), “impo an , bu no c i ical” ( a ing o 4–6), o “ex emely impo an / c i ical” ( a ing 7–9) was p o ided. An op ion o “unable o answe ” was also p o ided. I was explained o pa icipan s ha hey should no a e oo many ou comes as “ex emely impo an ”, as he end-goal was o ha e only app oxima ely 10-15 ou comes ha a e kep o inclusion in he inal COS. Pa icipan s we e eminded on each page o he su ey ha hey should a e he ou comes wi h emphasis on he AYA (aged 15-39) demog aphic, o a oid esul ing in a COS ha is no speci ic o he AYA age-g oup. Pa icipan s we e equi ed o p o ide a a ing o e e y i em in he su ey. A he end o he su ey was an open- ex box o pa icipan s o p o ide any ou comes hey hough we e missing in he su ey, ha we e impo an o measu e o AYAs wi h cance . T ansla ions o he su ey we e p o ided o he ollowing languages: Du ch, F ench, I alian, Ge man, Spanish and Polish. This was o inc ease he each and cul u al di e si y o he Delphi su ey. Round 2 o he Delphi Su ey STRONG-AYA – No. 101057482 – D1.2 The second su ey ound included he same ini ial demog aphic ques ions as ound 1. Pa icipan s we e p o ided wi h a pe sonalised URL, he e o e hei esponses o he demog aphic ques ions we e sa ed and ca ied o wa d om ound 1 and hey we e able o make changes (i necessa y). The concep o a second Delphi su ey ound is o p o ide eedback o pa icipan s o he esul s om ound 1, and allow hem o po en ially change hei a ing on he 9-poin Like scale, o begin a con e gence o opinion (consensus) and come o an ag eemen on he mos impo an ou comes o measu e o AYAs wi h cance . Feedback om ound 1 was p o ided as a pe cen age abo e each numbe on he Like scale (i.e. a pe cen age o how many o he pa icipan s in hei s akeholde g oup a ed he ou come as X le el o impo ance). Pa icipan s we e also p o ided wi h hei o iginal a ing om ound 1 as a p e- illed do on he Like scale. See Figu e 3. All i ems lis ed in ound 1 o he Delphi su ey we e ca ied o wa d o ound 2. Pa icipan s we e also asked o a e six addi ional ou comes ha pa icipan s had lis ed as impo an ye missing om ound 1 (using he open ex box). Figu e 3: A snapsho o ound 2 o he Delphi su ey, e idencing he use o eedback (%) and p e iewing pa icipan ’s ound 1 esponses. Consensus mee ing In o de o an Ini ial COS o be de eloped in ime o begin implemen a ion o da a collec ion h oughou he heal hca e esea ch ecosys em o he STRONG AYA p ojec , a consensus mee ing was scheduled p io o conduc ing Round 3 o he Delphi su ey. This was o allow decisions o be made ega ding he ou comes o be included in he ini ial COS. This mee ing ook place on 18/01/2024 and a endees included 12 pa icipan s om he STRONG AYA conso ium, who o med an expe panel. All ou comes ha ecei ed ≥70% esponden s a ing i as a 7-9 on he Like -scale, ac oss all s akeholde g oups, we e p esen ed o he expe panel. Based on discussions ega ding he di icul y o dis inguishing STRONG-AYA – No. 101057482 – D1.2 he mos impo an ou comes o AYAs wi h cance , i was decided ha he ini ial COS would iden i y ou comes o bo h ON and OFF ea men phases. The de ini ions o ON and OFF ea men we e as ollows: On ea men = a cance pa ien ecei ing cu a i e ea men , including main enance ea men , who is no belie ed o be disease- ee. O ea men = a cance pa ien ea ed wi h cu a i e in en , who is disease- ee, o ecei ing li e- ex ending o pallia i e ea men / ca e An online poll ook place (using a polling pla o m, Ve ox) whe eby pa icipan s we e asked o selec he mos impo an 15 ou comes o measu e o AYAs wi h cance o bo h ON and OFF ea men . The numbe “15” was decided ollowing explo a ion o he li e a u e and a e aging he numbe o COS i ems o cance COS published since 2020. Resul s om his mee ing we e used o in o m he i s d a o he Ini ial COS. This d a o he Ini ial COS was ci cula ed o he STRONG AYA conso ium, plus membe s o he public ad iso y boa d o eedback. Feedback was p o ided om 7 esea che s and HCPs in he STRONG AYA conso ium and 4 pa ien ad iso y boa d membe s. Round 3 o he Delphi Su ey Round 3 aims o pa icipan s o be mo e succinc wi h hei decision making. Any ou come ha ecei ed ≥70% esponden s a ing i as a 7-9 on he Like -scale was ca ied o wa d o ound 3 o he Delphi p ocess, pe s akeholde g oup. Fo example., he AYA and pa en /ca egi e s akeholde panel we e only p esen ed wi h he lis o ou comes ha ecei ed ≥70% esponden s a ing i as a 7-9 on he Like -scale by hei s akeholde g oup (see Table 6) . Simila o he consensus mee ing, pa icipan s we e asked o iden i y he op 15 ou comes o AYAs wi h cance , whils bo h ON and OFF ea men . Addi ionally, hey we e asked o hen ank he op 15 ha hey chose, in o de o “mos impo an ” and “leas impo an ”, o bo h ON and OFF ea men . I is hoped ha his me hodology will elici g ea e consensus om s akeholde g oups, hus esul ing in he Final COS. Round 3 is cu en ly ongoing a he ime o his epo , and is due o close wi hin he upcoming weeks. Resul s om his su ey ound will hen in o m he Final COS. Phase 6: De e mine “how” o measu e he COS A join ini ia i e be ween he COnsensus-based S anda ds o he selec ion o heal h Measu emen INs umen s (COSMIN) ini ia i e [5] and he COMET ini ia i e [1] ha e de eloped a guideline on how o selec measu emen ins umen s o ou comes included in a COS (Figu e 4). STRONG-AYA – No. 101057482 – D1.2 Figu e 4: Flowcha o he selec ion o ou come measu emen ins umen s o COS [17] S ep 4: Selec one ins umen o each ou come in he COS Use a consensus p ocedu e o ag ee on he ins umen s o each ou come included in he COS E alua e he me hodological quali y o he s udies on measu emen p ope ies E alua e he quali y o he me hodological measu emen p ope ies Combine he e idence on he me hodological quali y o he s udies wi h he quali y o he measu emen p ope ies E alua e he easibili y o he ins umen s Pe o m a new li e a u e sea ch Upda e he li e a u e sea ch S ep 3: E alua e he quali y o he ins umen s No, no up- o-da e No, o poo quali y No, quali y assessmen no pe o med S ep 1: Concep ual conside a ions De ine cons uc o be measu ed De ine a ge popula ion S ep 2: Find all exis ing ins umen s Is a good quali y, up- o-da e sys ema ic e iew o ou come measu emen s a ailable? STRONG-AYA – No. 101057482 – D1.2 To de elop he Co e Measu emen Se o he Ini ial COS, he guidelines p oposed in Figu e 4 we e ollowed, wi h he excep ion o upda ing / pe o ming a li e a u e sea ch in he absence o a good quali y, up- o-da e e iew. The consensus p ocess (s ep 4) will be in he o m o a mee ing due o ake place on 26 h Ma ch 2024, whe eby membe s o he STRONG AYA conso ium om he Uni e si y o Sou hamp on and NKI will mee o make p agma ic decisions on which a e he mos sui able measu emen ools, in e ms o hei psychome ic p ope ies, accessibili y, ansla ion a ailabili y, and numbe o i ems/subscales. Once he Final COS has been de eloped, he scien i ic p ocess o measu emen ins umen selec ion de ailed in Figu e 4 will be ollowed ex ensi ely. De e mine “case-mix a iables” As pa o he da a ex ac ion p ocess o he li e a u e e iew (see sec ion 5.5.1), case mix a iables published in he li e a u e we e collec ed. These will hen be pooled and analysed, eady o implemen a ion alongside he Ini ial COS in u u e wo k packages in he STRONG AYA p ojec . This p ocess is ongoing a he ime o his epo . Resul s The Li e a u e Re iew A o al o 14 e iewe s om he STRONG AYA conso ium conduc ed i le and abs ac sc eening, and ull ex sc eening. 15 e iewe s conduc ed da a ex ac ion. The ini ial sea ch iden i ied 37127 eco ds h ough he i e da abases (Figu e 5). A e duplica es we e emo ed, he sea ch e u ned 19826 eco ds. Following sc eening 17301 eco ds on i le and abs ac s, 11727 eco ds we e excluded. This esul ed in 5574 eco ded being assessed o eligibili y, om which 2980 we e excluded. In o al, 2594 s udied we e included in he e iews; ou comes om hese eco ds we e colla ed and in o med he de elopmen o he Delphi su ey. Impo an ly, e inemen o he li e a u e sea ch is s ill ongoing a he ime o his epo . The numbe o a icles epo ed din Figu e 5 we e accu a e o de eloping an ini ial lis o ou comes o he Delphi su ey, howe e mo e a icles ha e been excluded since his poin , and mo ing o wa ds o he w i e up o he Li e a u e Re iew. STRONG-AYA – No. 101057482 – D1.2 Figu e 5: Flow cha o s udy sc eening and inclusion p ocess, acco ding o he PRISMA F amewo k. Quali a i e In e iews A o al o 56 in e iews we e conduc ed be ween Ap il 2023-June 2023; 27 AYAs, 4 pa en s / ca egi e s, and 25 HCPs. Demog aphic in o ma ion and esul s ela ing o he p oduc ion i a digi al ool o he STRONG AYA p ojec a e ou lined in Deli e able 1.11. A hema ic con en analysis esul ed in 22 ou come domains ha we e pe cei ed as impo an o AYAs wi h cance . Table 5 summa ises he domains iden i ied in he in e iews, including which s akeholde g oup iden i ied wha as impo an . These 22 domains, plus he indi idual ou comes wi hin each domain, we e hen o in o m he p oduc ion i he Delphi su ey. Iden i ica ion o s udies ia da abases and egis e s Reco ds iden i ied h ough da abase sea ching (n = 37127): Medline ALL (n = 13088) Embase (n = 12039) Web o Science Co e Collec ion (n = 11146) Coch ane Cen al Regis e o Con olled T ials (n = 654) Google Schola (n = 200) Duplica e eco ds emo ed be o e sc eening (n = 19826): Medline ALL (n = 119) Embase (n = 10089) Web o Science Co e Collec ion (n = 9021) Coch ane Cen al Regis e o Con olled T ials (n = 420) Google Schola (n = 177) Reco ds sc eened on i le and abs ac (n = 17301) Reco ds Excluded (n = 11727) Full ex eco ds assessed o eligibili y (n = 5574) Reco ds excluded (n = 2980): S udies included in e iew (n = 2594): Iden i ica ion Sc eening Inclusion STRONG-AYA – No. 101057482 – D1.2 Table 5: Domain esul s om he hema ic con en analysis o he quali a i e in e iews, pe s akeholde g oup Domain AYAs HCPs Pa en s / ca egi e s Fe ili y X X X Rela ionships/sexual in imacy X X X Changes o amily dynamics/ oles X X X Men al heal h/psychological X X X Iden i y X X Social unc ioning (excl. oman ic ela ionships) X X X Connec ing o o he pee s wi h cance o he same li e s age X Educa ion X X X Wo k (posi i e) X X Wo k (nega i e) X X Financial implica ions X X X Body image (sel -es eem) X X Su i al/mo ali y X X X Loss o con ol X Loss o independence X X X Long e m e ec s o cance and ea men /a ec s pos ea men X X Li ing wi h and beyond cance X X X Managing impac s on daily ou ines/li es X Beha iou X X Heal hca e X X X Physical X X Cogni i e X The Delphi su ey Gene a ing he ini ial lis o ou comes