Preference-based measures of healthrelated quality of life in congenital mobility impairment: A systematic review of validity and responsiveness

B ay, Na han; Spence , Llinos Ha ; Edwa ds, Rhiannon Edwa ds A icle P e e ence-based measu es o heal h ela ed quali y o li e in congeni al mobili y impai men : A sys ema ic e iew o alidi y and esponsi eness Heal h Economics Re iew P o ided in Coope a ion wi h: Sp inge Na u e Sugges ed Ci a ion: B ay, Na han; Spence , Llinos Ha ; Edwa ds, Rhiannon Edwa ds (2020) : P e e ence-based measu es o heal h ela ed quali y o li e in congeni al mobili y impai men : A sys ema ic e iew o alidi y and esponsi eness, Heal h Economics Re iew, ISSN 2191-1991, Sp inge , Heidelbe g, Vol. 10, Iss. 9, pp. 1-38, h ps://doi.o g/10.1186/s13561-020-00270-3 This Ve sion is a ailable a : h ps://hdl.handle.ne /10419/285161 S anda d-Nu zungsbedingungen: Die Dokumen e au EconS o dü en zu eigenen wissenscha lichen Zwecken und zum P i a geb auch gespeiche und kopie we den. Sie dü en die Dokumen e nich ü ö en liche ode komme zielle Zwecke e iel äl igen, ö en lich auss ellen, ö en lich zugänglich machen, e eiben ode ande wei ig nu zen. So e n die Ve asse die Dokumen e un e Open-Con en -Lizenzen (insbesonde e CC-Lizenzen) zu Ve ügung ges ell haben soll en, gel en abweichend on diesen Nu zungsbedingungen die in de do genann en Lizenz gewäh en Nu zungs ech e. Te ms o use: Documen s in EconS o may be sa ed and copied o you pe sonal and schola ly pu poses. You a e no o copy documen s o public o comme cial pu poses, o exhibi he documen s publicly, o make hem publicly a ailable on he in e ne , o o dis ibu e o o he wise use he documen s in public. I he documen s ha e been made a ailable unde an Open Con en Licence (especially C ea i e Commons Licences), you may exe cise u he usage igh s as speci ied in he indica ed licence. h ps://c ea i ecommons.o g/licenses/by/4.0/ REVIEW Open Access P e e ence-based measu es o heal h- ela ed quali y o li e in congeni al mobili y impai men : a sys ema ic e iew o alidi y and esponsi eness Na han B ay 1,2* , Llinos Ha Spence 1,2 and Rhiannon Tudo Edwa ds 1,2 Abs ac In oduc ion: Mobili y impai men is he leading cause o disabili y in he UK. Indi iduals wi h congeni al mobili y impai men s ha e unique expe iences o heal h, quali y o li e and adap a ion. P e e ence-based ou comes measu es a e o en used o help in o m decisions abou heal hca e unding and p io i isa ion, howe e he applicabili y and accu acy o hese measu es in he con ex o congeni al mobili y impai men is unclea . Inaccu a e ou come measu es could po en ially a ec he ca e p o ided o hese pa ien g oups. The aim o his sys ema ic e iew was o examine he pe o mance o p e e ence-based ou come measu es o he measu emen o u ili y alues in a ious o ms o congeni al mobili y impai men . Me hods: Ten da abases we e sea ched, including Science Di ec , CINAHL and PubMed. Sc eening o e e ence lis s and hand-sea ching we e also unde aken. Desc ip i e and na a i e syn heses we e conduc ed o combine and analyse he a ious indings. Resul s we e g ouped by condi ion. Ou come measu e pe o mance indica o s we e adap ed om COSMIN guidance and we e g ouped in o h ee b oad ca ego ies: alidi y, esponsi eness and eliabili y. Sc eening, da a ex ac ion and quali y app aisal we e ca ied ou by wo independen e iewe s. Resul s: A o al o 31 s udies we e conside ed eligible o inclusion in he sys ema ic e iew. The as majo i y o s udies ela ed o ei he ce eb al palsy, spina bi ida o childhood hyd ocephalus. O he ele an condi ions included muscula dys ophy, spinal muscula a ophy and congeni al club oo . The mos commonly used p e e ence-based ou come measu e was he HUI3. Repo ing o pe o mance p ope ies p edominan ly cen ed a ound cons uc alidi y, h ough known g oup analyses and assessmen o con e gen alidi y be ween compa able measu es and di e en ypes o esponden s. A small numbe o s udies assessed esponsi eness, bu assessmen o eliabili y was no epo ed. Inc eased clinical se e i y appea s o be associa ed wi h dec eased u ili y ou comes in congeni al mobili y impai men , pa icula ly in e ms o g oss mo o unc ion in ce eb al palsy and lesion le el in spina bi ida. Howe e , p e e ence-based measu es exhibi limi ed co ela ion wi h a ious o he condi ion-speci ic and clinically ele an ou come measu es. (Con inued on nex page) © The Au ho (s). 2020 Open Access This a icle is licensed unde a C ea i e Commons A ibu ion 4.0 In e na ional License, which pe mi s use, sha ing, adap a ion, dis ibu ion and ep oduc ion in any medium o o ma , as long as you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons licence, and indica e i changes we e made. The images o o he hi d pa y ma e ial in his a icle a e included in he a icle's C ea i e Commons licence, unless indica ed o he wise in a c edi line o he ma e ial. I ma e ial is no included in he a icle's C ea i e Commons licence and you in ended use is no pe mi ed by s a u o y egula ion o exceeds he pe mi ed use, you will need o ob ain pe mission di ec ly om he copy igh holde . To iew a copy o his licence, isi h p://c ea i ecommons.o g/licenses/by/4.0/. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed in a c edi line o he da a. * Co espondence: [email p o ec ed] 1 School o Heal h Sciences, F on Heulog, Bango Uni e si y, Gwynedd LL57 2EF, Wales, UK 2 Cen e o Heal h Economics and Medicines E alua ion, A dudwy, Bango Uni e si y, Gwynedd LL57 2PZ, Wales, UK B ay e al. Heal h Economics Re iew (2020) 10:9 h ps://doi.o g/10.1186/s13561-020-00270-3 (Con inued om p e ious page) Conclusion: P e e ence-based measu es exhibi impo an issues and disc epancies ela ing o alidi y and esponsi eness in he con ex o congeni al mobili y impai men , hus ca e mus be aken when u ilising hese measu es in condi ions associa ed wi h congeni al mobili y impai men s. Keywo ds: Disabili y, Mobili y impai men , Quali y o li e, Heal h- ela ed quali y o li e, Pa ien epo ed ou comes, P e e ence-based ou come measu es, U ili ies, QALYs In oduc ion Mobili y impai men and assis i e mobili y echnology Mobili y impai men is he leading cause o disabili y in he UK, accoun ing o 52% o epo ed disabili ies [1]. Mobili y impai men s a ise om a as a ay o di e en disabili ies, condi ions, inju ies and illnesses. Howe e , hey can be classi ied b oadly as ei he congeni al (i.e. om bi h) o acqui ed (i.e. occu ing la e in li e). Whe he a disabili y is p esen om bi h o acqui ed la e on in li e signi ican ly in luences indi idual adap a- ion. Fo ins ance, indi iduals wi h congeni al disabili ies exhibi highe deg ees o li e sa is ac ion, sel -iden i y and sel -e icacy ( ela ed o hei disabili y) han indi id- uals who ha e had o adap o acqui ed disabili y [2]. Adap a ion o disabili y is in luenced by sel -concep and disabili y iden i y, which in u n a e ela ed o he onse o disabili y [2]. Common congeni al condi ions which can impac mo- bili y include ce eb al palsy (CP) and spina bi ida (SB). CP e e s o a numbe o condi ions caused by damage o he pa s o he b ain which con ol mo emen , bal- ance and pos u e, and can be caused ei he by abno mal b ain de elopmen o auma. CP is symp omized by a ying deg ees o pe manen mo emen diso de , in- cluding poo coo dina ion, muscle s i ness/weakness and in olun a y mo emen s. SB a ec s he de elopmen o he spine and spinal co d be o e bi h, and can esul in leg weakness and pa alysis. The e a e h ee ypes o SB: myelomeningocele, meningocele and SB occul a. Bo h congeni al and acqui ed mobili y impai men s may necessi a e he use o assis i e echnology o alle i- a e impai men s. Assis i e echnology e e s o a wide a ay o p oduc s and se ices which enhance unc ion- ing, pa icipa ion and p omo e independence o people who ha e disabili ies. The Medicines and Heal hca e P oduc s Regula o y Agency de ines assis i e echnology as any de ice “in ended o compensa e o o alle ia e an inju y, handicap o illness o o eplace a physical unc- ion”[3]. Assis i e echnology, such as wheelchai s, a e an “essen ial componen o inclusi e sus ainable de el- opmen ”[4], and can enhance he undamen al eedoms and equali y o oppo uni y o people wi h mobili y im- pai men s and o he disabili ies. The Uni ed Na ions (UN) s a es ha access o app op ia e and a o dable as- sis i e echnology is a basic human igh [5]; he UN Con en ion on he Righ s o Pe sons wi h Disabili ies has been a i ied by 175 Membe S a es, who a e obli- ga ed o ensu e ha a o dable assis i e echnology is a ailable o all indi iduals in need. Howe e , The Wo ld Heal h O ganiza ion (WHO) es ima es ha only 10% o people who need assis i e echnology ha e access o i [6], and he e emain pe sis en challenges in he equi - able p o ision o assis i e echnology, pa icula ly in de- eloping coun ies. One o he keys issues is in assessing he cos s and bene i s o di e en assis i e echnologies, and de eloping e idence-based app oaches o p o ision which make bes use o limi ed esou ces o maximise he ou comes o people wi h disabili ies. The Na ional Heal h Se ice (NHS) in he UK spends almos £200million pe yea on wheelchai s alone [7], hus he e is an impe a i e o ensu e ha assis i e mo- bili y echnologies (AMTs) such as wheelchai s and o he mobili y-enhancing in e en ions a e p o ided in an e idence-based manne , u ilising e idence o cos - e ec i eness o guide se ice commissioning. Economic e alua ion and quali y-adjus ed li e yea s Me hods o economic e alua ion a e now ou inely em- bedded in he e alua ion o heal h echnologies, and used o es ima e he cos o inc emen al bene i s associ- a ed wi h new and al e na i e heal h in e en ions. Cos - u ili y analysis, speci ically es ima ion o cos pe quali y- adjus ed li e yea s (QALYs), has become he p edomin- an o m o economic e alua ion o new heal h ech- nologies in he UK, in pa due o he Na ional Ins i u e o Heal h and Ca e Excellence’s (NICE) ad ocacy o his app oach [8]. The QALY amewo k has become in- c easingly in luen ial in heal h policy as a heo e ically uni e sal and gene ic app oach o measu ing bene i s ia a single common ou come. In o de o calcula e QALYs, heal h s a e u ili y alues a e needed. These alues a e mos commonly de i ed om p e e ence-based measu es (PBMs) o heal h- ela ed quali y o li e (HRQoL). HRQoL is a subjec i e and mul i-dimensional cons uc de ined as he pe - cei ed impac o heal h s a us on quali y o li e, includ- ing physical, psychological and social unc ioning. PBMs o HRQoL a e used o assess he social desi abili y and u ili y alues associa ed wi h di e en s a es o heal h. B ay e al. Heal h Economics Re iew (2020) 10:9 Page 2 o 38 As he desc ip i e sys ems and alue se s o gene ic PBMs a e usually de i ed om adul samples o he gen- e al popula ion, a common c i icism is ha hei gene - ici y limi s ele ance and sensi i i y in ce ain condi ions [9]. Mo eo e , in heal h s a es whe e quali y o li e akes p eceden o e quan i y o li e (e.g. ch onic illness, li e- limi ing condi ions and disabili y), QALYs de i ed om gene ic PBMs can de alue he e ec i eness o an in e - en ion [10]. Use o p e e ence-based measu es in he con ex o mobili y impai men The accu acy o a QALY es ima e is subjec o he sensi- i i y and applicabili y o he measu emen ool used o gene a e he u ili y da a. PBMs ha e been ound o be in- consis en in bo h congeni al and acqui ed mobili y im- pai men s [11–13], u he mo e di e en PBMs p oduce signi ican ly di e en esul s o AMT use s [14,15]. P e ious esea ch shows ha pa ien s wi h congeni al mobili y impai men s do no necessa ily conside mobil- i y o ha e a majo impac on hei HRQoL when sui - able adap a ions (such as AMT) a e a ailable [16,17]. Howe e , gene al popula ion PBM alue se s hea ily im- pac es ima ion o HRQoL when abili y o walk is a - ec ed. As an example, using he NICE app o ed UK alue se o he Eu oQoL i e-dimension ( h ee le el e sion) (EQ-5D-3 L), he lowes possible mobili y le el (‘con ined o bed’) has a disu ili y o −0.664, meaning ha an indi idual who is unable o walk bu is o he wise mobile using AMT can achie e a maximum u ili y alue o 0.336 (0 = dea h; 1 = pe ec heal h), e en i hey ha e no o he HRQoL impac s. This aises he ques ions as o whe he exis ing PBMs a e a alid sou ce o u ili y alues in mobili y impai ed popula ions, pa icula ly AMT use s. The alidi y o PBMs can be es ed by compa ing e- sul s ac oss g oups o pa ien s and by compa ing gene ic PBMs wi h condi ion-speci ic measu es. Fo ins ance, he EQ-5D-3 L and he Heal h Assessmen Ques ion- nai e (HAQ; an ou come measu e o heuma oid a h- i is) bo h measu e heal h s a us in signi ican ly di e en ways [18], sugges ing ha he EQ-5D-3 L is lacking con- side a ion o impo an heal h impac s associa ed wi h heuma oid a h i is. These issues a e pa ly due o he insensi i i y o he EQ-5D-3 L ‘mobili y’dimension o accu a ely assess he a ied impac s o heuma oid a h- i is on mobili y [19]. Simila ly, he limi ed le el choices on he EQ-5D-3 L ha e been ound o cause some indi- iduals wi h mobili y impai men s o choose le els which a e mo e o less se e e han hei ac ual s a e, such as using ‘I am con ined o bed’ o subs i u e being con ined ‘ o an elec ic wheelchai ’[20]. The upda ed i e le el e sion o he EQ-5D (EQ-5D-5 L) is unlikely o add ess his issue as he i e le el choices s ill ocus on walking and do no ake accoun o al e na i e me hods o mobili y. E en simple gene ic measu es o heal h s a us, such as he single ques ion sel - epo ed heal h (SRH) scale (i.e. “in gene al, would you say you heal h is excellen , e y good, good, ai , o poo ?”), exhibi only limi ed co el- a ion wi h PBMs such as he Heal h U ili ies Index (HUI) 3 and Assessmen o Quali y o Li e (AQoL) in he con ex o SB [21] and CP [22]. Likewise, o indi id- uals wi h spinal co d inju ies, he wo ding o he 36- I em Sho Fo m Heal h Su ey (SF-36) ( om which he Sho -Fo m Six-Dimension (SF-6D) PBM is calcula ed) mus be modi ied in o de o main ain ele ance [23]. Conside ing he po en ial issues o using gene ic PBMs in disabili y, and congeni al mobili y impai men speci - ically, i is appa en ha he e a e a numbe o impo - an conside a ions when using PBMs o e alua e AMT in e en ions and o he mobili y-enhancing in e en- ions o people wi h congeni al mobili y impai men s. The objec i e o his sys ema ic e iew is he e o e o examine he measu emen p ope ies o gene ic u ili y- based PBMs in a ious o ms o congeni al mobili y im- pai men . All e idence epo ing (o in e ing) he alid- i y, eliabili y and/o esponsi eness o PBMs in condi ions associa ed wi h congeni al mobili y impai - men was colla ed and syn hesised. Compa able condi ion-speci ic e iews o PBM pe o mance ha e been conduc ed in mobili y impai men s such as heuma oid a h i is [24], CP [25] and mul iple scle osis [26], howe e PBM pe o mance has no been sys ema - ically summa ised and colla ed ac oss a ange o con- geni al mobili y impai men s o da e. Me hods This sys ema ic e iew ollowed he Uni e si y o Yo k Cen e o Re iews and Dissemina ion (CRD) p inciples o conduc ing sea ches and ex ac ing da a [27]. In e - ne e e ence da abase sea ching was he main s a egy o ga he ing e idence. Da abases included: Coch ane Collabo a ion Regis e and Lib a y, Science Di ec , CINAHL, ASSIA, PsychINFO, PubMed and Web o Sci- ence. Sc eening o e e ence lis s, hand-sea ching and a ge ed sea ching ia he CRD da abase (which co e s he Da abase o Abs ac s o Re iews o E ec s (DARE), he NHS Economic E alua ion Da abase (NHS EED) and he Heal h Technology Associa ion (HTA) da abase) we e ca ied ou in addi ion o he p ima y da abase sea ches. Due o limi ed ansla ion esou ces, only s ud- ies w i en o ansla ed in o English o Welsh we e eli- gible o inclusion. Sea ch esul s we e managed using he online bibliog aphic managemen so wa e Re wo ks ( o s o age o i les om he sys ema ic sea ches) and Mendeley ( o e e encing pu poses). The sys ema ic B ay e al. Heal h Economics Re iew (2020) 10:9 Page 3 o 38 e iew p o ocol was egis e ed on PROSPERO (CRD42018088932). Sea ch e ms Fo he pu pose o his e iew, mobili y impai men was de ined as any congeni al (i.e. p esen om o sho ly a e bi h) condi ion, impai men , disabili y o illness which causes signi ican es ic ions o mobili y o 12 mon hs o longe , and which necessi a es he use o AMT, su ge y o ehabili a ion o main ain, acili a e o subs i u e ambula- ion, o o educe complica ions ela ed o mobili y im- pai men . Acqui ed mobili y impai men s (i.e. no p esen om bi h) and sho - e m inju ies, such as sp ains o acu e muscula inju ies, we e no included unde his de - ini ion o mobili y impai men . Sea ch e ms included a mix u e o MeSH (Medical Subjec Heading) and non-MeSH wo ds and ph ases, di- ided in o wo g oups: ‘popula ion’and ‘ou comes’(see Table 1). In o de o iden i y s udies e e ing o in e en ions a- he han pa ien g oups (e.g. s udies examining ‘wheel- chai use s’mo e gene ally), he ‘popula ion’sea ch e ms also co e ed ele an AMTs and mobili y-enhancing in- e en ions. The ‘ou comes’sea ch e ms co e ed ele an PBM keywo ds, including speci ic ou come measu es (such as he a ious e sions o he EQ-5D and HUI mea- su es). An NHS pos u e and mobili y se ice manage was consul ed o e ine he sea ch e ms. An example o a sea ch s ing is shown in Table 2. S udy eligibili y Any s udy epo ing he pe o mance o PBMs o HRQoL in pa ien g oups wi h congeni al mobili y im- pai men s was eligible o inclusion. This included s ud- ies epo ing p oxy ou comes. The e was no es ic ion on s udy ype. S udies ocussing solely on non-PBMs o HRQoL o acqui ed mobili y impai men s we e ex- cluded. S udies which included pa ien g oups wi h a y- ing deg ees o disabili y/disease se e i y we e conside ed o inclusion i he majo i y o pa ien s had a congeni al mobili y impai men o i he da a o pa ien s wi h con- geni al mobili y impai men s was epo ed sepa a ely (i.e. sub-g oup analysis). Sc eening Two esea che s unde ook each s age o he sc eening p ocess. Fo he ini ial sc eening p ocess, all iden i ied s udies we e assessed o ele ance based on hei i le and desc ip o e ms, he emaining s udies we e hen assessed by hei abs ac . All s udies conside ed ele an a e he ini ial sc eening p ocess we e hen ob ained in ull. Bo h e iewe s sc eened each s udy independen ly. A hi d esea che was consul ed when he e was dis- ag eemen abou he inclusion o a speci ic s udy. Quali y app aisal All ele an s udies which me he ini ial inclusion c i- e ia we e c i ically app aised o me hodological quali y by wo esea che s. Quali y app aisal me hods we e adap ed om simila sys ema ic e iews in o he clinical a eas [28–30]. Quali y app aisal was no used o exclude s udies, bu o illus a e he o e all quali y o esea ch conduc ed in his opic a ea. Quali y app aisal ocussed on six key a eas: Whe he es s o s a is ical signi icance we e ca ied ou Di e ences be ween in e en ions and/o pa ien g oups (i.e. sub-g oup analysis) Clinical signi icance and ele ance o esul s Repo ing o missing da a Response and comple ion a es Explici epo ing o inclusion/exclusion c i e ia Da a ex ac ion Da a ex ac ion c i e ia included: S udy cha ac e is ics: s udy ype, coun y, numbe / composi ion o s udy g oups, missing da a Demog aphics: numbe o pa icipan s, age, gende , ype/se e i y o mobili y impai men Measu es: Gene ic PBMs used, condi ion-speci ic measu es used, o he clinically ele an measu es used Ou comes: Mean u ili y sco es, mean u ili y sco es o ele an sub-g oups, s a is ical signi icance be ween g oups Pe o mance: Known g oup analyses, con e gen alidi y (co ela ion be ween ou comes and/o esponden ypes), esponsi eness, eliabili y, esponse/comple ion a es Analysis o he pe o mance o p e e ence-based measu es PBM pe o mance indica o s we e adap ed om COS- MIN measu emen p ope y guidance o heal h- ela ed pa ien - epo ed ou comes [31]. Assessmen o alidi y In his con ex alidi y e e s o he ex en o which a PBM can be conside ed o measu e wha i has been de- signed o measu e (i.e. HRQoL), and whe he i does so in a sys ema ic manne . By es ablishing whe he a spe- ci ic PBM is su icien ly alid in a pa icula pa ien g oup, g ea e con idence can be placed in he gene a ed da a. We ocussed p edominan ly on cons uc alidi y in his e iew. Cons uc alidi y was assessed in a numbe o ways. Fi s ly, known-g oup analyses we e used o assess B ay e al. Heal h Economics Re iew (2020) 10:9 Page 4 o 38 whe he speci ic PBMs we e able o de ec expec ed di - e ences be ween di e en pa ien g oups (i.e. a iance due o se e i y o illness). Secondly, con e gen alidi y was de e mined by examining co ela ion be ween com- pa able ou comes, o ins ance be ween PBMs and condi ion-speci ic measu es wi h compa able cons uc s. Finally, con e gen alidi y was u he examined by looking a co ela ion be ween esponden s ypes (i.e. sel - epo ed and p oxy u ili y ou comes). In he in e es o uni o mi y, he s eng h o co ela ions was de ined as absen ( < 0.20), weak ( = 0.20 o 0.35), mode a e ( = 0.35 o 0.50) and s ong ( ≥0.50) [32]. Assessmen o eliabili y Reliabili y e e s o he eplicabili y o esul s. Reliabili y is commonly assessed by examining es - e es esul s and in e - a e eliabili y o PBMs in de ined unchanging pa ien g oups. Table 1 Sea ch e ms and ph ases Popula ion Ou comes Assis ed mobili y Mobili y scoo e 15D Assis i e mobili y Mobili y echnolog* AQoL B ain damage* Mo o dis* Assessmen o Quali y o Li e B ain inju * Mo o ised scoo e Child heal h u ili ies Buggy Neu odisabili y Child heal h u ili y Calipe Neu ological dis* CHU9D Cane Neu omo o dis* CHU-9D Ce eb al palsy Neu omuscula dis* EQ 5D Club oo O ho i* EQ-5D Club oo Os eogenesis impe ec a Eu oQoL C u ch* Pa aly* Heal h u ili ies Diplegi* Pa aplegi* Heal h-u ili ies Dysmelia Physical disab* HUI Dys oph* Physical impai * HUI2 Elec ic chai Physically disab* HUI3 Elec ic powe ed indoo ou doo chai Physically impai ed P e e ence based Elec ic powe ed indoo /ou doo chai Powe chai P e e ence-based Elec ic scoo e Powe ed chai QALY Elec ically powe ed indoo ou doo chai Pushchai Quali y adjus ed li e yea Elec ically powe ed indoo /ou doo chai Quad iplegi* Quali y-adjus ed li e yea Elec onically powe ed indoo ou doo chai Rolla o Quali y o well-being scale Elec onically powe ed indoo /ou doo chai Scoo e QWB-SA *encephal* Spina bi ida Sho Fo m Six Dimension EPIOC Spinal muscula a ophy Sho F om 6 Dimension Func ional disab* Talipes SF6D Handicap* Te aplegi* SF-6D Hemiplegi* Walk aid Hyd ocephalus Walk-aid Knee scoo e Walke Knee walke Walking aid Mobili y aid Walking ame Mobili y de ice Walking s ick Mobili y dis* Walking-aid Mobili y equipmen Wheelchai Mobili y impai * * Indica es unca ed wo ds/ph ases B ay e al. Heal h Economics Re iew (2020) 10:9 Page 5 o 38 Assessmen o esponsi eness Responsi eness e e s o he ex en o which a measu e can iden i y changes in heal h s a us [28]. A esponsi e measu e should be able o de ec clinically signi ican changes in heal h ou comes o e ime [29]. Responsi e- ness was de e mined by examining he ela ionship be- ween ou comes de i ed om PBMs and o he ele an measu es, be o e and a e an in e en ion. E idence syn hesis Desc ip i e syn hesis o sea ch esul s was conduc ed [27] and p esen ed in abula ed o m. Na a i e syn hesis was unde aken o de elop a s uc u ed na a i e o e- sul s; ex ac ed esul s we e g ouped by ype o mobili y impai men and ca ego y o PBM pe o mance. Resul s See Fig. 1 o sea ch ou comes and he sc eening p ocess lowcha . Sea ches we e conduc ed om Ma ch o May 2018. In o al 1489 s udy a icles we e iden i ied: 1332 om he bibliog aphic sea ches and 157 a icles om o he sou ces (i.e. CRD da abase, sc eening o e e ence lis s and hand-sea ching), o which 410 duplica es we e emo ed. A e sc eening o i les and abs ac s, 66 Table 2 Example o keywo d sea ch s ing (“Assis ed mobili y”O “Assis i e mobili y”O “B ain damage*”O “B ain inju *”O Buggy O Calipe O Cane O “Ce eb al palsy”O “Club oo ” O Club oo O C u ch* O Diplegi* O Dysmelia O Dys oph* O “Elec ic chai ”O “Elec ic powe ed indoo ou doo chai ”O “Elec ic powe ed indoo /ou doo chai ”O “Elec ic scoo e ”O “Elec ically powe ed indoo ou doo chai ”O “Elec ically powe ed indoo /ou doo chai ”O “Elec onically powe ed indoo ou doo chai ”O “Elec onically powe ed indoo /ou doo chai ”O encephal* O EPIOC O “Func ional disab*”O Handicap* O Hemiplegi* O Hyd ocephalus O “Knee scoo e ”O “Knee walke ”O “Mobili y aid”O “Mobili y de ice”O “Mobili y dis*”O “Mobili y equipmen ”O “Mobili y impai *”O “Mobili y scoo e ”O “Mobili y echnolog*”O “Mo o dis*”O “Mo o ised scoo e ” O Neu odisabili y O “Neu ological dis*”O “Neu omo o dis*”O “Neu omuscula dis*”O O ho i* O “Os eogenesis impe ec ”O Pa aly* O Pa aplegi* O “Physical disab*”O “Physical impai *”O “Physically disab*”O “Physically impai ed”O “Powe chai ”O “Powe ed chai ”O Pushchai O Quad iplegi* O Rolla o O Scoo e O “Spina bi ida”O “Spinal muscula a ophy”O Talipes O Te aplegi* O “Walk aid”O “Walk-aid”O Walke O “Walking aid”O “Walking ame”O “Walking s ick”O “Walking-aid”O Wheelchai ) AND (15D OR AQoL OR “Assessmen o Quali y o Li e”OR “Child heal h u ili ies”OR “Child heal h u ili y”OR CHU9D OR “CHU-9D”OR EQ. 5D OR “EQ-5D”OR Eu oQoL OR “Heal h u ili ies”OR “Heal h-u ili ies”OR HUI OR HUI2 OR HUI3 OR “P e e ence-based”OR “P e e ence based”OR QALY OR “Quali y adjus ed li e yea ”OR “Quali y o well-being scale”OR “Quali y-adjus ed li e yea ”OR “QWB-SA”OR “Sho Fo m Six Dimension”OR “Sho F om 6 Dimension”OR SF6D OR “SF-6D”) Fig. 1 PRISMA lowcha o sea ch ou comes and sc eening p ocess B ay e al. Heal h Economics Re iew (2020) 10:9 Page 6 o 38 s udies we e iden i ied as po en ially eligible. Following ull e iew o ull- ex s, 35 s udies we e excluded o a a ie y o easons (see Fig. 1). In o al 31 s udies we e iden i ied as ele an and eligible o inclusion in he sys- ema ic e iew. Quali y app aisal ou comes a e p esen ed in Table 3. S udy and pa ien cha ac e is ics S udy and pa icipan cha ac e is ics a e p esen ed in Table 4. Mos o he s udies (22 o 31) we e c oss- sec ional s udies [15,21,22,34,36–38,40–45,47–52, 54,58,59], six we e p ospec i e coho s udies [33,35, 39,46,53,57], wo we e case-con ol s udies [11,56] and one was a andomised con olled ial [55]. The se- lec ed s udies we e conduc ed in a ange o di e en coun ies; mos we e (n= 15) om Canada [21,22,33, 35,36,38–43,46,49,53,57]. The sample sizes o ele- an s udy g oups anged om 13 [15] o 770 [44]. Fou een s udies included da a ela ing o CP [22,33, 35,36,39,46,48–51,53,55,57,58], six included da a ela ing o SB [21,38,51,52,54,56] and i e included da a ela ing o childhood hyd ocephalus [40–43,45]. Da a o a ange o o he ele an condi ions we e also ound in ei he single s udies o om ex ac able sub- g oups, hese included muscula dys ophy [34,44], spinal muscula a ophy [47], Mo quio A synd ome [37], congeni al club oo [59] and mic ocephaly [51]. Th ee s udies ocused on mul iple condi ions whe e sub-g oup da a could no be examined sepa a ely [11,15,51]. The as majo i y o s udies (23 o 31) included only child/adolescen pa icipan s [11,15,33,35,36,38–44, 46–54,56,58]. O he emaining s udies, six included child en/adolescen s and adul s [21,22,34,37,55,57] and wo included only adul s [45,59]. PBM epo ing was p edominan ly om p oxies (13 o 23 s udies); ele en s udies included bo h sel - epo ed and p oxy da a [15,21,22,36,43,48–50,53,54,57] and se en s udies included only sel - epo ed PBM da a [11,34,37, 45,55,58,59]. In e ms o use o PBMs, 22 o he s udies used a e - sion o he HUI [15,21,22,33,35,36,38–44,46,48,49, 51–54,56,57], eigh used a e sion o he EQ-5D [11, 15,34,37,47,50,58,59], h ee used a e sion o AQoL ins umen [21,22,57], one used he 15D [45] and one used he SF-6D [55]. Na a i e syn hesis U ili y ou comes a e p esen ed in Table 5and PBM pe - o mance ou comes a e p esen ed in Table 6. The na a- i e syn hesis is ca ego ised by ype o mobili y impai men and PBM pe o mance indica o . No s udies epo ed PBM eliabili y ou comes, he e o e eliabili y esul s ha e no been p esen ed. Ce eb al palsy Known-g oup analyses Fi e s udies epo ed known-g oup analyses in CP [22, 33,51,53,58]. Pe ou and Kupek [51] es ima ed ha he adjus ed HUI3 disu ili y o childhood CP om pe ec heal h was −0.72 (95% con idence in e al [CI] -0.61 o −0.85), and −0.65 (95% CI −0.54 o −0.78) om child- hood no ms. Two s udies ound ha as CP se e i y (i.e. g oss mo o unc ion) inc eased, a e age u ili y sco es (measu ed using HUI3 o AQoL) dec eased in adoles- cen s and young adul s wi h CP [22,53]; Rosenbaum e al. [53] ound s a is ically signi ican di e ences in mean u ili y sco es be ween mos G oss Mo o Func ion Classi ica ion Sys em (GMFCS) le els (p < 0.01). One s udy demons a ed ha he ision, pain and cogni ion dimensions o he HUI3 s eadily declined as GMFCS le el inc eased, howe e s a is ical signi icance was no epo ed [33]. Vi ale e al. [58] ound ha adolescen s wi h CP had signi ican ly highe a e age EQ-5D u ili y sco es (0.92) compa ed o adolescen s wi h scoliosis (wi h como bidi ies) (0.73; p> 0.05), al hough selec ion o hese pa ien sub-g oups was no explici ly jus i ied and he e sion o he EQ-5D was no epo ed. Con e gen alidi y: compa ing measu es Two s udies epo ed ha GMFCS le el was co ela ed wi h wo sening u ili y sco es [22,53]. Young e al. [22] ound ha GMFCS le el in childhood was esponsible o be ween 45% (AQoL: β=−0.148; p< 0.001) and 53% (HUI3: β=−0.205; p< 0.001) o a iance in u ili y sco es. Rosenbaum e al. [53] ound a s ong nega i e co ela ion be ween he HUI3 u ili y sco es o adoles- cen s wi h CP and hei GMFCS le el ( =−0.81). In e ms o indi idual PBM dimensions, esul s om ou s udies we e a ied [33,35,39,49]; Kennes e al. [39] ound ha he dimension mos associa ed wi h GMFCS le el in child en was ambula ion ( au-b = 0.82; p< 0.01). Ba le e al. [33] ound ha he HUI3 ision, pain and cogni ion dimensions gene ally wo sened as GMFCS le el inc eased in adolescen s; howe e , he e was no in- dica ion ha hese dimensions we e de e minan s o mo o capaci y decline. Two s udies [35,49] epo ed a signi ican nega i e associa ion be ween he HUI3 pain dimension and GMFCS le el in child en wi h CP, how- e e bo h o hese s udies only examined he HUI3 pain dimension and no he ull HUI3 sys em. Th ee s udies epo ed a ious le els o co ela ion be- ween PBMs and o he ou come measu es in CP [22,46, 53]. Young e al. [22] ound mode a e co ela ion be- ween u ili y sco e and SRH ( = 0.41; p< 0.001 o bo h he HUI3 and AQoL). Two s udies compa ed he Qual- i y o Li e Ins umen o People wi h De elopmen al Disabili ies (QOL Ins umen ) and he HUI3 [46,53]; Rosenbaum e al. [53] epo ed ha adolescen s’HUI3 B ay e al. Heal h Economics Re iew (2020) 10:9 Page 7 o 38 u ili y sco es explained be ween 3% (belonging) and 14% (being) o a iance in QOL Ins umen dimension sco es, while Li ings on and Rosenbaum [46] epo ed ha he HUI3 and QOL Ins umen sha ed up o 23% a iance, hus he ela ionship be ween he measu es was conside ed o be mode a e a bes . Two s udies epo ed on he ela ionship be ween di e en PBMs in CP [22,57]. Al hough u ili y sco es de i ed om he HUI3 and AQoL we e s ongly co - ela ed ( = 0.87; p< 0.001) [22], HUI3 de i ed u ili y sco es ended o be lowe han AQoL de i ed u ili y sco es [22,57]. Con e gen alidi y: compa ing esponden s Fou s udies examined co ela ion be ween esponden s in CP [22,48–50]. Mo ow e al. [48] epo ed mode a e ag eemen be ween pa en s and doc o s o child en wi h CP o he HUI2/3 dimensions o sensa ion (63.6% ag eemen ; Kappa 0.41), cogni ion (70% ag eemen ; Kappa 0.56), sel -ca e (100% ag eemen ; Kappa 1.00) and ambula ion (63.6% ag eemen ; Kappa 0.46). Good co el- a ion was also ound be ween child sel - epo ed HUI3 pain sco es and equi alen pa en p oxy sco es (Good- man and K uskal’s y s a is ic = 0.57; p< 0.001) [49]. Pe ez Sousa e al. [50] epo ed a high le el o dis- ag eemen be ween pa en s and child en on he EQ-5D Table 3 Quali y app aisal ou comes S udy e e ence (au ho , yea ) Tes s o s a is ical signi icance conduc ed Sub-g oup analyses conduc ed Clinical implica ions discussed P opo ions o missing/inco ec da a epo ed Response and/o comple ion a es epo ed Inclusion and/o exclusion c i e ia explici ly s a ed Ba le e al. (2010) [33]YYYYXY B ay e al. (2017) [15]YYYYYY Bu s om e al. (2014) [11]YYXYYX Ca azza e al. 2016 [34]XXXXXX Ch is ensen e al. (2016) [35]YYYXYX Findlay e al. (2015) [36]YYYYYX Hend iksz e l al (2014) [37]. YYYYXY Ka mu and Kulka ni (2018) [38]YXYYXX Kennes e al. (2002) [39]YYYYXY Kulka ni e al. (2004) [40]YXYXYY Kulka ni (2006) [41]YYXYXY Kulka ni e al. (2008) [42]YXYYYX Kulka ni e al. (2008) [43]YYYXYY Land eld e al. (2016) [44]YXYXYX Lindquis e al. (2014) [45]YYYXXY Li ings on and Rosenbaum (2008) [46]YXYYXX Lopez-Bas ida e al. (2017) [47]XXYYXX Mo ow e al. (2011) [48]. YYYXYY Penne e al. (2013) [49]YYYXYX Pe ez Sousa e al. (2017) [50]YYYYYY Pe ou and Kupec (2009) [51]YYYYXY Rocque e al. (2015) [52]YYYXXY Rosenbaum e al. (2007) [53]YYYYXY Sims-Williams e al. (2016) [54]YYYYXY Slaman e al. (2015) [55]YXYXXY Til o d e al. (2005) [56]YXYXYX Usuba e al. (2014) [57]YYYYYY Vi ale e al. (2001) [58]YYYXXY Wallande e al. (2009) [59]. YXYXYY Young e al. (2010) [22]. YYYYYY Young e al. (2013) [21]YYYXYY B ay e al. Heal h Economics Re iew (2020) 10:9 Page 8 o 38 Table 5 Summa y o u ili y ou comes o included s udies S udy e e ence Condi ion(s) o in e es Responden ype PBM (s) O he ele an ou come measu es O e all u ili y sco es (mean ± SD) Sub-g oup u ili y sco es (mean ± SD) Ba le e al. (2010) [33] Adolescen s wi h ce eb al palsy P oxy (pa en ) HUI3 G oss Mo o Func ion Measu e 66 I ems (GMFM-66) Spinal Alignmen and Range o Mo ion Measu e (SAROMM) NA O e all u ili y sco es no epo ed, only ision, cogni ion and pain dimensions used - ambula ion, hea ing, speech, dex e i y and emo ion dimensions all excluded due o concep ual o e lap wi h o he measu es NA B ay e al. (2017) [15] Child en and adolescen s wi h impai ed mobili y ( ele an condi ions: ce eb al palsy, hemiplegia, muscula dys ophy) Sel - epo ed and p oxy (pa en ); ma ched-pai s HUI2, HUI3 and EQ-5D-Y Visual analogue scale (VAS) Child sel - epo ed HUI2: 0.53 (±0.07) HUI3: 0.22 (±0.09) EQ-5D-Y: 0.24 (±0.30) Pa en p oxy HUI2: 0.49 (±0.09) HUI3: 0.16 (±0.10) EQ-5D-Y: 0.01 (±0.14) NA Bu s om e al. (2014) [11] Child en and adolescen s wi h unc ional mo o , o hopaedic and medical disabili ies ( ele an condi ions: a og yposis mul iple congeni al, myelomeningocele, ce eb al palsy, o hopaedic lowe limb de o mi ies, achond oplasia) Sel - epo ed EQ-5D-Y VAS KIDSCREEN-27 KIDSCREEN-10 Sel - a ed heal h (SRH) Li e sa is ac ion ladde (LSL) NA O e all u ili y sco es no epo ed, only dimension sco es epo ed NA Ca azza e al. (2016) [34] Adolescen s and adul s wi h Duchenne muscula dys ophy Sel - epo ed EQ-5D-Y VAS Ba hel Index Mean 0.24 Va ied by coun y, anging om −0.71 (±0.41) in Sweden o 0.66 (±0.08) in Bulga ia NA Ch is ensen e al. (2016) [35] Child en and adolescen s wi h ce eb al palsy P oxy (ca egi e ) HUI3 Wong-Bake FACES Pain Ra ing Scale NA O e all u ili y sco es no epo ed, only HUI3 pain dimension measu ed NA Findlay e al. (2015) [36] Child en wi h ce eb al palsy Sel - epo ed and p oxy (ca egi e ); p opo ion o p oxy da a no epo ed HUI3 DISABKIDS Ch onic Gene ic module (DCGM-37) DISABKIDS Smiley measu e (DSM) Wong-Bake FACES Pain Ra ing Scale NA O e all u ili y sco es no epo ed, only HUI3 pain dimension measu ed NA Hend iksz e al. (2014) [37] Child en and adul s wi h Mo quio A synd ome Sel - epo ed EQ-5D-5 L B ie Pain In en o y Sho Fo m (BPI-SF) Adolescen Pedia ic Pain Tool (APPT) NA O e all u ili y sco es no epo ed Child g oup: u ili y sco e by wheelchai use equency No use: 0.534 Occasional use: 0.664 Full- ime use: −0.180 Adul g oup: u ili y sco e by wheelchai use equency No use: 0.846 Occasional use: 0.582 Full- ime use: 0.057 Ka mu and Kulka ni (2018) [38] Child en and adolescen s wi h spina bi ida (myelomeningocele) and P oxy (ca egi e ) HUI2 and HUI3 ( e sion used o calcula e u ili y Hyd ocephalus Ou come Ques ionnai e (HOQ) 0.51 (±0.28) NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 15 o 38 Table 5 Summa y o u ili y ou comes o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Responden ype PBM (s) O he ele an ou come measu es O e all u ili y sco es (mean ± SD) Sub-g oup u ili y sco es (mean ± SD) shun ed hyd ocephalus sco es no s a ed) Kennes e al. (2002) [39] Child en wi h ce eb al palsy P oxy (ca egi e ) HUI3 Func ional Independence Measu e o Child en (WeeFIM) S eng h and Di icul ies Ques ionnai e (SDQ) Wide Range Achie emen Tes (WRAT) NA O e all u ili y sco es no epo ed, only dimension sco es epo ed NA Kulka ni e al. (2004) [40] Child en wi h hyd ocephalus P oxy (pa en ) HUI2 HOQ NA O e all u ili y sco es no epo ed NA Kulka ni e al. (2006) [41] Child en wi h hyd ocephalus P oxy (pa en ) HUI2 HOQ NA O e all u ili y sco es no epo ed NA Kulka ni e al. (2008) [42] Child en wi h hyd ocephalus P oxy (ca egi e ) HUI3 HOQ 0.58 (±0.32) NA Kulka ni e al. (2008) [43] Child en wi h hyd ocephalus Sel - epo ed and p oxy (ca egi e ); p oxy- epo ed HUI3 and HOQ, sel - epo ed cHOQ HUI3 Child-comple ed e sion o he HOQ (cHOQ) 0.71 (±0.27) NA Land eld e al. (2016) [44] Child en and adolescen s wi h Duchenne muscula dys ophy P oxy (ca egi e ); al hough pa ien s included in da a collec ion, only p oxy u ili y da a epo ed HUI ( e sion no s a ed) Pedia ic Quali y o Li e In en o y (PedsQL) neu omuscula module 3.0 NA O e all u ili y sco es no epo ed U ili y sco e by ambula o y s a us Ea ly ambula o y: 0.75 La e non-ambula o y: 0.15 Lindquis e al. (2014) [45] Adul s who expe ienced hyd ocephalus in in ancy Sel - epo ed 15D NA S udy g oup: 0.92 Con ol g oup: 0.95 Li ings on and Rosenbaum (2008) [46] Adolescen s wi h ce eb al palsy P oxy (pa en ) HUI3 Quali y o Li e Ins umen o People wi h De elopmen al Disabili ies (QOL Ins umen ) NA O e all u ili y sco es no epo ed NA Lopez-Bas ida e al. (2017) [47] Child en wi h spinal muscula a ophy P oxy (ca egi e ) EQ-5D-3 L VAS Ba hel Index 0.16 (±0.44) U ili y sco e by spinal muscula a ophy ype Type II spinal muscula a ophy sub-g oup: −0.01 (±0.35) Sco es o Type I and III no epo ed Mo ow e al. (2011) [48] Child en wi h ch onic condi ions ( ele an condi ion: ce eb al palsy) Sel - epo ed and p oxy (pa en and doc o ); ma ched g oups HUI2 and HUI3 NA NA O e all u ili y sco es no epo ed o ele an sub-g oup NA Penne e al. (2013) [49] Child en and adolescen s wi h ce eb al palsy Sel - epo ed and p oxy (pa en and physician); p oxy- epo ed HUI3 pain sco e, sel - epo ed Wong-Bake FACES Pain Scale HUI3 Wong-Bake FACES Pain Ra ing Scale NA O e all u ili y sco es no epo ed, only HUI3 pain dimension measu ed NA Pe ez Sousa e al. Child en and adolescen s Sel - epo ed and EQ-5D-Y VAS NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 16 o 38 Table 5 Summa y o u ili y ou comes o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Responden ype PBM (s) O he ele an ou come measu es O e all u ili y sco es (mean ± SD) Sub-g oup u ili y sco es (mean ± SD) (2017) [50] wi h ce eb al palsy p oxy (mo he and a he ); ma ched g oups O e all u ili y sco es no epo ed, only dimension sco es epo ed Pe ou and Kupek (2009) [51] Child en wi h childhood condi ions ( ele an condi ions: mic ocephaly, ce eb al palsy, spinal muscula a ophy, muscula dys ophy, spina bi ida) P oxy (ca egi e ) HUI3 NA Mean u ili y by condi ion Mic ocephaly: 0.141 Ce eb al palsy: 0.276 Muscula dys ophy o spinal muscula a ophy: 0.386 Spina bi ida: 0.452 NA Rocque e al. (2015) [52] Child en and adolescen s wi h spina bi ida Sel - epo ed and p oxy (ca egi e ); p edominan ly p oxy (11% sel - epo ed) HUI3 NA NA O e all u ili y sco es no epo ed U ili y sco e by ype o spina bi ida Myelomeningocele: 0.51 Closed spinal dys aphism: 0.77 U ili y sco e by ea men his o y No his o y o shun o CM-II decomp ession: 0.74 Shun bu no CM-II decomp ession: 0.49 Shun and CM-II decomp ession: 0.29 Rosenbaum e al. (2007) [53] Adolescen s wi h ce eb al palsy Sel - epo ed and p oxy (pa en ); p oxy- epo ed HUI3, 34% sel - epo ed QOL Ins umen HUI3 QOL Ins umen 0.42 (±0.41) U ili y sco e by GMFCS le el GMFCS I: 0.84 (±0.20) GMFCS II: 0.50 (±0.31) GMFCS III: 0.39 (±0.31) GMFCS IV: 0.16 (±0.26) GMFCS V: −0.08 (±0.23) Sims-Williams e al. (2017) [54] Child en wi h spina bi ida Sel - epo ed and p oxy (ca egi e ); ma ched pai s HUI3 VAS Child sel - epo ed 0.58 (95% CI 0.49–0.66) Ca egi e p oxy 0.55 (95% CI 0.47–0.63) NA Slaman e al. (2015) [55] Adolescen s and young adul s wi h ce eb al palsy Sel - epo ed SF-6D 36-I em Sho Fo m Su ey (SF-36) - SF-6D u ili y ou comes de i ed om SF-36 Baseline Con ol: 0.74 (±0.12) In e en ion: 0.75 (±0.10) 6 mon hs pos in e en ion Con ol: 0.77 (±0.12) In e en ion: 0.80 (±0.03) NA Til o d e al. (2005) [56] Child en wi h spina bi ida P oxy (ca egi e ) HUI2 Quali y o Well-Being scale (QWB) Case g oup: 0.55 (±0.24) U ili y by case g oup lesion le el Sac al lesion: 0.61 (±0.26) Lowe lumba lesion: 0.54 (±0.19) Tho acic lesion: 0.45 (±0.25) Gene al popula ion con ol g oup: 0.93 (±0.11) Usuba e al. (2014) [57] Adolescen s and adul s wi h ce eb al palsy Sel - epo ed and p oxy (unde ined); p edominan ly p oxy (40% sel - epo ed) HUI3 and AQoL SRH Baseline (bo h g oups) HUI3: 0.29 (±0.39) AQoL: 0.35 (±0.33) 8-yea ollow-up (bo h g oups) HUI3: 0.29 (±0.38) AQoL: 0.35 (±0.32) NA Vi ale e al. (2001) [58] Adolescen s wi h o hopaedic p oblems ( ele an condi ion: ce eb al palsy) Sel - epo ed EQ-5D ( e sion no s a ed) SF-36 Ce eb al palsy sub-g oup: 0.922 NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 17 o 38 Table 5 Summa y o u ili y ou comes o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Responden ype PBM (s) O he ele an ou come measu es O e all u ili y sco es (mean ± SD) Sub-g oup u ili y sco es (mean ± SD) Wallande e al. (2009) [59] Adul s ea ed o CTEV in in ancy Sel - epo ed EQ-5D ( e sion no s a ed) SF-36 VAS Ame ican Academy o O hopaedic Su geons Foo and Ankle Ques ionnai e NA O e all u ili y sco es no epo ed NA Young e al. (2010) [22] Adolescen s and young adul s wi h ce eb al palsy Sel - epo ed and p oxy (ca egi e ); p edominan ly sel - epo ed (45% p oxy) HUI3 and AQoL SRH Heal h Assessmen Ques ionnai e (HAQ) Combined age g oups HUI3: 0.30 (±0.42) AQoL: 0.28 (±0.33) U ili y sco e by age g oup (HUI3 / AQoL) ‘You h’g oup: 0.30 (±0.43) / 0.28 (±0.34) ‘Adul ’g oup: 0.31 (±0.40) / 0.28 (±0.314) You h g oup: u ili y sco e by GMFCS le el (HUI3 / AQoL) GMFCS I: 0.67 (±0.32) / 0.58 (±0.31) GMFCS II: 0.59 (±0.35) / 0.53 (±0.34) GMFCS III: 0.43 (±0.39) / 0.31 (±0.32) GMFCS IV: 0.08 (±0.25) / 0.06 (±0.12) GMFCS V: −0.13 (±0.19) / 0.01 (±0.07) Adul g oup: u ili y sco e by GMFCS le el (HUI3 / AQoL)GMFCS I: 0.64 (±0.30) / 0.52 (±0.32) GMFCS II: 0.50 (±0.39) / 0.33 (±0.24) GMFCS III: 0.53 (±0.27) / 0.39 (±0.27) GMFCS IV: 0.06 (±0.21) / 0.10 (±0.20) GMFCS V: −0.14 (±0.20) / 0.02 (±0.06) Young e al. (2013) [21] Adolescen s and young adul s wi h spina bi ida Sel - epo ed and p oxy (ca egi e ); p edominan ly sel - epo ed (15% p oxy) HUI3 and AQoL SRHHAQ Combined age g oups HUI3: 0.52 (±0.28) AQoL: 0.34 (±0.24) U ili y sco e by age g oup (HUI3 / AQoL) ‘You h’g oup: 0.58 (±0.27) / 0.37 (±0.26) ‘Adul ’g oup: 0.36 (±0.27) / 0.25 (±0.17) U ili y sco e by lesion le el (HUI3 / AQoL) Tho acic: 0.29 (±0.14) / 0.22 (± 0.14) High-lumba : 0.44 (±0.31) / 0.28 (±0.23) Low-lumba : 0.63 (±0.23) / 0.39 (± 0.21) Sac al: 0.76 (±0.20) / 0.51 (±0.33) Unknown: 0.22 (±0.02) / 0.09 (±0.04) B ay e al. Heal h Economics Re iew (2020) 10:9 Page 18 o 38 Table 6 Summa y o PBM pe o mance o included s udies S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness Ba le e al. (2010) [33] Adolescen s wi h ce eb al palsy HUI3 ision, cogni ion and pain dimensions s eadily declined as GMFCS le el inc eased, s a is ical signi icance no epo ed. Examining co ela ion coe icien s, he e was no indica ion ha he HUI3 ision ( =0.01; p= 0.92), cogni ion ( =−0.05; p= 0.59) o pain dimensions ( =0.16; p= 0.07) we e de e minan s o mo o capaci y, as measu ed using he GMFM-66. NA NA Indi iduals wi h a GMFCS le el o V exhibi ed he la ges mean dec eases in HUI3 dimension le els o e ime, anging om −0.2 (±1.2) o he HUI3 ision dimension o −0.3 (±1.3) o he HUI3 cogni ion and pain dimensions. B ay e al. (2017) [15] Child en and adolescen s wi h impai ed mobili y ( ele an condi ions: ce eb al palsy, hemiplegia, muscula dys ophy) NA NA La ge a iance be ween mean u ili y sco es de i ed om di e en PBMs, anging om 0.24 (EQ-5D-Y) o 0.53 (HUI2) o child sel - epo ed u ili y, and om 0.01 (EQ- 5D-Y) o 0.49 (HUI2) o pa en - epo ed p oxy u ili y. A signi ican esponden ype e ec was ound, wi h mean child sel - epo ed u ili y sco es signi ican ly (p≤0.021) highe han equi alen p oxies on all PBMs. Signi ican s ong co ela ions we e ound be ween u ili y sco es o child en/pa en p oxies using all measu es: EQ- 5D-Y ( =0.67; p= 0.026), HUI2 ( =0.73; p= 0.005) and HUI3 ( =0.84; p< 0.001). Using Bland-Al man plo s, su icien ag eemen be ween u ili y sco es o child en/pa en p oxies was ound o he HUI2 (CL = 0.22) and HUI3 (CL = 0.22). EQ-5D-Y exhibi ed clinically impo an disc epancies be ween child and pa en p oxy esponses (CL = 1.04). NA Bu s om e al. (2014) [11] Child en and adolescen s wi h unc ional mo o , o hopaedic and medical disabili ies ( ele an condi ions: a og yposis mul iple congeni al, myelomeningocele, ce eb al palsy, o hopaedic lowe limb de o mi ies, S a is ically signi ican (p≤0.001) di e ences be ween case and con ol g oups on all dimensions. Mean dimension sco es no epo ed, p opo ions o pa ien s choosing each dimension le el indica e case g oup S ong signi ican co ela ion was ound be ween he EQ-5D-Y anxie y/dep ession di mension and he KIDSCREEN-27 psycho logical well-being dimen sion ( =−0.51; p= 0.001); KIDSCREEN-27 physical well-being dimension NA NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 19 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness achond oplasia) epo ed mo e p oblems on all dimensions han he con ol g oup: 83% o case g oup epo ed some/a lo o p oblems on any dimension, compa ed o 37% o con ol g oup; likewise 21% o case g oup epo ed ex eme p oblems on any dimension, compa ed o 2% o con ol g oup. ( =−0.53; p= 0.001); and li e sa is ac ion ladde (LSL) ( =−0.54; p< 0.001). Mode a e co el a ion also ound be ween his dimension and he KIDSCREEN-10 HRQoL index sco e ( =−0.50; p= 0.001) and sel - epo ed heal h (SRH) (0.42; p= 0.007). The sel -ca e EQ-5D-Y di mension exhibi ed mod e a e co ela ion wi h he KIDSCREEN-27 physical wellbeing dimension ( = −0.37; p= 0.028) and he usual ac i i ies EQ-5D-Y dimension was mode a ely co ela ed wi h he KIDSCREEN-27 psychological wellbeing dimension ( =−0.35; p= 0.027). All o he co ela ions we e weak o absen . Ca azza e al. (2016) [34] Adolescen s and adul s wi h Duchenne muscula dys ophy NA NA NA NA NA Ch is ensen e al. (2016) [35] Child en and adolescen s wi h ce eb al palsy NA Using mul i a ia e linea eg ession, a signi ican associa ion was ound be ween he HUI3 pain dimension sco e a baseline and GMFCS le el (b = −0.11, β=−0.15; p< 0.036; 95% CI −0.21 o −0.01): highe pain sco e a baseline was associa ed wi h g ea e imp o emen in pain s a us in GMFCS le el I compa ed o le el V. NA NA Using one-way ANOVA analysis, a signi ican as socia ion was ound be ween physician p ima y pain ae iology and change in HUI3 pain s a us (p= 0.001): child en wi h musculoskele al pain a baseline showed sig ni ican imp o emen s (mean change 0.55; 95% CI 0.053 o 1.05) com pa ed o child en wi hou pain a baseline (mean change −0.39; 95% CI − 0.62 o −0.15) (p = 0.006). No o he associa ions we e epo ed. HUI3 pain dimension sco es did no B ay e al. Heal h Economics Re iew (2020) 10:9 Page 20 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness change signi ican ly o e ime: median sco e o 2 (ou o 5) a bo h isi s. Howe e , 55% o child en changed pain s a us o e ime: 34% wo sening, 21% imp o ing. Findlay e al. (2015) [36] Child en wi h ce eb al palsy NA NA NA NA NA Hend iksz e al. (2014) [37] Child en and adul s wi h Mo quio A synd ome A signi ican e ec o wheelchai use on u ili y ou comes was epo ed; signi ican di e ences epo ed be ween: adul non- wheelchai use s and occasional wheelchai use s (p= 0.0115); adul occasional wheelchai use s and ull- ime wheelchai use s (p= 0.0007); child occasional wheelchai use s and ull- ime wheelchai use s (p = 0.0018); and child non-wheelchai use s and ull- ime wheelchai use s (p= 0.0018). Child en who occasionally used a wheelchai had a highe mean u ili y sco e on a e age han non-wheelchai use s, al hough bo h g oups had highe a e age u ili y sco es han ull- ime wheelchai use s. NA NA NA NA Ka mu and Kulka ni (2018) [38] Child en and adolescen s wi h spina bi ida (myelomeningocele) and shun ed hyd ocephalus Using mul i a ia e eg ession analysis, ana omical le el o myelomeningocele had a signi ican e ec on u ili y sco e (p= 0.01): lowe ana omical le el o myelomeningocele NA NA NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 21 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness was associa ed wi h a highe u ili y sco e. Kennes e al. (2002) [39] Child en wi h ce eb al palsy NA Using Kendall’s au-b es o associa ion, he HUI3 dimension mos associ a ed wi h GMFCS le el was ambula ion ( au-b = 0.82; p< 0.01): highe GMFCS le el was associa ed wi h inc eased mobili y impai men . Mode a e co ela ions ( anging om au-b = 0.36 o 0.58; p< 0.01) we e ound be ween GMFCS le el and he ision, speech and dex e i y dimensions. O e all pa e ns we e simila o he ambula ion dimension, bu co ela ions we e weake . Hea ing ( au-b = 0.16; p= 0.04) and cogni ion ( au- b = 0.27; p< 0.01) dimensions had s a is ically signi ican bu low associa ion wi h GMFCS le el. The emo ion ( au-b = 0.03; p= 0.24) and pain ( au-b = 0.07; p= 0.37) dimensions we e no signi ican ly associa ed wi h GMFCS le el. NA NA NA Kulka ni e al. (2004) [40] Child en wi h hyd ocephalus NA S ong co ela ion was ound be ween u ili y sco e and he HOQ o e all heal h ( =0.81), physical heal h ( =0.88), social-emo ional ( =0.56) and cogni i e ( =0.57) sco es. NA NA NA Kulka ni e al. (2006) [41] Child en wi h hyd ocephalus NA Co ela ion be ween u ili y sco e and HOQ o e all heal h sco e was high ( =0.81), a sca e plo demons a ed NA NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 22 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness a s ong linea ela ionship. Simple and complex linea eg ession models bo h accoun ed o a la ge p opo ion o HUI2 a iabili y (adjus ed R 2 = 0.66 and 0.80 espec i ely). Kulka ni e al. (2008) [42] Child en wi h hyd ocephalus NA Mean u ili y sco e (0.58 ± 0.63) close o cHOQ mean sco es o o e all heal h (0.65 ± 0.20), Physical heal h (0.66 ± 0.25), Cogni i e heal h (0.55 ± 0.28) and Social- emo ional heal h (0.71 ± 0.19). S a is ical signi icance no epo ed. NA NA NA Kulka ni e al. (2008) [43] Child en wi h hyd ocephalus NA Signi ican co ela ion was ound be ween he cHOQ o e all heal h sco e (sel - epo ed) and u ili y sco e (p oxy- epo ed) ( =0.60; p< 0.001). NA NA NA Land eld e al. (2016) [44] Child en and adolescen s wi h Duchenne muscula dys ophy Ambula o y class was signi ican ly associa ed wi h p oxy- epo ed u ili y sco es (p< 0.001), dec easing om ea ly ambula o y class (mean 0.75) o la e non-ambula o y class (mean 0.15). Ca egi e assessmen s o heal h and men al s a us we e signi i can ly associa ed wi h u ili y sco e (p< 0.001). NA NA NA NA Lindquis e al. (2014) [45] Adul s who expe ienced hyd ocephalus in in ancy The s udy g oup had signi ican ly (p≤ 0.004) lowe dimension sco es compa ed o he con ol g oup in ision, ea ing, usual ac i i ies, men al NA NA NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 23 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness unc ion dimensions. The mos epo ed p oblems we e associa ed wi h he neu oimpai men subg oup (mean u ili y sco e 0.87 compa ed o 0.94 in he no neu oimpai men subg oup). The subg oup wi hou neu oimpai men we e no signi ican ly di e en o he con ol in e ms o mean u ili y sco e (0.94 and 0.95 espec i ely, p alue no epo ed). Li ings on and Rosenbaum (2008) [46] Adolescen s wi h ce eb al palsy NA Disa enua ed co ela ion coe icien s be ween u ili y sco es and QOL Ins umen sco es demons a ed weak o mode a e co ela ion o he being ( =0.48); belonging ( =0.35); becoming ( =0.29) and o e all quali y o li e ( =0.35) scales. The wo measu e sha ed up o 23% a iance. NA NA Gene alizabili y coe icien s we e calcula ed o assess a iabili y o sco es o e ime. Dimensions wi h g ea e s abili y (i.e. la ge G sco es) had less a iabili y be ween indi iduals o e ime. The ambula ion dimension (G = 0.94) and o e all u ili y (G = 0.91) we e ound o be highly s able; while he speech (G = 0.87), ision (G = 0.87); dex e i y (G = 0.82), cogni ion (G = 0.81), and hea ing (G = 0.72) dimensions we e mode a ely s able. The pain (G = 0.48) and emo ion (G = 0.24) dimensions we e ound o ha e low s abili y. Lopez-Bas ida e al. (2017) [47] Child en wi h spinal muscula a ophy Child en wi h Type II spinal muscula a ophy we e ound o ha e a lowe NA NA NA NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 24 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness child en wi h ce eb al palsy (mean 0.92) and child en wi h scoliosis wi h como bidi ies (mean 0.725), bu no child en wi h idiopa hic scoliosis (mean 0.889). Jus i ica ion o hese g oupings was based on sample size, hus he e is no explici explana ion as o why u ili y di e ences be ween hese g oups would be expec ed. Wallande e al. (2009) [59] Adul s ea ed o CTEV in in ancy Male pa icipan s had signi ican ly highe a e age u ili y sco e han he compa able no m g oup (p= 0.027). Male pa icipan s epo ed signi ican ly less mode a e/ex eme p oblems wi h anxie y/dep ession han he compa able no m g oup (6.3% s 21.2%; p= 0.007). Female pa icipan s had wo se u ili y on a e age han a compa able no m g oup, bu no signi ican ly. Female pa icipan s epo ed signi ican ly mo e mode a e/ex eme p oblems wi h mobili y (45% s 12.2%; p< 0.001) and usual ac i i ies (35% s 12.5%; p= 0.006) han a compa able no m g oup. NA NA NA NA Young e al. (2010) [22] Adolescen s and young adul s wi h ce eb al palsy In bo h he ‘you h’ and ‘adul ’g oups, Linea eg ession analysis e ealed ha GMFCS U ili y sco es de i ed om HUI3 we e on P oxy u ili y sco es we e gene ally lowe (by 0.16) NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 31 o 38 Table 6 Summa y o PBM pe o mance o included s udies (Con inued) S udy e e ence Condi ion(s) o in e es Known-g oup analyses Cons uc alidi y: compa ing ou comes Cons uc alidi y: compa ing PBMs Cons uc alidi y: compa ing esponden s Responsi eness u ili y sco es de e io a ed s eadily as GMFCS le el inc eased. S a is ical signi icance no epo ed le el in childhood was he mos impo an in luence on u ili y sco es; esponsible o 53.2% o a iance in HUI3 u ili y ou comes (β=−0.205; p< 0.001) and 45.2% o a iance in AQoL u ili y ou comes (β=−0.148; p< 0.001). The SRH was ound o be mode a ely co ela ed wi h u ili y sco es de i ed om he HUI3 ( =0.41; p< 0.001) and AQoL ( =0.41; p< 0.001). a e age highe han hose de i ed om AQoL ac oss all GMFCS le els; howe e s ong co ela ion was ound be ween he HUI3 and AQoL ( =0.87; p< 0.001). when adjus ed o cogni ion, gene al heal h and CP se e i y. S a is ical signi icance no epo ed. Young e al. (2013) [21] Adolescen s and young adul s wi h spina bi ida U ili y sco es de i ed om bo h HUI3 and AQoL a ied in he same way acco ding o lesion le el, wi h ho acic lesions associa ed wi h lowes u ili y. Linea eg ession analysis e ealed ha he mos impo an single ac o con ibu ing o u ili y ou comes was su gical lesion le el; esponsible o 40% o a iance in HUI3 u ili y sco es and 18% in AQoL u ili y sco es. Bo h lesion le el and age we e impo an when combined, accoun ing o 48% a iance in HUI3 u ili y sco es and 22% a iance in AQoL u ili y sco es. The SRH was ound o be mode a ely/s ongly co ela ed wi h u ili y sco es de i ed om he HUI3 ( =−0.45; p< 0.001) and AQoL ( =− 0.58; p < 0.001). The HAQ was also s ongly co ela ed wi h u ili y sco es de i ed om he HUI3 ( =0.79; p< 0.001) and AQoL ( =0.70; p< 0.001). U ili y sco es de i ed om he AQoL we e highe han om he HUI3 ac oss all lesion le el sub-g oups; how e e he AQoL and HUI3 exhibi ed s ong co el a ion ( =0.73; p< 0.001). Mean u ili y sco es we e sligh ly highe in he sel - epo ed g oup (HUI3 mean + 0.04; AQoL mean + 0.03) howe e his was based on he compa ison o you h and adul da a and he eg es sion models emained unchanged. NA B ay e al. Heal h Economics Re iew (2020) 10:9 Page 32 o 38 you h e sion (EQ-5D-Y); pa en s epo ed a lowe e- quency o p oblems on all EQ-5D-Y p oxy dimensions, pa icula ly a he s. Responsi eness Fi e s udies allowed analysis o PBM esponsi eness in CP [33,35,46,55,57]. Adolescen s wi h a GMFCS le el o V exhibi ed he la ges dec eases in HUI3 dimension le els o e ime, compa ed o adolescen s wi h GMFCS le els o III and IV [33]. Ch is ensen e al. [35] epo ed a signi ican associa ion be ween physicians’p ima y pain ae iology and change in HUI3 pain s a us (p= 0.001). Con e sely, in wo s udies u ili y ou comes did no change signi ican ly o e ime; HUI3 u ili y ou - comes we e ound o be s able o e a 1 yea pe iod o adolescen s wi h CP (G = 0.91) [46], likewise u ili y ou - comes (de i ed om HUI3 and AQoL) did no signi i- can ly change o e an 8 yea ollow-up pe iod [57]. Slaman e al. [55] u ilised he SF-6D in a andomised con olled ial, bu did no ind a signi ican di e ence be ween he con ol and in e en ion g oups a he end o he ial (p= 0.42). Spina bi ida Known-g oup analyses Th ee s udies epo ed known-g oup analyses in SB [51, 52,56], wo o which ound ha clinical ac o s had a signi ican impac on u ili y sco es. Pe ou and Kupek [51] es ima ed ha he adjus ed HUI3 disu ili y o child- hood SB om pe ec heal h was −0.55 (95% CI −0.40 o −0.70), and −0.48 (95% CI −0.33 o −0.63) om childhood no ms. A s a is ically signi ican e ec o SB diagnosis on HUI3 u ili y sco e (p< 0.001) was epo ed [52]; child en diagnosed wi h myelomeningocele (mean u ili y sco e = 0.51) ended o ha e lowe u ili y sco es compa ed o child en wi h closed dys aphism (mean u ili y sco e = 0.77). Til o d e al. [56] epo ed ha le- sion loca ion in childhood SB had a signi ican impac on o e all u ili y (p< 0.01); indi iduals wi h sac al le- sions had he highes o e all mean u ili y (0.61; ±0.26). Two s udies epo ed co ela ion be ween clinical ac- o s and u ili y sco es in SB [21,38]. Ana omical myelo- meningocele le el was ound o ha e a signi ican e ec on he HUI u ili y sco es o child en wi h myelomenin- gocele and shun ed hyd ocephalus (mean HUI sco e = 0.03; 95% CI 0.01 o 0.05; p= 0.01) [38], wi h lowe mye- lomeningocele le el showing associa ion wi h highe u ili y sco es. A simila end was epo ed by Young e al. [21], who ound ha he mos impo an single ac- o con ibu ing o u ili y ou comes in SB was su gical lesion le el, which was esponsible o be ween 18% (AQoL) and 40% (HUI3) o a iance in u ili y sco es. Con e gen alidi y: compa ing measu es Two s udies epo ed a ious le els o co ela ion be ween PBMs and o he ou come measu es in SB [21,54]. Child sel - epo ed HUI3 u ili y sco es we e no ound o be highly co ela ed wi h VAS sco es ( =0.488) [54]. Like- wise, he SRH was only mode a ely co ela ed wi h u ili y sco es in SB (HUI3: =−0.45; p<0.001 / AQoL: =− 0.58; p<0.001) [21]. Only he HAQ was ound o be s ongly co ela ed wi h u ili y sco e (HUI3: =0.79; p< 0.001 / AQoL: =0.70;p<0.001)[21]. Young e al. [21] compa ed esul s om di e en PBMs in SB, and ound ha mean u ili y sco es on he AQoL we e lowe han mean u ili y sco es on he HUI3 o all sub-g oups, despi e s ong co ela ion be ween hese measu es ( = 0.73; p< 0.001). Con e gen alidi y: compa ing esponden s Sims-Williams e al. [54] epo ed ha p oxy and sel - epo ed HUI3 u ili y sco es we e highly co ela ed o child en wi h SB ( = 0.85; signi icance no epo ed). Young e al. [21] ound ha mean sel - epo ed u ili y sco es we e sligh ly highe han equi alen p oxy sco es (HUI3 mean + 0.04; AQoL mean + 0.03) howe e e- sponden ype was no in luen ial in hei eg ession analysis. PBM esponsi eness ou comes in SB we e no ound in he li e a u e. Mixed pa ien g oups and mobili y impai men s This sec ion includes esul s om s udies which did no ocus on speci ic condi ions, and whe e sub-g oup da a could no be examined sepa a ely. Rele an condi ions/ mobili y impai men s included muscula dys ophy, spinal muscula a ophy, CP, SB, o hopaedic lowe limb de o mi ies, a og yposis mul iple congeni al, achond o- plasia and hemiplegia. Known-g oup analyses Two s udies epo ed known-g oup analyses in s udies o mixed pa ien g oups [11,51]. Pe ou and Kupek [51] ound ha child en wi h muscula dys ophy o spinal muscula a ophy had a mean u ili y sco e o 0.39, equa - ing o an adjus ed disu ili y om pe ec heal h o −0.62 (95% CI −0.471 o −0.761), and an adjus ed disu ili y om childhood no ms o −0.54 (95% CI −0.400 o − 0.690). Bu s om e al. [11] epo ed ha child en wi h a unc ional disabili y (64% congeni al; see Table 4 o pa- ien cha ac e is ics) had signi ican ly lowe EQ-5D-Y di- mension sco es han he gene al popula ion (p<0.001). Con e gen alidi y: compa ing ou comes Mode a e co ela ion was ound be ween he indi idual dimensions o he EQ-5D-Y and he dimensions o o he measu es (KIDSCREEN-27 and KIDSCREEN-10) and B ay e al. Heal h Economics Re iew (2020) 10:9 Page 33 o 38 he li e sa is ac ion ladde (LSL), when comple ed by child en wi h unc ional disabili ies [11] . The EQ-5D-Y anxie y/dep ession dimension exhibi ed signi ican co - ela ion wi h he KIDSCREEN-27 psychological well- being dimension ( =−0.51; p = 0.001), he KIDSCREEN-27 physical well-being dimension ( =− 0.53; p= 0.001), and he LSL ( =−0.54; p< 0.001) [11]. La ge a iance was obse ed be ween u ili y sco es de- i ed om di e en PBMs o young wheelchai use s; mean u ili y sco es anged om 0.24 (EQ-5D-Y) o 0.53 (HUI2) o sel - epo ing child en, and om 0.01 (EQ- 5D-Y) o 0.49 (HUI2) o pa en p oxies [15]. Con e gen alidi y: compa ing esponden s A signi ican s ong co ela ion was obse ed be ween dyads o young wheelchai use s (84.6% child en wi h CP, see Table 4 o pa ien cha ac e is ics) and pa en p oxies o a numbe o u ili y measu es: EQ-5D-Y ( = 0.67; p= 0.026), HUI2 ( = 0.73; p= 0.005) and HUI3 ( = 0.84; p< 0.001) [15]. Using Bland-Al man plo s [60], su icien ag eemen was obse ed be ween dyads o he HUI2 (CL = 0.22) and HUI3 (CL = 0.22), bu no he EQ- 5D-Y (CL = 1.04). A signi ican esponden ype e ec was ound o all measu es, wi h child sel - epo ed u il- i y sco es signi ican ly highe o he EQ-5D-Y (p= 0.012), HUI2 (p= 0.021) and HUI3 (p= 0.009) han equi alen p oxy measu es [15]. PBM esponsi eness ou comes we e no ound in he li e a u e o his pa ien g oup. Childhood hyd ocephalus (mixed ae iology) Known-g oup analyses Lindquis e al. [45] ound ha adul s wi h a his o y o hyd ocephalus (wi h o wi hou neu o-impai men ) had signi ican ly lowe 15D dimension sco es, compa ed o a con ol g oup, in he dimensions o ision (p= 0.001), ea ing (p= 0.000), usual ac i i ies (p= 0.004) and men al unc ion (p= 0.000). Con e gen alidi y: compa ing measu es Fou s udies examined he ela ionship be ween he Hyd ocephalus Ou come Ques ionnai e (HOQ) and PBMs [40–43], howe e only h ee o hese s udies pe - o med ele an s a is ical analyses [40,41,43]. Kulka ni [41] epo ed s ong co ela ion (0.81) and a s ong lin- ea ela ionship be ween HUI2 u ili y sco e and HOQ ou comes o child en wi h hyd ocephalus. Simple and complex linea eg ession models bo h accoun ed o a la ge p opo ion o HUI2 a iabili y (adjus ed R 2 = 0.66 and 0.80 espec i ely). Simila ly, a s ong co ela ion was ound be ween HUI2 u ili y sco e and he HOQ sco es o o e all heal h ( = 0.81), physical heal h ( = 0.88), social-emo ional ( = 0.56) and cogni i e ( = 0.57) [40]. Fu he mo e, a signi ican posi i e co ela ion was exhibi ed be ween sel - epo ed sco es on he child- comple ed e sion o he HOQ (cHOQ) and p oxy- epo ed u ili y sco es on he HUI3 ( = 0.60; p< 0.001) [43]. PBM esponsi eness ou comes in childhood hyd o- cephalus we e no ound in he li e a u e. O he condi ions and mobili y impai men s Only known-g oup analyses we e epo ed o he ol- lowing condi ions associa ed wi h mobili y impai men : Muscula dys ophy Land eld e al. [44] epo ed ha ambula o y s a us and age we e signi ican ly associa ed wi h HUI u ili y sco es in muscula dys ophy (HUI e sion no s a ed; p < 0.001); young ambula o s (5–7 yea s old) had he highes u ili y sco es on a e age (0.75), whils olde non- ambula o s (≥16 yea s old) had he lowes u ili y sco es on a e age (0.15). Spinal muscula a ophy Lopez-Bas ida e al. [47] epo ed ha child en wi h Type II spinal muscula a ophy ended o ha e lowe mean p oxy u ili y sco es (−0.01; ±0.35) han he combined a e age o all o ms o spinal muscula a ophy (0.16; ± 0.44), howe e s a is ical analysis was no unde aken. Mo quio A synd ome One s udy ound ha o bo h adul s and child en wi h Mo quio A synd ome, wheelchai use was signi ican ly associa ed wi h lowe u ili y sco es [37]. Signi ican di - e ences we e epo ed in he adul g oup be ween non- wheelchai use s and occasional wheelchai use s (p= 0.0115) and be ween occasional wheelchai use s and ull- ime wheelchai use s (p= 0.0007). In he child g oup signi ican di e ences we e epo ed be ween non-wheelchai use s and ull- ime wheelchai use s (p= 0.0018) and occasional wheelchai use s and ull- ime wheelchai use s (p= 0.0007). Congeni al club oo Wallande e al. [59] ound ha male adul pa ien s wi h congeni al club oo (CCF) had signi ican ly be e o e all u ili y sco es han he male no m g oup (p = 0.027). The emale CCF g oup had a lowe a e age u ili y sco e han he no m g oup, bu no signi ican ly (signi icance le el no epo ed). Mic ocephaly Pe ou and Kupek [51] ound ha child en wi h mic o- cephaly had a mean u ili y sco e o 0.14, equa ing o an adjus ed disu ili y om pe ec heal h o −0.82 (95% CI −0.67 o −0.97), and an adjus ed disu ili y om child- hood no ms o −0.75 (95% CI −0.60 o −0.90). B ay e al. Heal h Economics Re iew (2020) 10:9 Page 34 o 38 Discussion The esul s om his sys ema ic e iew demons a e ha PBMs ha e been used in a ela i ely small numbe o s udies ela ing o congeni al mobili y impai men s. In condi ions such as CP and SB, inc eased clinical se e i y appea s o be associa ed wi h dec eased u ili y. This is pa icula ly e iden using he HUI3, which was also he mos commonly used PBM ound in his e iew. In pa - icula , he e appea s o be a ela ionship be ween u ili y ou comes and GMFCS le el in CP, and clinical ac o s such as lesion le el in SB. In case-con ol s udies, u ili y ou comes ended o be signi ican ly lowe in he case g oups, al hough i is wo h no ing ha in one s udy he male case-g oup had signi ican ly highe u ili y ou - comes compa ed o he con ol [59]. In o de o demons a e su icien applicabili y and sensi i i y in a speci ic disease o disabili y, associa ion be ween PBMs and alida ed clinical/condi ion-speci ic ou comes is o key impo ance. In his espec exis ing PBMs show weakness in a ious condi ions associa ed wi h congeni al mobili y impai men s; exhibi ing gene - ally limi ed co ela ion wi h measu es such as he QOL Ins umen , VAS, SRH, KIDSCREEN-27, KIDSCREEN- 10 and LSL. Only he GMFCS and HOQ/cHOQ ap- pea ed o be well co ela ed wi h PBMs ac oss a numbe o s udies, al hough i is impo an o no e ha GMFCS is a classi ica ion sys em o g oss mo o unc ion and no an ou come measu e. The esul s om his sys ema ic e iew highligh im- po an conside a ions o he use o PBMs in heal h s a es associa ed wi h congeni al mobili y impai men . I is i s o no e ha he use o PBMs has been domina ed by s udies in CP, ollowed by SB. This is somewha un- su p ising gi en ha hese a e wo o he mos p e alen congeni al disabili ies which a ec mobili y. Secondly, i is impo an o acknowledge ha only wo s udies o- cussed on adul s alone, and ha bo h o hese s udies we e measu ing u ili y ou comes in adul s ollowing con- di ions expe ienced in childhood [45,59]. This ocus on child en and adolescen s is again unsu p ising, as many congeni al condi ions can be li e-limi ing, hus examin- ing heal h ou comes a a young age becomes pa icula ly impo an . Howe e , his also shows a lack o ocus on he heal h ou comes o adul s who ha e li e-long expe i- ence o mobili y impai men , and he po en ial ways in which hei heal h ou comes could change o e ime o be imp o ed. The e is some e idence o demons a e ha di e en PBMs a y in hei es ima ion o u ili y ou comes in s a es o impai ed mobili y. Fo ins ance, B ay e al. [15] ound la ge a ia ion be ween he EQ-5D-Y and HUI2/3 u ili y sco es o wheelchai use s. Likewise, Usuba e al. [57] and Young e al. [21,22] ound ha u ili y ou - comes we e gene ally highe when de i ed om he AQoL han he HUI3 o indi iduals wi h CP, bu ice e sa o indi iduals wi h SB. This is despi e he s ong co ela ion be ween he AQoL and HUI3 in hese popu- la ions [21,22]. Un o una ely, s a is ical di e ences be- ween hese measu es we e no epo ed, bu i is s ill impo an o conside he implica ions ha hese di e - ences could ha e on subsequen QALY ou comes. Fo ins ance, i one PBM we e o p oduce signi ican ly highe u ili y sco es han ano he , his would mean sig- ni ican ly di e en es ima es o cos pe QALYs and hus es ima es o cos -e ec i eness. A p esen he e is lim- i ed e idence o enable heal h economis s and e- sea che s o choose be ween hese di e en PBMs o use in congeni al mobili y impai men s. Despi e documen ed limi a ions [61], QALYs ha e be- come inc easingly in luen ial in heal h policy as a means o de e mine he cos -e ec i eness o new ea men s and se ices, and he e o e guide heal hca e unding and p i- o i isa ion decisions. I is he e o e impe a i e ha he PBMs used o de elop QALYs a e accu a e. O he wise, he cos -e ec i eness o ce ain in e en ions in ce ain pa ien g oups could be unde es ima ed. This in u n could impac unding and p io i isa ion decisions. In he con ex o congeni al mobili y impai men , his could im- pac he p o ision o AMT and o he mobili y-enhancing in e en ions, and subsequen ly impac pa ien ou comes. This is pa icula ly impo an conside ing he ongoing is- sues o unme need in assis i e echnology p o ision. The WHO P io i y Assis i e P oduc s Lis (APL) was launched in 2016 o help ackle unme need [62]. The APL con ains 50 p io i y assis i e echnology p oduc s, and was p o- duced h ough consul a ion wi h use s, expe s and o he key s akeholde s. App op ia e PBM da a, and subsequen es ima es o cos -e ec i eness, could help o in o m he APL and ensu e ha he mos e ec i e and cos -e ec i e AMTs a e p io i ised. Conside ing ha he majo i y o e idence ound in his e iew ela ed o child en, he ela ionship be ween sel - epo ed and p oxy u ili y ou comes is pa icula ly sig- ni ican . The esul s om a ious s udies in his e iew demons a e ha p oxy- epo ing o u ili y is consis - en ly di e en o ha o sel - epo e s, including signi i- can esponden - ype e ec s and limi ed ag eemen be ween esponden s. In e es ingly, p oxy esponden s we e ound o bo h unde es ima e and o e es ima e u il- i y ou comes compa ed o sel - epo e s. I is he e o e impo an o p io i ise ou come measu emen om he pa ien , al hough his can be challenging in popula ions who may lack capaci y, such as young child en and indi- iduals wi h cogni i e impai men s. Me hodological implica ions Due o he unde lying ade-o be ween quan i y and quali y o li e in he calcula ion o u ili y alues and B ay e al. Heal h Economics Re iew (2020) 10:9 Page 35 o 38 subsequen QALYs, he e is a endency o lowe alue o be placed on ex ending he leng h o li e o people wi h long- e m disabili ies [10,63], as hei quali y o li e is ou inely conside ed o be wo se han ha o an able- bodied pe son. Thus, when using he QALY amewo k o assess he ou comes o indi iduals wi h disabili ies, i is di icul o achie e subs an ially highe quali y o li e when compa ed o indi iduals wi hou disabili ies, ais- ing conce ns abou bias [10]. To some ex en hese is- sues could be a esul o using gene ic PBMs o alue disabled heal h s a es. One o he unde lying issues o using PBMs in disabil- i y is ha he de ini ion o HRQoL di e s p o oundly be- ween people wi h disabili ies and he gene al public [64]. When asked o de ine HRQoL, young wheelchai use s ocus on a numbe o concep s no explici ly mea- su ed using gene ic PBMs, such as abili y o adap , achie emen and independence [17]. The expe ience o disabili y also a ec s HRQoL pe cep ions. Mechanisms o adap a ion, coping and adjus men can help indi id- uals wi h disabili ies o expe ience diminishing e ec s o hei HRQoL o e ime. These p ocesses a e also in lu- enced by he onse o disabili y, as indi iduals wi h con- geni al disabili ies demons a e be e adap a ion han indi iduals wi h acqui ed disabili ies [2]. The e alua ion o s a es o disabili y by non-disabled indi iduals may he e o e cause such s a es o ha e an exagge a ed pe - cei ed impac on HRQoL and heal h s a us [65], pa icu- la ly wi h ega ds o congeni al disabili y. When assessing he desi abili y o hypo he ical heal h s a es, indi iduals ocus on he ansi ion om hei own heal h s a e o he hypo he ical heal h s a e, hus gene al public belie s abou he impac o disabili y do no al- ways e lec he li ed expe ience [66,67]. Focus on pe - sonal ansi ion means ha p ocesses such as adap a ion a e no accoun ed o , causing a disc epancy in how s a es o disabili y impac HRQoL [9]. An al e na i e app oach is o use mo e sensi i e condi ion-speci ic measu es o model u ili y alues on gene ic PBMs. Al hough his app oach is ad oca ed by NICE [68] he e a e se ious conce ns abou he alidi y o modelled u ili y alues [69], as i canno be assumed ha modelled u ili y alues a e ep esen a i e o di ec ly measu ed u ili y alues [70]. Using modelled u ili y da a o guide unding and esou ce alloca ion decisions is he e o e con o e sial. Fo ins ance, Sido a e al. [71] mapped he 12-I em Mul iple Scle osis Walking Scale (MSWS-12) on o he EQ-5D-3 L. While p edic ion es i- ma es we e ela i ely p ecise o pa ien s wi h mode - a ely impai ed mobili y, hey we e signi ican ly less accu a e o indi iduals wi h se e e impai men s. Neilson e al. [72] sugges supplemen ing PBMs wi h addi ional ques ions ela ing o unc ional ac i i ies which ha e a la ge impac on o e all quali y o li e, such as ‘si ing’ o AMT use s. Fo ins ance, Pe sson e al. [73] added complimen a y mobili y and social ela ion- ship i ems o he EQ-5D-3 L o inc ease sensi i i y in disabled popula ions. Howe e , his app oach assumes ha supplemen al ques ions can be mapped on o he heal h s a e p e e ence alues o exis ing measu es wi h- ou impac ing accu acy. Limi a ions and challenges De ining he e m congeni al mobili y impai men was one o he key challenges o designing his sys ema ic e- iew. An NHS pos u e and mobili y se ice manage was consul ed o help cons uc he sea ch e ms, and a numbe o p elimina y sea ches we e ca ied ou o es sea ch e ms o bo h sensi i i y and scope. A mul i ude o condi ions and disabili ies can a ec mobili y om bi h o ea ly in ancy, hus we a emp ed o co e a wide a ie y o hese in ou sea ch e ms, bu accep ha he e a e likely o be condi ions and disabili ies which we e missed. Gi en he sea ch esul s, we a e con iden ha we ha e cap u ed he as majo i y o ele an s ud- ies ela ing o a leas he mos common o ms o con- geni al mobili y impai men . One key issue was conside ing whe he o include s udies ela ing o hyd o- cephalus in his e iew. Al hough hyd ocephalus is no always associa ed wi h mobili y impai men , i can cause mo emen issues and is commonly ela ed o ele an condi ions such as CP and SB. We he e o e chose o in- clude s udies ela ed o childhood hyd ocephalus. We chose speci ically o ocus on congeni al mobili y impai men due o he signi ican di e ences in li e sa - is ac ion, sel -iden i y and sel -e icacy expe ienced by people wi h congeni al disabili ies compa ed o people wi h acqui ed disabili ies [2]. Fu he esea ch could compa e PBM pe o mance in congeni al and acqui ed mobili y impai men s. P e ious e iews ha e epo ed mixed esul s ega ding he alidi y and esponsi eness o exis ing PBMs in he assessmen o heal h s a es asso- cia ed wi h acqui ed mobili y impai men s, such as heuma oid a h i is [24] and mul iple scle osis [26]. Conclusion To ou knowledge, his is he i s sys ema ic e iew o he use o PBMs in congeni al mobili y impai men . E i- dence sugges s ha exis ing gene ic PBMs exhibi im- po an issues ela ing o alidi y and esponsi eness, and hus ca e mus be aken when selec ing a PBM as an ou come measu e in his con ex . Condi ion o dis- abili y speci ic app oaches o u ili y measu emen , such as he mobili y and quali y o li e (MobQoL) ou come measu e [74], could imp o e he sensi i i y and applic- abili y o u ili y measu emen in his con ex . B ay e al. Heal h Economics Re iew (2020) 10:9 Page 36 o 38 Abb e ia ions AMT: Assis i e mobili y echnologies; APL: WHO P io i y Assis i e P oduc s Lis ; APPT: Adolescen Pedia ic Pain Tool; AQoL: Assessmen o Quali y o Li e; BPI-SF: B ie Pain In en o y Sho Fo m; CCF: Congeni al club oo ; cHOQ: Child-comple ed e sion o he Hyd ocephalus Ou come Ques ionnai e; CI: Con idence in e al; CP: Ce eb al palsy; CRD: Cen e o Re iews and Dissemina ion; CTEV: Congeni al alipes equinus a us; DARE: Da abase o Abs ac s o Re iews o E ec s; DCGM-37: DISABKIDS Ch onic Gene ic Module; DSM: DISABKIDS Smiley Measu e; EQ-5D: Eu oQoL Fi e-Dimension; EQ-5D-Y: Eu oQoL Fi e-Dimension - You h e sion; EQ-5D-3 L: Eu oQoL Fi e-Dimension - Th ee Le el e sion; EQ-5D-5 L: Eu oQoL Fi e- Dimension - Fi e Le el e sion; GMFCS: G oss Mo o Func ion Classi ica ion Sys em; GMFM-66: G oss Mo o Func ion Measu e 66 I ems; HAQ: Heal h Assessmen Ques ionnai e; HOQ: Hyd ocephalus Ou come Ques ionnai e; HUI: Heal h U ili ies Index; HRQoL: Heal h- ela ed quali y o li e; HTA: Heal h Technology Assessmen ; LSL: Li e Sa is ac ion Ladde ; MeSH: Medical Subjec Headings; MSWS-12: 12-I em Mul iple Scle osis Walking Scale; NHS: Na ional Heal h Se ice; NHS EED: NHS Economic E alua ion Da abase; NICE: Na ional Ins i u e o Heal h and Ca e Excellence; PBM: P e e ence-based measu e; PedsQL: Pedia ic Quali y o Li e In en o y; QALY: Quali y-adjus ed li e yea ; QOL Ins umen : Quali y o Li e Ins umen o People wi h De elopmen al Disabili ies; QWB: Quali y o Well-Being scale; RR: Rela i e isk; SAROMM: Spinal Alignmen and Range o Mo ion Measu e; SB: Spina bi ida; SD: S anda d de ia ion; SDQ: S eng h and Di icul ies Ques ionnai e; SF- 36: 36-I em Sho Fo m Heal h Su ey; SF-6D: Sho -Fo m Six-Dimension; SRH: Sel - epo ed heal h; UN: Uni ed Na ions; VAS: Visual analogue scale; WeeFIM: Func ional Independence Measu e o Child en; WHO: Wo ld Heal h O ganiza ion; WRAT: Wide Range Achie emen Tes Acknowledgemen s The au ho ’s would like o acknowledge he suppo o D . Ha e h Al-Janabi, P o esso Joanna Coas , P o esso Debo ah Fi szimmons, Ms. K ys Ja is and P o esso Ka he ine Payne o ac ing as ad iso s o he p ojec . Au ho s’con ibu ions All au ho s we e esponsible o designing he sys ema ic e iew, de eloping he o iginal e iew p o ocol and edi ing he manusc ip . NB de ised he sys ema ic e iew, p epa ed he manusc ip and syn hesised ex ac ed da a. LHS conduc ed he e iew sea ches and led he s udy app aisal p ocess. NB and LHS sc eened pape s o eligibili y and quali y, and ex ac ed e idence wi h suppo om RTE. All au ho (s) ead and app o ed he inal manusc ip . Funding This sys ema ic e iew was unded by he Welsh Go e nmen h ough Heal h and Ca e Resea ch Wales. The unding body had no ole in he design, conduc o epo ing o his sys ema ic e iew. A ailabili y o da a and ma e ials As his is a sys ema ic e iew, he e was no p ima y da a gene a ed as pa o his esea ch. All o he da a u ilised in his e iew is a ailable om he ci ed li e a u e, and has been summa ised in Tables 4,5and 6. E hics app o al and consen o pa icipa e No applicable, his is a sys ema ic e iew. Consen o publica ion No applicable, his is a sys ema ic e iew. Compe ing in e es s The au ho s decla e ha hey ha e no compe ing in e es s. Recei ed: 4 Decembe 2019 Accep ed: 8 Ap il 2020 Re e ences 1. Depa men o Wo k and Pensions. Family Resou ces Su ey 2016/2017. London: Depa men o Wo k and Pensions; 2018. 2. Boga KR. The ole o disabili y sel -concep in adap a ion o congeni al o acqui ed disabili y. Rehabil Psychol. 2014;59(1):107–15. 3. Medicines and Heal hca e P oduc s Regula o y Agency. Assis i e echnology: de ini ion and sa e use. London: Depa men o Heal h; 2017. 4. Tebbu E, B odmann R, Bo g J, e al. Assis i e p oduc s and he sus ainable de elopmen goals (SDGs). Glob Heal h. 2016;12(1):79. 5. UN Gene al Assembly. Con en ion on he igh s o pe sons wi h disabili ies. 2006. A ailable a : h ps://www.un.o g/de elopmen /desa/disabili ies/ con en ion-on- he- igh s-o -pe sons-wi h-disabili ies.h ml [Accessed 30 Ma ch 2020]. 6. Wo ld Heal h O ganiza ion. Imp o ing access o assis i e echnology: epo by he sec e a ia . Gene a: WHO; 2016. 7. NHS Imp o ing Quali y. Righ chai , igh ime, igh now. London: NHS Imp o ing Quali y; 2014. 8. Ogden J. QALYs and hei ole in he NICE decision-making p ocess. P esc ibe . 2017;28(4):41–3. 9. Ve s eegh MM, B ouwe WB. Pa ien and gene al public p e e ences o heal h s a es: a call o econside cu en guidelines. Soc Sci Med. 2016;16: 16–74. 10. Pe i DA, Raza S, Naugh on B, Roscoe A, Ramak ishnan A, e al. The limi a ions o QALY: a li e a u e e iew. J S em Cell Res The . 2016;6:334. 11. Bu s öm K, Ba onek BEW, Sun S, Egma AC. EQ-5D-Y as a heal h- ela ed quali y o li e measu e in child en and adolescen s wi h unc ional disabili y in Sweden: es ing easibili y and alidi y. Ac a Paedia . 2014; 103(4):426–35. 12. Hagbe g L, He mansson L, F ed iksson C, Pe e sson I. Cos -e ec i eness o powe ed mobili y de ices o elde ly people wi h disabili y. Disabil Rehabil Assis Technol. 2015;30:1–6. 13. Mo is C, Janssens A, Alla d A, Coon JT, Shilling V, Tomlinson R, e al. In o ming he NHS Ou comes F amewo k: e alua ing meaning ul heal h ou comes o child en wi h neu odisabili y using mul iple me hods including sys ema ic e iew, quali a i e esea ch, Delphi su ey and consensus mee ing. Heal Se Deli Res. 2014;2:15. 14. Pe sson J, Husbe g M. Can we ely on QALYs o assis i e echnologies? Technol Disabil. 2012;24(1):93–100. 15. B ay N, Noyes J, Ha is N, Edwa ds RT. Measu ing he heal h- ela ed quali y o li e o child en wi h impai ed mobili y: examining co ela ion and ag eemen be ween child en and pa en p oxies. BMC Res No es. 2017; 10(1):1–8. 16. Ba onek A, Sa as e H, Danielsson D. Heal h- ela ed quali y o li e and ambula ion in child en wi h myelomeningocele in a Swedish popula ion. Ac a Paedia . 2012;101:953–6. 17. B ay N, Noyes J, Ha is N, Edwa ds R. De ining heal h- ela ed quali y o li e o young wheelchai use s: a quali a i e heal h economics s udy. PLoS One. 2017;12(6):1–20. 18. Sco DL, Khoshaba B, Choy EH, Kingsley GH. Limi ed co ela ion be ween he heal h assessmen ques ionnai e (HAQ) and Eu oQol in heuma oid a h i is: ques ionable alidi y o de i ing quali y adjus ed li e yea s om HAQ. Ann Rheum Dis. 2007;66(11):1534–7. 19. Wol e F, Hawley DJ. Measu emen o he quali y o li e in heuma ic diso de s using he Eu oqol. B J Rheuma ol. 1997;36:786–93. 20. Hulme C, Long AF, Knea sey R, Reid G. Using he EQ-5D o assess heal h- ela ed quali y o li e in olde people. Age Ageing. 2004;33(5):504–7. 21. Young NL, She idan K, Bu ke TA, Mukhe jee S, McCo mick A. Heal h ou comes among you hs and adul s wi h Spina bi ida. J Pedia . 2013; 162(5):993–8. 22. Young N, Rochon T, McCo mick A, Law M, Wedge J, Fehlings D. The heal h and quali y o li e ou comes among you h and Young adul s wi h ce eb al palsy. A ch Phys Med Rehabil. 2010;91(1):143–8. 23. And esen EM, Fou s BS, Romeis JC, B ownson CA. Pe o mance o heal h- ela ed quali y-o -li e ins umen s in a spinal co d inju ed popula ion. A ch Phys Med Rehabil. 1999;80(8):877–84. 24. Ha ison MJ, Da ies LM, Bansback NJ, Ing am M, Anis AH, Symmons DP. The alidi y and esponsi eness o gene ic u ili y measu es in heuma oid a h i is: a e iew. J Rheuma ol. 2008;35(4):592. 25. Mpundu-Kaambwa C, Chen G, Huynh E, Russo R, Ra cli e J. A e iew o p e e ence-based measu es o he assessmen o quali y o li e in child en and adolescen s wi h ce eb al palsy. Qual Li e Res. 2018;27:1781. 26. Kuspina A, Mayo N. A e iew o he psychome ic p ope ies o gene ic u ili y measu es in mul iple scle osis. Pha macoeconomics. 2014;32:759–73. 27. Cen e o Re iews and Dissemina ion. Sys ema ic Re iews: CRD’s Guidance o Unde aking Re iews in Heal h Ca e. Yo k: Uni e si y o Yo k; 2009. 28. Tosh J, B azie J, E ans P, Longwo h L. A e iew o gene ic p e e ence- based measu es o heal h- ela ed quali y o li e in isual diso de s. Value Heal h. 2012;15(1):118–27. B ay e al. Heal h Economics Re iew (2020) 10:9 Page 37 o 38 29. Papaioannou D, B azie J, Pa y G. How alid and esponsi e a e gene ic heal h s a us measu es, such as EQ-5D and SF-36, in schizoph enia? A sys ema ic e iew. Value Heal h. 2011;14(6):907–20. 30. Fi zsimmons D, Gilbe J, Howse F, Young T, A a as JI, B éda A, e al. A sys ema ic e iew o he use and alida ion o heal h- ela ed quali y o li e ins umen s in olde cance pa ien s. Eu J Cance . 2009;45(1):19–32. 31. Mokkink LB, Te wee CB, Pa ick DL, Alonso J, S a o d PW, Knol DL, e al. The COSMIN s udy eached in e na ional consensus on axonomy, e minology, and de ini ions o measu emen p ope ies o heal h- ela ed pa ien - epo ed ou comes. J Clin Epidemiol. 2010;63(7):737–45. 32. Junipe EF, Guya GH, Jaeshke R. How o de elop and alida e a new heal h- ela ed quali y o li e ins umen . In: quali y o li e and Pha macoeconomics in clinical ials. Philadelphia: Lippinco -Ra en Publishe s; 1996. 33. Ba le DJ, Hanna SE, A e y L, S e enson RD, Galuppi B. Co ela es o decline in g oss mo o capaci y in adolescen s wi h ce eb al palsy in g oss mo o unc ion classi ica ion sys em le els III o V: an explo a o y s udy. De Med Child Neu ol. 2010;52(7):155–60. 34. Ca azza M, Kod a Y, A meni P, De San is M, López-Bas ida J, Line o á R, e al. Social/economic cos s and heal h- ela ed quali y o li e in pa ien s wi h Duchenne muscula dys ophy in Eu ope. Eu J Heal h Econ. 2016; 17(S1):19–29. 35. Ch is ensen R, MacIn osh A, Swi ze L, Fehlings D. Change in pain s a us in child en wi h ce eb al palsy. De Med Child Neu ol. 2017;59(4):374–9. 36. Findlay B, Swi ze L, Na ayanan U, Chen S, Fehlings D. In es iga ing he impac o pain, age, g oss mo o unc ion classi ica ion sys em, and sex on heal h- ela ed quali y o li e in child en wi h ce eb al palsy. De Med Child Neu ol. 2016;58(3):292–7. 37. Hend iksz CJ, La e y C, Coke M, Uca S, Jain M, Bell L, e al. Bu den o disease in pa ien s wi h Mo quio a synd ome: esul s om an in e na ional pa ien - epo ed ou comes su ey. O phane J Ra e Dis. 2014;9(1):32. 38. Ka mu BS, Kulka ni AV. Medical and socioeconomic p edic o s o quali y o li e in myelomeningocele pa ien s wi h shun ed hyd ocephalus. Childs Ne Sys . 2018;34(4):741–7. 39. Kennes J, Raina P, Ca e H. Heal h s a us o wi h ce eb al palsy : in o ma ion om a popula ion-based sample. De Med Child Neu ol. 2002;44(2):240–7. 40. Kulka ni AV, Rabin D, D ake JM. An ins umen o measu e he heal h s a us in child en wi h hyd ocephalus: he hyd ocephalus ou come ques ionnai e. J Neu osu g Pedia . 2004;101(2):134–40. 41. Kulka ni AV. Dis ibu ion-based and ancho -based app oaches p o ided di e en in e p e abili y es ima es o he hyd ocephalus ou come ques ionnai e. J Clin Epidemiol. 2006;59(2):176–84. 42. Kulka ni AV, Coch ane DD, McNeely PD, Shams I. Medical, social, and economic ac o s associa ed wi h heal h- ela ed quali y o li e in Canadian child en wi h hyd ocephalus. J Pedia . 2008;153(5):689–95. 43. Kulka ni AV, Coch ane DD, Mcneely PD, Shams I. Compa ing child en’s and pa en s’pe spec i es o heal h ou come in paedia ic hyd ocephalus. De Med Child Neu ol. 2008;50(8):587–92. 44. Land eld E, Lindg en P, Bell CF, Guglie i M, S aub V, Lochmülle H, e al. Heal h- ela ed quali y o li e in pa ien s wi h Duchenne muscula dys ophy: a mul ina ional, c oss-sec ional s udy. De Med Child Neu ol. 2016;58(5): 508–15. 45. Lindquis B, Fe nell E, Pe sson E-K, U eb an P. Quali y o li e in adul s ea ed in in ancy o hyd ocephalus. Childs Ne Sys . 2014;30(8):1413–8. 46. Li ings on MH, Rosenbaum PL. Adolescen s wi h ce eb al palsy: s abili y in measu emen o quali y o li e and heal h- ela ed quali y o li e o e 1 yea . De Med Child Neu ol. 2008;50(9):696–701. 47. López-Bas ida J, Peña-Longoba do LM, A anda-Reneo I, Tizzano E, Se on M, Oli a-Mo eno J. Social/economic cos s and heal h- ela ed quali y o li e in pa ien s wi h spinal muscula a ophy (SMA) in Spain. O phane J Ra e Dis. 2017;12(1):1–7. 48. Mo ow AM, Hayen A, Quine S, Scheinbe g A, C aig JC. A compa ison o doc o s’, pa en s’and child en’s epo s o heal h s a es and heal h- ela ed quali y o li e in child en wi h ch onic condi ions. Child Ca e Heal h De . 2012;38(2):186–95. 49. Penne M, Xie WY, Binepal N, Swi ze L, Fehlings D. Cha ac e is ics o pain in child en and you h wi h ce eb al palsy. Pedia ics. 2013;132(2):e407–13. 50. Pe ez-Sousa MA, Sanchez-Toledo O, Fue e NG. Pa en -child disc epancy in he assessmen o heal h- ela ed quali y o li e using he EQ-5D-Y ques ionnai e. A ch A gen Pedia . 2017;115:6. 51. Pe ou S, Kupek E. Es ima ing p e e ence-based heal h u ili ies index ma k 3 u ili y sco es o childhood condi ions in England and Sco land. Med Decis Mak. 2009;29(3):291–303. 52. Rocque BG, Bishop ER, Scogin MA, Hopson BD, A ynchyna AA, Boddi o d CJ, e al. Assessing heal h- ela ed quali y o li e in child en wi h spina bi ida. J Neu osu g Pedia . 2015;15:144–9. 53. Rosenbaum PL, Li ings on MH, Palisano RJ, Galuppi BE, Russell DJ. Quali y o li e and heal h- ela ed quali y o li e o adolescen s wi h ce eb al palsy. De Med Child Neu ol. 2007;49(7):516–21. 54. Sims-Williams HJ, Sims-Williams HP, Mbabazi Kabachelo E, Wa BC. Quali y o li e among child en wi h spina bi ida in Uganda. A ch Dis Child. 2017; 102(11):1057–61. 55. Slaman J, Van Den Be g-Emons R, Tan SS, Russchen H, Van Mee e en J, S am H, e al. Cos -u ili y o a li es yle in e en ion in adolescen s and young adul s wi h spas ic ce eb al palsy. J Rehabil Med. 2015;47(4):338–45. 56. Til o d JM, G osse SD, Robbins JM, Pyne JM, Cle es MA, Hobbs CA. Heal h s a e p e e ence sco es o child en wi h spina bi ida and hei ca egi e s. Qual Li e Res. 2005;14(4):1087–98. 57. Usuba K, Oddson B, Gau hie A, Young NL. Changes in g oss mo o unc ion and heal h- ela ed quali y o li e in adul s wi h ce eb al palsy: an 8-yea ollow-up s udy. A ch Phys Med Rehabil. 2014;95(11):2071–7. 58. Vi ale MG, Le y DE, Johnson MG, Gelijns AC, Moskowi z AJ, Roye BP, e al. Assessmen o quali y o li e in adolescen pa ien s wi h o hopaedic p oblems: a e adul measu es app op ia e? J Pedia O hop. 2001;21(5):622–8. 59. Wallande H, La sson S, Bjönness T, Hansson G. Pa ien - epo ed ou come a 62 o 67 yea s o age in 83 pa ien s ea ed o congeni al club oo . J Bone Join Su g (B ). 2009;91–B(10):1316–21. 60. Bland MJ, Al man D. S a is ical me hods o assessing ag eemen be ween wo me hods o clinical measu emen . Lance . 1986;327(8476):307–10. 61. Whi ehead SJ, Ali S. Heal h ou comes in economic e alua ion: he QALY and u ili ies. B Med Bull. 2010;96(1):5–21. 62. Wo ld Heal h O ganiza ion. P io i y assis i e p oduc s lis . Gene a: WHO; 2016. 63. Singe P, McKie J, Kuhse H, Richa dson J. Double jeopa dy and he use o QALYs in heal h ca e alloca ion. J Med E hics. 1995;21(3):144–50. 64. And esen EM, Meye s AR. Heal h- ela ed quali y o li e ou comes measu es. A ch Phys Med Rehabil. 2000;81(12 SUPPL. 2):30–45. 65. Edeje T, Tessa R, Bla ussen R, Adam T, Hu ubessy R, Acha ya A, e al. Me hods o gene alized cos - e ec i eness analysis, in making choices in heal h: WHO guide o cos -e ec i eness analysis. Gene a: Wo ld Heal h O ganiza ion; 2004. 66. Dolan P, Kahneman D. In e p e a ions o u ili y and hei implica ions o he alua ion o heal h. Econ J. 2008;118:215–34. 67. Ubel PA, Loewens ein G, Jepson C. Whose quali y o li e? A commen a y explo ing disc epancies be ween heal h s a e e alua ions o pa ien s and he gene al public. Qual Li e Res. 2003;12(6):599–607. 68. Na ional Ins i u e o Heal h and Clinical Excellence. Guide o he me hods o echnology app aisal. London; 2013. 69. Round J, Haw on A. S a is ical alchemy: concep ual alidi y and mapping o gene a e heal h s a e u ili y alues. Pha macoeconomics. 2017;1(4):1–7. 70. McCabe C, Edlin R, Meads D, B own C, Kha oubi S. Cons uc ing indi ec u ili y models: some obse a ions on he p inciples and p ac ice o mapping o ob ain heal h s a e u ili ies. Pha macoeconomics. 2013;31(8):635–41. 71. Sido a MF, Limone BL, Coleman CI. Mapping o mul iple scle osis walking scale (MSWS-12) o i e-dimension Eu oQol (EQ-5D) heal h ou comes: an independen alida ion in a andomized con ol coho . Pa ien Rela Ou come Meas. 2016;3(7):13–8. 72. Neilson A, Hogg J, Malek M, Rowley D. Impac o su gical and o ho ic in e en ion on he quali y o li e o people wi h p o ound in ellec ual and mul iple disabili ies and hei ca e s. J Appl Res In ellec Disabil. 2000;13: 216–38. 73. Pe sson J, And ich R, Van Beekum T, B odin H, Lo en sen O, Wessels R, e al. P e e ence based assessmen o he quali y o li e o disabled pe sons. Technol Disabil. 2002;14(3):119–24. 74. B ay N, Spence LH, Tue sley L, Edwa ds RT. De elopmen o he MobQoL pa ien epo ed ou come measu e o mobili y- ela ed quali y o li e. Disabili y and Rehabili a ion. 2020; h ps://doi.o g/10.1080/09638288.2020. 1741701. Publishe ’sNo e Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in published maps and ins i u ional a ilia ions. B ay e al. Heal h Economics Re iew (2020) 10:9 Page 38 o 38