Effectiveness of a Transdiagnostic Guided Internet-Delivered Protocol for Emotional Disorders Versus Treatment as Usual in Specialized Care: Randomized Controlled Trial

O iginal Pape E ec i eness o a T ansdiagnos ic Guided In e ne -Deli e ed P o ocol o Emo ional Diso de s Ve sus T ea men as Usual in Specialized Ca e: Randomized Con olled T ial Albe o González-Robles1, PhD; Amanda Díaz-Ga cía1, PhD; Azucena Ga cía-Palacios1,2, PhD; Pablo Roca3, MSc; Josep An oni Ramos-Qui oga4,5,6,7, PhD; C is ina Bo ella1,2, PhD 1Depa men o Basic and Clinical Psychology, and Psychobiology, Uni e si a Jaume I, Cas ellón de la Plana, Spain 2CIBER Fisiopa ología Obesidad y Nu ición (CIBERObn), Ins i u o Ca los III, Mad id, Spain 3Depa men o Pe sonali y, Assessmen , and Clinical Psychology, Uni e sidad Complu ense de Mad id, Mad id, Spain 4Depa men o Psychia y, Hospi al Uni e si a i Vall d'Heb on, Ba celona, Spain 5G oup o Psychia y, Men al Heal h and Addic ions, Vall d'Heb on Resea ch Ins i u e (VHIR), Ba celona, Spain 6Biomedical Ne wo k Resea ch Cen e on Men al Heal h (CIBERSAM), Ba celona, Spain 7Depa men o Psychia y and Fo ensic Medicine, Uni e si a Au ònoma de Ba celona, Ba celona, Spain Co esponding Au ho : Albe o González-Robles, PhD Depa men o Basic and Clinical Psychology, and Psychobiology Uni e si a Jaume I Sos Bayna A enue, Campus del Riu Sec Resea ch II Building, Labpsi ec Cas ellón de la Plana, 12071 Spain Phone: 34 964387646 ex 7646 Email: [email p o ec ed] Abs ac Backg ound: Anxie y diso de s and dep ession (emo ional diso de s) a e highly p e alen men al diso de s. Ex ensi e empi ical e idence suppo s he e icacy o cogni i e beha io al he apy (CBT) o he ea men o hese diso de s. Howe e , he e a e s ill some ba ie s ela ed o hei dissemina ion and implemen a ion, which make i di icul o pa ien s o ecei e hese ea men s, especially in public heal h ca e se ings whe e esou ces a e limi ed. Recen ad ances in imp o ing CBT dissemina ion encompass di e en pe spec i es. One is he ansdiagnos ic app oach, which o e s ea men p o ocols ha can be used o a ange o emo ional diso de s. Ano he app oach is he use o he in e ne o each a la ge numbe o people who could bene i om CBT. Objec i e: This s udy aimed o analyze he e ec i eness and accep abili y o a ansdiagnos ic in e ne -deli e ed p o ocol (Emo ionRegula ion) wi h human and au oma ed guidance in pa ien s om public specialized men al heal h ca e se ings. Me hods: A 2-a med andomized con olled ial (RCT) was conduc ed o compa e he e ec i eness o Emo ionRegula ion wi h ea men as usual (TAU) in specialized men al heal h ca e. In all, 214 pa icipan s we e andomly assigned o ecei e ei he Emo ionRegula ion (n=106) o TAU (n=108). Measu emen assessmen s we e conduc ed a p e- and pos in e en ion and a a 3-mon h ollow-up. Resul s: The esul s e ealed he supe io i y o Emo ionRegula ion o e TAU on measu es o dep ession (d=0.41), anxie y (d=0.35), and heal h- ela ed quali y o li e (d=−0.45) a pos ea men , and hese gains we e main ained a he 3-mon h ollow-up. Fu he mo e, he esul s o expec a ions and opinions showed ha Emo ionRegula ion was well accep ed by pa icipan s. Conclusions: Emo ionRegula ion was mo e e ec i e han TAU o he ea men o emo ional diso de s in he Spanish public men al heal h sys em. The implica ions o his RCT, limi a ions, and sugges ions o u u e esea ch a e discussed. T ial Regis a ion: ClinicalT ials.go NCT02345668; h ps://clinical ials.go /c 2/show/NCT02345668 (J Med In e ne Res 2020;22(7):e18220) doi: 10.2196/18220 J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 1h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X KEYWORDS ansdiagnos ic; in e ne ; cogni i e beha io al he apy; emo ional diso de s; dep ession; anxie y; specialized ca e In oduc ion Diso de -Speci ic Cogni i e Beha io al The apy o Emo ional Diso de s Anxie y and dep essi e diso de s, also known as emo ional diso de s (EDs) [1], ha e he highes p e alence a es among psychological diso de s [2,3], and a e associa ed wi h subs an ial cos s [4,5] and disabili y [6,7]. In he pas h ee decades, esea ch e o s o dec ease he bu den o hese diso de s ha e led o he de elopmen and e alua ion o cogni i e beha io al ea men s in andomized con olled ials (RCTs) o each ED (ie, diso de -speci ic p o ocols), such as dep ession [8,9] and se e al anxie y diso de s, including gene alized anxie y diso de (GAD) [10,11], panic diso de (PD) and ago aphobia (AG) [12], social anxie y diso de (SAD) [13], and obsessi e compulsi e diso de (OCD) [14]. Al hough he e is a la ge body o e idence showing he e icacy and e ec i eness o diso de -speci ic cogni i e beha io al he apy (CBT), in he pas 15 yea s, an inc easing numbe o esea che s ha e ag eed ha he e a e some p oblems ha hinde he op imal deploymen o hese ea men s. The main d awback o diso de -speci ic ea men s s ems om he high como bidi y a es obse ed among anxie y diso de s and be ween anxie y diso de s and dep essi e diso de s, wi h como bidi y es ima es o hese diso de s anging be ween 40% and 80% [15,16]. Thus, because diso de -speci ic ea men p o ocols ocus on ea ing a speci ic diagnosis, he accompanying como bid diso de s do no ecei e he apeu ic a en ion [17,18]. This p oblem becomes clea e when we ake in o accoun esea ch linking como bidi y o aspec s such as g ea e se e i y [3], inc eased ch onici y a es [19], and a wo se clinical cou se [20]. Ano he p oblem wi h diso de -speci ic ea men s is ha sub h eshold symp oms ha do no mee diagnos ic h esholds o a pa icula diso de , bu migh be impo an o ea , no mally go un ea ed [17]. Simila ly, hese p o ocols do no add ess diagnoses ha do no i any speci ic ca ego y, despi e hei clinical ele ance, ha is, no o he wise speci ied (NOS) anxie y and dep essi e diso de s [15]. Finally, each diso de -speci ic ea men equi es he use o di e en handbooks and p o ocols, which inc eases he economic cos s and he amoun o aining needed o gain he knowledge and skills necessa y o co e he a ay o anxie y and dep essi e diso de s [17]. T ansdiagnos ic T ea men s o Anxie y and Dep ession T ansdiagnos ic ea men s ha e eme ged as an al e na i e o he adi ional diso de -speci ic app oach ha has domina ed CBT esea ch o he pas 30 yea s. T ansdiagnos ic ea men s ha e been de eloped and es ed in se e al RCTs o anxie y diso de s [21-24] and anxie y and dep essi e diso de s [25-27], and hei numbe con inues o g ow. Mo eo e , he e icacy and e ec i eness o ansdiagnos ic ea men s ha e been shown in di e en me a-analy ic e iews, compa ing hem wi h di e en con ol g oups, such as wai ing lis , a en ion con ol, and ea men as usual (TAU) [28-31], wi h pooled e ec sizes (Hedges g) in he medium o la ge ange o o e all measu es o anxie y (0.65-0.82) and dep ession (0.79-0.84). Mo eo e , an addi ional me a-analysis epo ed equi alen e ec s o ansdiagnos ic ea men s (g=1.06) and diso de -speci ic ea men s (d=0.95) on anxie y ou comes [32]. Howe e , hese me a-analyses include a numbe o mixed s udies o di e en o ien a ions, such as heo y-based ansdiagnos ic ea men s and ailo ed CBT. The e o e, hese s udies make i di icul o de e mine he e ec i eness o each o ien a ion (eg, he e ec i eness o heo y-based ansdiagnos ic ea men s). The e ec i eness o ansdiagnos ic ea men s has also been shown in a me a-analysis by Ga cía-Escale a e al [33], wi h pooled e ec sizes o g=0.80 o anxie y and g=0.72 o dep ession. Unlike he abo emen ioned me a-analyses, his s udy has he pa icula i y ha i only included heo y-based ansdiagnos ic ea men s. The main cha ac e is ic o heo y-based ansdiagnos ic ea men s, also known as mechanis ically ansdiagnos ic ea men s o ansdiagnos ic ea men s based on sha ed mechanisms[34], is ha hey a e designed o add ess he common psychopa hological p ocesses unde lying anxie y and dep ession. Among he mechanis ically ansdiagnos ic ea men s o EDs, he Uni ied P o ocol (UP) [35,36] s ands ou as one o he mos empi ically suppo ed ansdiagnos ic p o ocols o anxie y and dep ession [23,37,38]. The UP is a CBT ansdiagnos ic p o ocol de eloped o add ess he unde lying psychopa hological p ocesses ha a e common o anxie y and dep essi e diso de s, wi h a pa icula ocus on neu o icism, (low) ex a e sion, and emo ion dys egula ion, which ha e been shown o play a key ole in he onse and main enance o hese diso de s [39,40]. Thus, he main goal o he UP is o each pa ien s s a egies o egula e hei emo ions in a mo e adap i e way h ough he ollowing co e ea men modules: (1) p esen - ocused emo ional awa eness, (2) cogni i e lexibili y, (3) iden i ica ion and p e en ion o emo ional a oidance pa e ns, (4) inc easing awa eness and ole ance o emo ion-elici ed physical sensa ions, and (5) g aded (in e ocep i e and si ua ional) exposu e p ocedu es. The o e all e icacy o he UP was i s shown in an RCT whe e i was compa ed wi h a wai lis con ol g oup [23] and, mo e ecen ly, in a la ge RCT whe e i was compa ed wi h well-es ablished diso de -speci ic CBT p o ocols o anxie y diso de s [37]. In addi ion, some esea ch shows he long- e m e ec s o he UP [41] and i s abili y o p oduce changes in he empe amen dimensions o beha io al inhibi ion (BI) and beha io al ac i a ion (BA) [42]. BI and BA ha e been concep ualized as 2 neu ological sys ems ep esen ing mo i a ional endencies ha a e sensi i e o h ea and ewa d en i onmen al cues, espec i ely [43]. These aspec s ha e been in ima ely linked o neu o icism and nega i e a ec and ex a e sion and posi i e a ec [42]. Ano he ea men app oach ha includes p inciples o componen s ha could be use ul o a ge EDs is dialec ical beha io al he apy (DBT) [44,45]. DBT ini ially eme ged as a heo e ical model and a ea men app oach o he ea men o suicidal beha io s and bo de line pe sonali y diso de , wi h he gene al aim o eaching s a egies o change pa e ns o emo ion J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 2h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X dys egula ion [46]. O he ange o s a egies, DBT places a special emphasis on inc easing expe ien ial awa eness and accep ance (mind ulness wha and how echniques), bu i also includes beha io al s a egies such as he opposi e ac ion, designed o diminish dis ess by engaging in beha io s o ac ions opposi e o hose associa ed wi h nega i e emo ions [44]. Mo e ecen ly, DBT skills ha e been adap ed and success ully applied o se e al anxie y and dep essi e diso de s [47,48], which sugges s ha hey could be used in a ansdiagnos ic manne o imp o e he symp oma ology o hese diso de s. Fo example, DBT p inciples may be combined wi h o he e idence-based componen s (eg, componen s o he UP) o s eng hen hei e ec i eness. The s a egy o in eg a ing CBT p inciples and componen s om di e en e idence-based he apies and o ien a ions is consis en wi h he no ion o p ocess-based CBT, de ined by Ho mann and Hayes [49]. As he au ho s s a e, “mode n CBT places much less ocus on p o ocols o synd omes and mo e ocus on e idence-based p ocesses linked o e idence-based p ocedu es” [49]. In e ne -Deli e ed In e en ions In he pas wo decades, one o he mos e iden e o s made by esea che s has been o ake ad an age o he possibili ies o e ed by in o ma ion and communica ion echnologies o imp o e he assessmen and ea men o psychological diso de s. A clea example would be he use o he in e ne o inc ease he dissemina ion o empi ically suppo ed psychological ea men s o anyone in need [50]. Resea ch has shown p omising and compelling e idence ha in e ne -deli e ed psychological in e en ions a e e ec i e o a a ie y o psychosocial p oblems, including anxie y and dep essi e diso de s [51,52]. The main ad an ages o in e ne -deli e ed ea men s o e adi ional deli e y me hods (eg, ace- o- ace he apy) include widesp ead access and dissemina ion [53], a nons igma izing way o ecei ing psychological ea men [54], and inc eased cos -e ec i eness [55]. Resea ch has shown ha ansdiagnos ic in e ne -deli e ed ea men s a e mo e e ec i e han con ol g oups [29] and ha hese ea men s a e a leas as e ec i e as indi idual and g oup ace- o- ace ansdiagnos ic ea men s [33]. Howe e , mos o he exis ing li e a u e on ansdiagnos ic ea men s is limi ed o s udies conduc ed in communi y se ings, wi h ew s udies ca ied ou in public con ex s such as p ima y o specialized ca e [21]. Indeed, o ou knowledge, no ansdiagnos ic in e ne -deli e ed ea men s o anxie y and dep ession ha e been conduc ed in specialized public men al heal h ca e. This is somewha su p ising because ansdiagnos ic in e ne -deli e ed ea men s in his pa icula se ing could ha e se e al ad an ages o bo h clinicians and he pa ien s a ending hese cen e s. Fi s , anxie y and dep essi e diso de s a e diso de s wi h he highes p e alence a es [2,3]. Second, esou ces in hese se ings a e usually sca ce, which a ec s bo h he quan i y and he quali y o he men al heal h ca e p o ided [56]. Thi d, a la ge pe cen age o pa ien s wi h anxie y and dep essi e diso de s do no ecei e ea men in men al heal h ca e cen e s [57]. In he speci ic case o Spain, mos pa ien s a ending public men al heal h uni s su e om anxie y and dep essi e diso de s [58], he a io o clinical psychologis s o pa ien s is one o he lowes in Eu ope [59], and pa ien s ha e o endu e long wai lis s o ecei e ea men [60]. Fou h, ansdiagnos ic ea men s can be p o ided a a lowe cos (eg, in e ms o aining) [61]. Finally, he use o he in e ne can help imp o e men al heal h se ices, o ins ance, by educing he wai ing pe iod o ecei e ace- o- ace ea men [62] o by implemen ing hese ea men s as pa o a s epped-ca e model ha akes pa ien s’p o iles and needs in o accoun . Thus, each pa ien can be assigned he mos app op ia e ea men [63], lea ing ace- o- ace he apy o hose pa ien s who a e less likely o bene i om in e ne -deli e ed in e en ions. This S udy Taking all o his in o conside a ion, in his s udy, an RCT was conduc ed o es he e ec i eness o a ansdiagnos ic in e ne -deli e ed p o ocol o ED (Emo ionRegula ion), compa ed wi h TAU p o ided in Spanish public specialized men al heal h ca e. Emo ionRegula ion includes componen s o he UP and he skills om DBT (eg, mind ulness wha and how echniques), and i was designed o a ge a wide ange o EDs, including majo dep essi e diso de (MDD), dys hymic diso de (DD), PD, AG, SAD, GAD, OCD, anxie y NOS, and dep ession NOS. I was hypo hesized ha (1) he Emo ionRegula ion g oup would ou pe o m he TAU g oup on measu es o o e all anxie y and dep ession, empe amen (ie, BI and BA), and heal h- ela ed quali y o li e (QoL) a pos ea men ; (2) hese pos ea men changes would be main ained a ollow-up; (3) a signi ican ly g ea e clinical change would be obse ed in Emo ionRegula ion compa ed wi h TAU; and (4) pa icipan s in he Emo ionRegula ion g oup would a e he ea men as accep able (sco es on expec a ions and opinion ≥7/10). Me hods S udy Design A 2-a med RCT was conduc ed. Pa icipan s we e andomly assigned in a 1:1 a io o one o he ollowing 2 condi ions: (1) Emo ionRegula ion and (2) TAU. Pa icipan s we e s a i ied by p incipal diagnosis, pe o ming block andomiza ion in blocks o 4 o ensu e ha all he p incipal diagnoses we e equally ep esen ed ac oss condi ions. Compu e -gene a ed andom numbe sequences we e ob ained using s a is ical so wa e (Epida 4.1, Sou ceFo ge). This ask was pe o med by an independen esea che who was unawa e o he cha ac e is ics o he s udy. The s udy was conduc ed in compliance wi h he s udy p o ocol, he Consolida ed S anda ds o Repo ing T ials (CONSORT) s a emen [64,65], he CONSORT o Elec onic and Mobile HEal h Applica ions and onLine TeleHeal h guidelines [66], and he Decla a ion o Helsinki and good clinical p ac ice. A ull desc ip ion o he s udy p o ocol has been epo ed elsewhe e [67]. The RCT ob ained e hical app o al om he E hics Commi ee o Uni e si a Jaume I (Cas ellón, Spain) and he Clinical Resea ch E hics Commi ees o 3 hospi als (Conso cio Hospi ala io P o incial de Cas ellón, Hospi al Uni e si a io de la Ribe a, and Hospi al Uni e si a io Vall d’Heb on). The s udy p o ocol was egis e ed a ClinicalT ials.go (NCT02345668) on July 27, 2015. The J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 3h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X du a ion o he in e en ion pe iod was 18 weeks o pa icipan s in bo h condi ions, and pa icipan s’assessmen s we e conduc ed a p e- and pos ea men and a 3- and 12-mon h ollow-ups. Bo h he in e en ion (Emo ionRegula ion) and he assessmen ins umen s, excep he diagnos ic in e iew, we e deli e ed h ough a web pla o m designed by ou esea ch g oup [68]. All ans e ed da a we e secu ed ia Ad anced Enc yp ion S anda d-256 enc yp ion. S udy esea che s conduc ing pos ea men and ollow-up assessmen s (ie, diagnos ic in e iews) we e blinded o he pa icipan s’ ea men condi ions. To ensu e blinding o he e alua o s, pa icipan s we e in o med ha an independen esea che would con ac hem o conduc ollow-up assessmen s, and hey we e asked no o disclose he ea men condi ion o which hey had been alloca ed. This s udy epo s p e- o pos ea men da a and da a a 3-mon h ollow-up. Sample Size Se e al s udies we e conside ed o he calcula ion o he expec ed sample size [23,69,70]. On he basis o a minimum powe o 0.80 in a 1- ailed es (ie, es o di e ences be ween 2 independen means), an α o .05, and an es ima ed d opou a e o app oxima ely 30%, a sample size o 78 pa icipan s pe condi ion was de e mined o de ec a pos ea men e ec size o 0.40 (Cohen d) be ween he 2 condi ions. In addi ion, based on he li e a u e [71,72], an es ima ed d opou a e o app oxima ely 30% was expec ed. Thus, he inal sample size was se a 100 pa icipan s pe condi ion ( o al o 200 pa icipan s). The G*Powe so wa e ( e sion 3.1.9.4, Hein ich-Heine-Uni e si ä ) was used o calcula e he sample size [73]. Pa icipan s Pa icipan s we e ec ui ed om adul ou pa ien s a ending Spanish public specialized men al heal h ca e se ices (men al heal h uni s) o seek psychological and/o psychia ic ea men be ween July 2015 and June 2019. Ini ial ec ui men was pe o med by clinical psychologis s and psychia is s wo king in hese cen e s, and i ook place in 3 di e en hospi als: Conso cio Hospi ala io P o incial de Cas ellón (Cas ellón de la Plana), Hospi al Uni e si a io de la Ribe a (Valencia), and Hospi al Uni e si a io Vall d’Heb ón (Ba celona). Rec ui men was pe o med as ollows: (1) once psychia is s and clinical psychologis s had iden i ied a po en ial candida e, hey o e ed he pa ien he possibili y o pa icipa ing in he s udy and desc ibed he s udy cha ac e is ics o him o he ; (2) pa ien s who we e in e es ed in pa icipa ing ga e hei in o med w i en consen , and he clinician illed ou a documen wi h he pa icipan s’ sociodemog aphic and clinical cha ac e is ics (mo eo e , in his s age, pa icipan s we e p o ided wi h a documen con aining in o ma ion abou he s udy); (3) one o he esea che s in ol ed in he s udy con ac ed he pa icipan s by phone o schedule a ace- o- ace appoin men o e alua e eligibili y c i e ia using a s uc u ed diagnos ic in e iew; and (4) whene e a pa icipan me he eligibili y c i e ia, an independen esea che (unawa e o he s udy cha ac e is ics) was con ac ed o implemen andomiza ion, and pa icipan s comple ed he emaining assessmen ins umen s (sel - epo ed ques ionnai es) h ough web-based su eys. Pa icipan s we e selec ed based on he ollowing inclusion c i e ia: (1) aged 18 yea s o olde ; (2) abili y o unde s and and ead Spanish; (3) ha ing access o he in e ne a home and an email add ess; (4) mee ing Diagnos ic and S a is ical Manual o Men al Diso de s, Fou h Edi ion (DSM-IV) diagnos ic c i e ia [74] o ED (ie, MDD, DD, dep ession NOS, PD, AG, SAD, GAD, anxie y NOS, and OCD); (5) p o iding w i en in o med consen ; (6) no su e ing om a se e e men al diso de (schizoph enia, bipola diso de , and alcohol and/o subs ance dependence diso de ); (7) no p esen ing a high isk o suicide; (8) no su e ing om a disabling medical disease ha p e en ed he pa icipan om ca ying ou he psychological ea men ; and (9) no ecei ing ano he psychological ea men du ing he s udy (in he expe imen al g oup). Pha macological ea men was allowed, bu pa icipan s had o be aking he same dose du ing he 2 mon hs be o e en olling in he s udy. In addi ion, pa icipan s in he expe imen al g oup whose medica ion was inc eased o changed du ing he s udy pe iod we e excluded om he ial (dec eases in pha macological ea men we e accep ed). The e was no mone a y compensa ion o pa icipa ion in he s udy unde any o he ea men condi ions. Ins umen s Clinical Ou comes Diagnosis In e iew Clinical diagnoses we e ob ained using he mini-in e na ional neu opsychia ic in e iew (MINI) e sion 5.00 [75,76], a b ie s uc u ed diagnos ic psychia ic in e iew o he assessmen o key DSM-IV and In e na ional Classi ica ion o Diseases, 10 h Re ision, diagnoses. P incipal Ou comes Beck Dep ession In en o y, Second Edi ion Beck dep ession in en o y, second edi ion (BDI-II) [77,78], is a sel - epo ques ionnai e wi h 21 i ems abou he di e en symp oms cha ac e izing MDD, added oge he o ob ain he o al sco e, which can be a maximum o 63 poin s. The ins umen has shown good in e nal consis ency (α=.76-.95). The Spanish e sion also showed high in e nal consis ency (α=.87) o bo h he gene al and clinical popula ions (α=.89). C onbach α o he BDI-II in his s udy was .90. Beck Anxie y In en o y The Beck anxie y in en o y (BAI) [79,80] is a 21-i em sel - epo scale ha assesses anxie y, wi h a maximum sco e o 63 poin s. Each i em has a 4-poin se e i y scale ( om no a all o se e ely) ha add esses symp oms expe ienced du ing he p e ious week. P e ious alida ion s udies ha e shown an in e nal consis ency anging om 0.85 o 0.94 as well as con e gen and di e gen alidi y. The Spanish e sion o he BAI has demons a ed high in e nal consis ency (α=.93). C onbach α o he BAI in his s udy was .92. Seconda y Ou comes Beha io al Inhibi ion Scale and Beha io al Ac i a ion Scale The beha io al inhibi ion scale (BIS) and beha io al ac i a ion scale (BAS) [81,82] con ains 20 i ems a ed om 1 o 4, wi h J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 4h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X 7 BIS subscale i ems ha e alua e emo ional esponses o indi iduals o impending nega i e e en s and 13 BAS i ems ha e alua e he beha io al and emo ional esponses o indi iduals o po en ially posi i e e en s. The BIS and BAS ha e shown good eliabili y in indi iduals wi h EDs (α=.73-.92) and good con e gen and disc iminan alidi y as indica o s o empe amen . The in e nal consis ency o he Spanish e sion anges be ween 0.65 and 0.82. C onbach α o he BIS and BAS subscales in his s udy we e .61 and .80, espec i ely. Quali y o Li e Eu oQoL-5D-3L Ques ionnai e Quali y o li e Eu oQoL-5D-3L (EQ-5D-3L) ques ionnai e [83,84] is a gene ic ins umen ha measu es heal h- ela ed QoL and consis s o 2 pa s. Pa 1 assesses sel - epo ed p oblems in each o he ollowing 5 domains: mobili y, sel -ca e, daily ac i i ies, pain/discom o , and anxie y/dep ession. Each domain is di ided in o 3 le els o se e i y co esponding o no p oblems, some p oblems, and ex eme p oblems, yielding a popula ion-based p e e ence sco e o socie al index (SI). A o al o 243 heo e ically possible heal h s a es can be ob ained, and he SI is calcula ed on he basis o hese heal h s a es. Values ange om 1 (bes heal h s a e) o 0 (dea h). Howe e , his index may also p o ide nega i e alues ha co espond o heal h s a es pe cei ed as wo se han dea h. U ili y sco es o hese heal h s a es we e assigned using he a ailable Spanish popula ion a i s. Pa 2 eco ds he subjec s’ sel -assessed heal h on a isual analog scale (VAS), a 10-cm e ical line on which he bes and wo s imaginable heal h s a es sco e 100 and 0, espec i ely. In his s udy, heal h- ela ed QoL was assessed using he VAS. Diso de -Speci ic Measu es Diso de -speci ic symp oms we e e alua ed using 4 di e en sel - epo ques ionnai es. Symp oms o GAD we e assessed using he Penn S a e Wo y Ques ionnai e [85,86]. PD and AG symp oms we e e alua ed using he Panic Diso de Se e i y Scale, Sel -Repo ed [87,88]. SAD symp oms we e e alua ed using he Social In e ac ion Anxie y Scale [89,90], and OCD symp oms we e assessed using he Obsessi e Compulsi e In en o y-Re ised [91,92]. All 4 ins umen s ha e shown adequa e psychome ic p ope ies in bo h he o iginal and Spanish alida ions. C onbach αs o hese scales in his s udy we e .78, .89, .80, and .91, espec i ely. Mo e de ails abou hese assessmen ins umen s ha e been desc ibed elsewhe e [67]. T ea men Accep abili y Expec a ions and Opinions o T ea men Scales These ques ionnai es we e adap ed om he s udy by Bo ko ec and Nau [93]. Each scale is made up o 5 i ems, a ed om 0 (no hing a all) o 10 (comple ely), which ask how logical he ea men seems o be (How logical do you hink his ea men is?), o wha ex en i sa is ies he pa ien (How sa is ied a e you wi h he ea men ?), whe he he pa ien would ecommend i o a pe son wi h he same p oblem (To wha ex en do you eel con iden ecommending his ea men o a iend who has he same p oblems?), whe he i could be used o ea o he psychological p oblems (To wha ex en do you hink his ea men could be use ul in ea ing o he psychological p oblems?), and i s use ulness o he pa ien ’s p oblem (To wha ex en do you hink his ea men will be/was help ul o you?). The expec a ion scale was applied a e he ea men a ionale was explained. I s objec i e is o measu e subjec i e pa ien expec a ions ega ding his ea men . The opinion scale was adminis e ed when he pa ien had comple ed he ea men , and i was designed o assess sa is ac ion wi h his ea men . T ea men s Emo ionRegula ion Following andomiza ion, pa icipan s in he ea men condi ion we e con ac ed ia elephone by a esea che who p o ided ee access o Emo ionRegula ion, a 12-module ansdiagnos ic in e ne -deli e ed p o ocol o he ea men o ED, namely, MDD, DD, dep ession NOS, PD, AG, GAD, SAD, anxie y NOS, and OCD. The p o ocol is deli e ed h ough a web pla o m [68] designed by ou esea ch g oup. Access o he web pla o m is h ough a unique use name-passwo d combina ion and is a ailable 24 hou s a day. The ea men was i s de eloped as a manualized ansdiagnos ic ea men p o ocol wi h handbooks o bo h pa ien and he apis and hen adap ed o be deli e ed h ough a web-based pla o m. The web pla o m has success ully been used in p e ious RCTs explo ing he e icacy o in e ne -deli e ed ea men s o se e al diso de s, such as dep ession [94] and lying phobia [95]. The main co e componen s a e based on he UP [35,36], bu he p o ocol also con ains ea men s a egies de i ed om DBT [46]. The p incipal aim o he ea men componen s in Emo ionRegula ion is o lea n and p ac ice adap i e ways o egula e emo ions om a ansdiagnos ic pe spec i e, wi h he ollowing ea men componen s: p esen - ocused emo ional awa eness, cogni i e lexibili y, emo ional a oidance and emo ion-d i en beha io s, and exposu e p ocedu es (in e ocep i e and si ua ional). The p o ocol also con ains a module o acili a e he pa ien ’s engagemen wi h he he apy (mo i a ion o change), a module wi h psychoeduca ion abou emo ions, and a elapse p e en ion module. Rega ding he DBT componen s, g ea e emphasis was placed on he p esen - ocused emo ional awa eness componen by adap ing and including s a egies such as he wha and how echniques and he concep o adical accep ance. Mo eo e , he opposi e ac ion was in eg a ed in o he ea men as a way o add ess emo ion-d i en beha io s. Emo ionRegula ion includes a Welcome module ha con ains gene al in o ma ion abou he p o ocol and i s goals as well as ecommenda ions o bene i ing om i and 12 ea men modules (desc ibed in Table 1). The modules a e sequen ial o enable s ep-by-s ep mo emen h ough he p og am. The p og am du a ion can a y among he use s, and pa icipan s had access o he p o ocol o a maximum pe iod o 18 weeks. Mo eo e , pa icipan s we e allowed o use he p og am any ime hey wan ed du ing he ial pe iod (ie, du ing he ollow-up pe iods). Rega ding guidance, all pa icipan s in his condi ion ecei ed he apis and au oma ed suppo . The apis suppo consis ed o (1) an ini ial ace- o- ace session o explain he cha ac e is ics o he s udy and adminis e he diagnos ic in e iew o con i m he eligibili y c i e ia, (2) an ini ial phone call encou aging J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 5h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X pa icipan s o s a he in e en ion a e he baseline assessmen s had been comple ed, (3) 1 weekly b ie phone call (maximum o 10 min) du ing he ea men pe iod, and (4) a inal phone call (once he ea men had ended) o emind pa icipan s ha hey would be allowed o use he p og am a any ime du ing he ial pe iod and ha hey would be con ac ed o ollow-up assessmen s. Au oma ed suppo consis ed o 2 weekly ex messages eminding pa icipan s abou he impo ance o comple ing he homewo k asks and encou aging hem o e iew he ea men modules. Tex messages we e sen h ough a secu e web pla o m [96]. This web pla o m was only used o send ex messages (unidi ec ionally) wi h p ede ined con en s, and hey did no include pe sonal in o ma ion ha could ha e iden i ied he pa icipan s. Addi ional de ails abou he ea men and suppo p o ocols, as well as o he unc ionali ies o he web-based pla o m, ha e been published elsewhe e [67]. Finally, i is impo an o no e ha all pa icipan s in his condi ion we e allowed o con inue o ecei e TAU, bu only o moni o ing o pha macological ea men . Pa icipan s who ecei ed o he o ms o ea men du ing he s udy pe iod (eg, psychological ea men ) o who expe ienced inc eases o changes in pha macological ea men we e excluded om he analyses. Table 1. T ea men modules and hei objec i es. Objec i eModule P o ides a amewo k abou he ole o emo ion egula ion in EDa.1. In oduc ion o ea men To analyze p os and cons o changing, emphasize he impo ance o being mo i a ed, and help o es ablish signi ican li e goals. 2. Mo i a ion o change and goal se ing P o ides psychoeduca ion abou he oles and unc ions o emo ions and ains he pa ien o ack he 3 componen s o emo ional expe iences. 3. Unde s anding he ole o emo ions Aims o ain he pa ien in nonjudgmen al emo ional awa eness (ie, mind ulness wha and how skills) and he accep ance o emo ional expe iences. 4. Nonjudgmen al emo ional awa eness and accep ance o emo ional expe iences To con inue o p ac ice he accep ance o emo ional expe iences and inc ease awa eness o physical sensa ions, hough s, emo ions, and daily ac i i ies. 5. P ac icing p esen - ocused awa eness Focuses on he iden i ica ion o maladap i e ways o hinking (ie, hinking aps).6. Lea ning o be lexible Aims o each he pa ien s s a egies o modi y hinking aps (ie, cogni i e eapp aisal). I also p o ides in o ma ion abou in usi e hough s and how o deal wi h hem. 7. P ac icing cogni i e lexibili y Aims o each he pa ien s o iden i y he emo ion a oidance s a egies ha con ibu e o he main enance o ED. 8. Emo ional a oidance To lea n he concep o EDBsband eplace hei maladap i e EDB wi h o he mo e adap i e beha io s.9. Emo ion-d i en beha io s To each he ole o physical sensa ions in he emo ional esponse and p o ide aining in in e ocep i e exposu e. 10. Accep ing and acing physical sensa- ions To build exposu e hie a chies o help he pa ien s begin o ace si ua ion-elici ed a oided emo ions.11. Facing emo ions in he con ex s in which hey occu To e iew wha pa ien s ha e lea ned h oughou he p og am, schedule he u u e p ac ice o he lea ned s a egies, and each he pa ien how o iden i y and cope wi h u u e high- isk si ua ions. 12. Relapse p e en ion aED: emo ional diso de . bEDBs: emo ion-d i en beha io s. T ea men as Usual TAU was ea men as deli e ed in cu en daily p ac ice by psychia is s and clinical psychologis s in he men al heal h cen e s in Spain. TAU in his s udy was p o ided by 3 hospi als: Conso cio Hospi ala io P o incial de Cas ellón (Cas ellón de la Plana), Hospi al Uni e si a io de la Ribe a (Valencia), and Hospi al Uni e si a io Vall d’Heb on (Ba celona). To maximize he ex e nal alidi y o his RCT, pa icipan s in his condi ion we e allowed o ecei e ei he psychia ic ea men (ie, p esc ip ion and moni o ing o an idep essan and/o anxioly ic medica ion), psychological ea men (including case managemen , g oup psycho he apy, empa hic lis ening, and/o suppo i e counseling), o a combina ion o bo h. The equency o isi s du ing he 18-week ea men pe iod a ied depending on he ype o ea men (ie, psychia ic o psychological) p o ided o he pa icipan . Pa ien s in he TAU condi ion who we e al eady ecei ing any o he a o emen ioned ea men s a he ime o en ollmen we e in o med ha hey would con inue o ecei e hese se ices du ing he ea men pe iod. Fu he mo e, pa icipan s ecei ing a ea men o he han hose p o ided in he men al heal h uni we e excluded om he ial. All pa icipan s alloca ed o TAU we e o e ed ee access o he ea men pla o m a e he s udy ended. The apis s and T ea men Fideli y The ea men and suppo p o ocols we e adminis e ed by doc o al s uden s wi h a leas wo yea s o expe ience in he diagnosis, psychological assessmen , and applica ion o CBT o di e en ED. Se e al s eps we e aken o ensu e ea men ideli y. Fi s , he apis s had p e iously been ained in he applica ion o he ea men modules. Second, a suppo p o ocol J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 6h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X (ie, weekly phone calls and au oma ed ex messages) was de eloped o be applied o all he pa icipan s in he Emo ionRegula ion condi ion. This suppo p o ocol has been b ie ly desc ibed ea lie , bu mo e de ails can be ound in he s udy by González-Robles e al [67]. Thi d, o inc ease diagnosis eliabili y, all he apis s in ol ed in he pa icipan s’assessmen we e ained in he applica ion o he diagnos ic in e iew (MINI). Da a Analysis Plan All analyses we e pe o med using he S a is ical Package o Social Sciences e sion 25. Fi s , chi-squa e es s o ca ego ical da a and independen samples es s o con inuous da a we e pe o med o con i m ha he e we e no signi ican di e ences be ween he g oups a baseline on any o he sociodemog aphic and clinical a iables. In en ion- o- ea (ITT) analyses we e pe o med ollowing Newman’s guidelines [97], using maximum likelihood (ML) es ima ion h ough he expec a ion maximiza ion impu a ion me hod. To handle missing da a, we ollowed he p ocedu e sugges ed by Hai e al [98]. Fi s , we explo ed he ypes o missing da a and de e mined ha da a we e missing a he cons uc le el. On he basis o his, we concluded ha he da a we e suscep ible o impu a ion. Second, he quan i y o missing da a was analyzed o ensu e ha none o he measu es exceeded he ecommended limi s o implemen his me hod [99]. Thi d, Li le’s missing comple ely a andom (MCAR) es s we e ca ied ou o analyze he pa e n o missing da a, concluding ha all missing da a we e MCAR (X225=28.7; P=.28). Finally, a sensi i i y analysis was pe o med on he main ou comes o compa e he esul s o he pe -p o ocol sample (ie, comple e s) wi h he impu ed alues. This analysis e ealed ha he ML es ima ion was no likely o p oduce biased es ima ions in he main analyses, eaching he same conclusions in bo h he comple e s and he impu ed da ase (pe -p o ocol: FBAI (1,127)=6.1; P=.02; and FBDI (1,127)=15.54; P<.001; ITT: FBAI (1,197)=4.79; P=.03; and FBDI (1,197)=12.97; P<.001). To es he i s hypo hesis and con ol o baseline di e ences, analyses o co a iance (ANCOVAs) we e pe o med o compa e he e ec s o he g oups on measu es o anxie y, dep ession, empe amen , and heal h- ela ed QoL, aking condi ion as he be ween-subjec a iable and he p e ea men sco es as co a ia es. The use o ANCOVAs o he analysis has been ecommended by se e al au ho s as a mo e powe ul ool o analyze da a in s udies wi h andomized designs [100,101]. To es he second hypo hesis, a 2 (condi ion: Emo ionRegula ion s TAU) × 3 ( ime: p e ea men s pos ea men s 3-mon h ollow-up) mixed analysis o a iance (ANOVA) was pe o med o es whe he he di e ences be ween Emo ionRegula ion and TAU (ie, be ween-subjec s ac o s) we e main ained a ollow-up (ie, wi hin-subjec ac o ). The ollowing assump ions o he mixed ANOVA we e analyzed: no mali y (Shapi o-Wilk es ), homoscedas ici y (Le ene es ), independence (nonpa ame ic Runs es ), and sphe ici y (Mauchly es ). The deg ees o eedom we e co ec ed using G eenhouse-Geisse whene e he sphe ici y assump ion was iola ed. Mo eo e , pai wise Bon e oni-co ec ed es s we e used o pos hoc compa isons. To compu e he magni ude o bo h wi hin-g oup and be ween-g oup changes, e ec sizes (Cohen d) we e calcula ed by di iding he di e ences be ween means by he pooled SD. E ec sizes we e in e p e ed acco ding o Cohen con en ion: e ec sizes o 0.20 a e conside ed low, e ec sizes o 0.50 a e conside ed medium, and e ec sizes o 0.80 and abo e a e conside ed la ge [102]. To es he hi d hypo hesis, we explo ed he clinical signi icance o he changes achie ed by he pa icipan s as well as po en ial de e io a ion a es using Jacobson and T uax’s eliable change index (RCI) [103] o he main ou come measu es (BDI-II and BAI) in he comple e sample o pos ea men and ollow-up measu emen s. Fi s , he cu o poin s o he pos ea men and ollow-up sco es we e de e mined o be wi hin he ange o a unc ional dis ibu ion. The RCI was hen calcula ed o es he clinically signi ican change, wi h an RCI o |1.96| o g ea e (P<.05). Finally, bo h c i e ia we e aken in o accoun o classi y pa icipan s in o he ollowing 4 ca ego ies: (1) eco e ed: when he change is signi ican ly eliable (RCI≥|1.96|; P<.05) and he pos ea men sco e is loca ed wi hin he ange o he unc ional dis ibu ion (mean [SD 2]), (2) imp o ed: when he change is signi ican ly eliable bu he pos ea men sco e is below he unc ional le el, (3) no changed: when he change is no signi ican ly eliable and he pos ea men sco e does no each he unc ional le el, and (4) de e io a ed: when he change is signi ican ly eliable bu he pos ea men sco e is wo se han he p e ea men sco e. Finally, o es he ou h hypo hesis, he sco es on expec a ions and opinions we e analyzed by calcula ing means and SDs o each o he i ems on he expec a ion and opinion o ea men scales. In addi ion, 1-way ANOVAs we e pe o med o analyze he signi icance o he di e ences be ween expec a ions and opinions. Resul s Pa icipan Flow and A i ion A lowcha o he s udy pa icipan s is displayed in Figu e 1. A o al o 326 pa ien s exp essed in e es in he s udy, 281 o whom we e assessed o eligibili y. O hese 281, 67 pa icipan s we e excluded om he s udy. A o al o 214 pa icipan s we e andomized o ei he Emo ionRegula ion (n=106) o TAU (n=108). In addi ion, 7 pa ien s in each condi ion wi hd ew om he s udy be o e he p e ea men assessmen . Consequen ly, hese pa icipan s we e no included in any o he analyses. Rega ding a i ion, 35 pa icipan s in he Emo ionRegula ion condi ion (35/106, 33.0%) and 34 in he TAU condi ion (34/108, 31.5%) d opped ou o he s udy ( easons o d opou a e shown in Figu e 1). In addi ion, 3 pa icipan s in he Emo ionRegula ion condi ion had o be excluded om he ial because o a change in hei pha macological ea men du ing he ea men pe iod. Pos ea men da a we e ob ained om 63 pa icipan s (63/99, 64%) in he Emo ionRegula ion condi ion and om 67 pa icipan s (67/101, 66.3%) in he TAU condi ion. Follow-up J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 7h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X da a we e collec ed om 51 pa icipan s (51/99, 52%) in he Emo ionRegula ion condi ion and 56 pa icipan s (56/101, 55.4%) in he TAU condi ion. Finally, 99 pa icipan s in he Emo ionRegula ion g oup and 101 pa icipan s in he TAU condi ion we e included in he ITT analysis. Figu e 1. Flowcha o pa icipan s. ED: emo ional diso de ; DSM-IV-TR; Diagnos ic and S a is ical Manual o Men al Diso de s, Fou h Edi ion, Tex Re ision; ITT: in en ion- o- ea . Baseline Cha ac e is ics Pa icipan s (N=200) had a mean age o 38.44 yea s (SD 10.80; ange 18-68), and hey we e mos ly emales (138/200, 69.0%). Table 2 p o ides he sociodemog aphic and clinical cha ac e is ics o bo h condi ions a baseline. The e we e no signi ican di e ences be ween he Emo ionRegula ion and TAU g oups a baseline on any o he sociodemog aphic and clinical cha ac e is ics. Mo eo e , no signi ican di e ences we e ound o medica ion, p incipal diagnosis, numbe o como bid diagnoses, o clinical se e i y on any o he measu es. J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 8h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X Table 2. Demog aphic and clinical cha ac e is ics o he sample a baseline (N=200). P alue es (d ) X2(d ) T ea men as usual (n=101) Emo ionRegula ion egula ion (n=99) Va iable .800.25 (198)N/Aa 38.25 (11.03)38.64 (10.61)Age (yea s), mean (SD) .26N/A1.3 (1)Sex, n (%) 66 (65.3)72 (72)Female 35 (34.7)27 (27)Male .78N/A1.1 (3)Ma i al s a us, n (%) 26 (25.7)22 (22)Single 65 (64.4)63 (63)Ma ied o pa ne ed 10 (9.9)14 (14)Di o ced o widowed .35N/A2.1 (2)Educa ion, n (%) 36 (35.6)26 (26)Basic s udies 35 (34.7)41 (41)Seconda y s udies 30 (29.7)32 (32)Uni e si y s udies .77N/A3.3 (6)Occupa ion, n (%) 11 (10.9)9 (9)S uden 9 (8.9)6 (6)Housekeepe 36 (35.6)45 (45)Employed 22 (21.8)23 (23)Unemployed 17 (16.8)13 (13)O wo k 6 (5.9)3 (3)Re i ed .91N/A1.0 (4)Mon hly income (€), n (%) 28 (27.7)27 (27)None 16 (15.8)20 (20)<641.40 (US $699.45) 38 (37.6)32 (32)641.40-1282.80 (US $699.46- 1398.89) 17 (16.8)18 (18)1282.81-2565.60 (US $1398.90- 2797.78) 2 (2.0)2 (2)>2565.60 (US $2798.78) .95N/A2.7 (8)P incipal diagnosis, n (%) 26 (27.7)23 (23)GADb 13 (12.9)16 (16)AGc 5 (5.0)9 (9)PDd 4 (4.0)4 (4)SADe 12 (12.0)8 (8)OCD 22 (21.8)20 (20)MDDg 6 (5.9)7 (7)DDh 9 (8.9)10 (10)Anxie y NOSi 3 (3.0)2 (2)Dep ession NOS N/AN/AN/AComo bid diagnoses, n 1810GAD 56PD J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 9h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X [23,27,36,110-112]. Speci ically, a combina ion o he componen s o he UP and DBT egula ion skills was ound o be mo e e ec i e han TAU in ea ing ED. Second, as a as we know, his is he i s s udy o explo e a ansdiagnos ic in e ne -deli e ed ea men in public specialized men al heal h ca e. As men ioned ea lie , mos esea ch on ansdiagnos ic web-based ea men s has been conduc ed in communi y se ings, wi h a ew o hese s udies ca ied ou in p ima y ca e [108]. The esul s showed ha he in e en ion was ound o be mo e e ec i e han TAU on he measu es o gene ic dep ession, anxie y, and QoL. These esul s a e consis en wi h he li e a u e showing he supe io i y o CBT o e TAU. Fo ins ance, a me a-analysis showed ha CBT ou weighed TAU, wi h e ec sizes in he medium ange on measu es o gene ic anxie y (Hedges g=0.70) and dep ession (Hedges g=0.69) [70]. As su p ising as hese da a migh seem, he u h is ha cu en public men al heal h se ices s ill ha e o deal wi h a numbe o ba ie s ha hinde app op ia e ca e deli e y, such as excessi e wai ing imes o access men al heal h ca e [60], low equency o sessions [113], o inadequa e ollow-up ca e [56]. Mo eo e , he lack o aining in e idence-based ea men s among p o essionals u he adds o his p oblem [114]. Finally, in Spain, se e al RCTs ha e been conduc ed using he in e ne o p o ide e idence-based ea men s, showing ha hey a e e ec i e o he ea men o ED and, in pa icula , dep ession, in communi y samples [94] and p ima y ca e [115,116], and o he s a e unde way [117]. This s udy demons a ed ha an in e ne -deli e ed p o ocol o ED was e ec i e in public specialized ca e, a se ing wi h a high demand, bu much less explo ed, hus adding o he li e a u e on hese ea men s o ED. Fu he mo e, he use o TAU as he con ol condi ion may help o answe he ques ion o “whe he a new ea men o an e idence-based psycho he apy eally su passes in ou come e ec s wha is o dina ily done a a gi en clinic” [118], hus helping o make clinicians, esea che s, and policy make s awa e o he limi a ions and aspec s ha should be imp o ed in his speci ic se ing. Limi a ions Al hough he esul s o his RCT a e p omising, hey should be in e p e ed in ligh o he ollowing limi a ions. Fi s , al hough se e al measu es we e aken o minimize a i ion (eg, guidance was p o ided o all he pa ien s pa icipa ing in Emo ionRegula ion), he numbe o pa ien s who d opped ou o he s udy was high (a ound 35%). Howe e , his p opo ion was close o wha is ypically obse ed in he li e a u e on in e ne -deli e ed psychological ea men s (ie, app oxima ely 30%-35%) [71]. Mo eo e , a i ion in he TAU condi ion was simila (34/108, 31.5%). Second, his RCT was no powe ed o de ec di e ences in diso de -speci ic measu es (ie, o GAD, PD o AG, SAD, and OCD). The e o e, u u e s udies ha mee he minimum le els o s a is ical powe o de ec di e ences in hese measu es a e wa an ed. Thi d, al hough he equency o he session in TAU was low and mos pa ien s in his condi ion we e ecei ing only pha maco he apy (as obse ed by he esea che s), hese da a we e no moni o ed du ing he ial. Finally, he esul s o accep abili y (ie, expec a ions and opinions) migh no be en i ely ep esen a i e because da a om pa ien s who d opped ou o he in e en ion we e no included in hese analyses. Conclusions and Fu u e Di ec ions The e ec i eness o a mechanis ically ansdiagnos ic in e ne -deli e ed p o ocol o ED was compa ed wi h TAU in public specialized men al heal h ca e. Al hough he esul s a e p omising, mo e esea ch in specialized ca e should be conduc ed o ex end he indings ob ained in his s udy. Fi s , esea ch on p edic o s and mode a o s o ea men ou comes and d opou in his speci ic se ing can help o delinea e he p o iles o pa icipan s who a e mo e likely o bene i om hese ea men s and help o answe he classic ques ion, “wha ea men , by whom, is mos e ec i e o his indi idual wi h ha speci ic p oblem, unde which se o ci cums ances?” [119]. Mo eo e , we belie e ha he in eg a ion o p inciples om di e en e idence-based p o ocols (eg, componen s o he UP and DBT) can be a powe ul s a egy ha should guide u u e esea ch on e idence-based psycho he apy. This s a egy is in line wi h p ocess-based CBT and he new ounda ional ques ion p oposed by Ho mann and Hayes [49] ( ie, “Wha co e biopsychosocial p ocesses should be a ge ed wi h his clien gi en his goal in his si ua ion, and how can hey mos e icien ly and e ec i ely be changed?”) . Second, despi e he huge ad ances expe ienced by he ield o in e ne -deli e ed ea men s in he pas wo decades, high d opou a es emain a majo challenge in he ield. To con inue o imp o e cu en and u u e in e ne -deli e ed in e en ions, u u e s udies should s i e o include d opou s in he analysis o accep abili y using bo h quali a i e and quan i a i e app oaches. Mo eo e , o ensu e he in eg i y, quali y, and eplicabili y o hese s udies, adhe ence o exis ing esea ch guidelines is o pa amoun impo ance in his endea o . Thi d, al hough we did no assess he accep abili y o clinicians in ol ed in he RCT (ie, psychia is s, clinical psychologis s, and nu ses), i is wo h men ioning ha some o hem e used o pa icipa e in he ec ui men p ocess, which migh e lec nega i e a i udes owa d in e ne -deli e ed in e en ions among hese p o essionals. In his scena io, esea ch e o s should be made o in o m clinicians and s a e holde s abou he bene i s o in e ne -deli e ed ea men s, especially because hey a e seen as au ho i y igu es and, he e o e, hei a i udes can ha e a majo impac on pa ien s’ pe cep ions. Finally, al hough he need o e icacy s udies is ou o doub , we belie e ha i is o pa amoun impo ance o conduc mo e implemen a ion esea ch [120]. These s udies may p o ide a much deepe unde s anding o implemen a ion a iables ha can ei he acili a e o hampe he e ec i e up ake o e idence-based p o ocols in eal clinical p ac ice, such as he a i udes o clinicians and o he p o essionals owa d in e ne -deli e ed ea men s, o economical and logis ic aspec s ha a e di icul o implemen . J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 16h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X Acknowledgmen s The au ho s would like o hank Conso cio Hospi ala io P o incial de Cas ellón, Hospi al Uni e si a io de la Ribe a, and Hospi al Uni e si a io Vall d’Heb ón o hei in aluable con ibu ion o his s udy. This esea ch was conduc ed wi h he inancial suppo o g an s P1-1B2014-43 (Uni e si a Jaume I, Cas ellón), a PhD g an om he Minis y o Educa ion, Cul u e and Spo s (FPU13/00576), and CIBER Fisiopa ología de la Obesidad y Nu ición-ISCIII CB06/03/0052. The unde s had no ole in he s udy design, da a collec ion and analysis, decision o publish, o p epa a ion o he manusc ip . Con lic s o In e es None decla ed. Mul imedia Appendix 1 Desc ip i e s a is ics and e ec sizes o diso de -speci ic measu es. 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[doi: 10.1016/S0140-6736(18)32205-0] [Medline: 30314860] Abb e ia ions AG: ago aphobia ANCOVA: analysis o co a iance ANOVA: analysis o a iance BA: beha io al ac i a ion BAI: Beck Anxie y In en o y BAS: beha io al ac i a ion scale BDI-II: Beck dep ession in en o y, 2nd edi ion BI: beha io al inhibi ion BIS: beha io al inhibi ion scale CBT: cogni i e beha io al he apy CONSORT: Consolida ed S anda ds o Repo ing T ials DBT: dialec ical beha io al he apy DD: dys hymic diso de DSM-IV: Diagnos ic and S a is ical Manual o Men al Diso de s, Fou h Edi ion ED: emo ional diso de EQ-5D-3L: Eu oQoL-5D-3L ques ionnai e GAD: gene alized anxie y diso de ITT: in en ion- o- ea MCAR: missing comple ely a andom MDD: majo dep essi e diso de MINI: mini-in e na ional neu opsychia ic in e iew ML: maximum likelihood NOS: no o he wise speci ied OCD: obsessi e compulsi e diso de PD: panic diso de QoL: quali y o li e RCI: eliable change index RCT: andomized con olled ial SAD: social anxie y diso de J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 22h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X SI: socie al index TAU: ea men as usual UP: Uni ied P o ocol VAS: isual analog scale Edi ed by G Eysenbach; submi ed 14.02.20; pee - e iewed by B Sandín, L Bücke ; commen s o au ho 24.03.20; e ised e sion ecei ed 08.04.20; accep ed 08.04.20; published 07.07.20 Please ci e as: González-Robles A, Díaz-Ga cía A, Ga cía-Palacios A, Roca P, Ramos-Qui oga JA, Bo ella C E ec i eness o a T ansdiagnos ic Guided In e ne -Deli e ed P o ocol o Emo ional Diso de s Ve sus T ea men as Usual in Specialized Ca e: Randomized Con olled T ial J Med In e ne Res 2020;22(7):e18220 URL: h ps://www.jmi .o g/2020/7/e18220 doi: 10.2196/18220 PMID: ©Albe o González-Robles, Amanda Díaz-Ga cía, Azucena Ga cía-Palacios, Pablo Roca, Josep An oni Ramos-Qui oga, C is ina Bo ella. O iginally published in he Jou nal o Medical In e ne Resea ch (h p://www.jmi .o g), 07.07.2020. This is an open-access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License (h ps://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k, i s published in he Jou nal o Medical In e ne Resea ch, is p ope ly ci ed. The comple e bibliog aphic in o ma ion, a link o he o iginal publica ion on h p://www.jmi .o g/, as well as his copy igh and license in o ma ion mus be included. J Med In e ne Res 2020 | ol. 22 | iss. 7 | e18220 | p. 23h ps://www.jmi .o g/2020/7/e18220 (page numbe no o ci a ion pu poses) González-Robles e alJOURNAL OF MEDICAL INTERNET RESEARCH XSL • FO Rende X