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                                                                         ComprehensivePsychiatry106(2021)152223
                                                                        Contents lists available at ScienceDirect
                                                                    ComprehensivePsychiatry
                                                      journalhomepage:www.elsevier.com/locate/comppsych
            Cognitive behavioural therapy with exposure and response prevention
            in the treatment of obsessive-compulsive disorder: A systematic
            reviewandmeta-analysisofrandomisedcontrolledtrials
                                  a,b,                        a                              c                          d                               d
                                      ⁎
            JemmaE.Reid                 , Keith R. Laws , Lynne Drummond , Matteo Vismara , Benedetta Grancini ,
                                        a,b                             a,b,e
            Davis Mpavaenda                , Naomi A. Fineberg
            a University of Hertfordshire, Hatfield, Hertfordshire, UK
            b Hertfordshire Partnership University NHS Foundation Trust, Hertfordshire, UK
            c South West London and St George's NHS Trust, UK
            d University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, Milano, Italy
            e University of Cambridge School of Clinical Medicine, Cambridge, UK
            article info                                        abstract
            Available online xxxx                               Background: Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is
                                                                widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncer-
            Keywords:                                           tainty remainshoweveraboutthemagnitudeoftheeffectofCBTwithERPandtheimpactofmoderatingfactors
            Cognitive behavioural therapy                       in patients with OCD.
            Exposureandresponseprevention                       Method:Thissystematicreviewandmeta-analysisassessedrandomised-controlledtrialsofCBTwithERPinpa-
            researcher allegiance                               tientsofallageswithOCD.ThestudywaspreregisteredinPROSPERO(CRD42019122311).Theprimaryoutcome
            Meta-analysis                                       wasend-of-trial OCD symptomscores. The moderating effects of patient-related and study-related factors in-
            Obsessive-compulsive disorder                       cluding type of control intervention and risk of bias were examined. Additional exploratory analyses assessed
                                                                theeffects of treatment fidelity and impact of researcher allegiance.
                                                                Results: Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults)
                                                                with1005assignedtoCBTwithERPand1015tocontrolconditions.Whencomparedagainstallcontrolcondi-
                                                                tions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g=0.74: 95% CI = 0.51 to 0.97 k =
                                                                36),whichappearedtodiminishwithincreasingage.WhileCBTwithERPwasmoreeffectivethanpsychological
                                                                placebo(g=1.1395%CI0.71to1.55,k=10),itwasnomoreeffectivethanotheractiveformsofpsychological
                                                                therapy(g =−0.05:95%CI−0.27to0.16,k=8).Similarly,whereasCBTwithERPwassignificantlysuperior
                                                                whencomparedtoallformsofpharmacologicaltreatment(g=0.36:95%CI0.7to0.64,k=7),theeffectbecame
                                                                marginalwhencomparedwithadequatedosagesofpharmacotherapyforOCD(g=0.32:95%CI−0.00to0.64,
                                                                k=6).Aminorityofstudies(k=8)weredeemedtobeatlowriskofbias.Moreover,threequartersofstudies
                                                                (k=28)demonstratedsuspectedresearcherallegianceandthesestudiesreportedalargeES(g=0.95:95%CI
                                                                0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not
                                                                efficacious (g = 0.02: 95% CI −0.29 to 0.33).
                                                                Conclusions: AlargeeffectsizewasfoundforCBTwithERPinreducingthesymptomsofOCD,butdependsupon
                                                                thechoiceofcomparatorcontrol.Thismeta-analysisalsohighlightsconcernsaboutthemethodologicalrigorand
                                                                reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher
                                                                allegiance and this requires further future investigation.
                                                                           ©2021PublishedbyElsevier Inc. This is an open access article under the CC BY-NC-ND license (http://
                                                                                                                                   creativecommons.org/licenses/by-nc-nd/4.0/).
            Contents
               1. Introduction................................................................2
               2. Aims...................................................................3
               3. Method..................................................................3
              ⁎ Corresponding author at: Hertfordshire Partnership University NHS Foundation Trust, Rosanne House, Parkway, Welwyn Garden City, Hertfordshire AL8 6HG, UK.
                E-mail address: jemma.reid1@nhs.net (J.E. Reid).
            https://doi.org/10.1016/j.comppsych.2021.152223
            0010-440X/©2021PublishedbyElsevierInc.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
              J.E. Reid, K.R. Laws, L. Drummond et al.                                                                                                     Comprehensive Psychiatry 106 (2021) 152223
                       3.1. Primaryoutcome..........................................................4
                       3.2. Secondaryoutcomes.........................................................4
                                3.2.1. Sub-groups.........................................................4
                                3.2.2. Moderators.........................................................4
                       3.3. Bias................................................................4
                       3.4. Exploratoryoutcomes........................................................4
                                3.4.1.    Treatment fidelity......................................................4
                                3.4.2. Researcherallegiance....................................................4
                       3.5. Analysis..............................................................4
                 4. Results..................................................................4
                       4.1. Publicationbias...........................................................5
                       4.2. Moderatorandexploratoryanalyses.................................................5
                       4.3. Controltype............................................................5
                       4.4. Researcherallegiancebias......................................................6
                       4.5. Adultsvschildren..........................................................6
                       4.6. Groupvsindividualtherapy.....................................................7
                       4.7. Othermoderatoranalyses......................................................7
                       4.8. Riskofbias.............................................................7
                 5. Discussion.................................................................8
                 6. Conclusions............................................................... 11
                 References.................................................................. 11
              1. Introduction                                                                                  practice guidelines [7] which also concluded that CBT primarily based
                                                                                                               on behavioural techniques such as ERP has the strongest evidence
                   Obsessive Compulsive Disorder (OCD) is a highly debilitating and                            baseforefficacy.Incontrast,themorerecentlyupdatedBritishAssocia-
              disabling illness, associated with significant impairment both of the                             tionofPsychopharmacologyguidancecitesevidenceforERPmonother-
              quality of life of the affected individual and on a wider societal scale in                      apy, cognitive therapy as a monotherapy and a combination of the two
              terms of loss of productivity and functioning (Hollander et al. [1]).                            as being effective [10]. Indeed, both documents acknowledge that,
              OCD is relatively common with a 12-month prevalence of approxi-                                  based on the available evidence, we cannot yet determine which ele-
              mately 1.2% (DSM-5) [2]. The illness usually emerges in childhood or                             ments of CBT are most responsible for its success. What is, however,
              early adulthood and runs a chronic, relapsing course (Fineberg et al.                            clear is that determiningtheprecisetypeofCBTdeliveredfromreading
              [3]). Detection of OCD frequentlyoccurs late and manypatients experi-                            thedescriptionsgiveninmanyofthepublishedtreatmenttrialscanbe
              ence untreated illness for a significant length of time before receiving                          difficult. It is also evident from the variability within published studies
              treatment (Dell'Osso et al. [4]). Increasingly, evidence suggests that a                         andsubsequentmeta-analyses(seebelow)thatmodelsandstandards
              longerdurationofuntreatedillnessleadstopooreroutcomesandprog-                                    vary. Of note, a recent small study in adults (Fineberg et al. [11]) that
              nosis (Fineberg etal.) [5]. Therefore, it is of paramount importancethat                         comparedSertraline monotherapy, CBT with ERP monotherapy deliv-
              patientswithOCDreceiveappropriatetreatmentinatimelymannerto                                      eredstrictly accordingtoamanualisedprotocol,andcombination(Ser-
              reduce suffering and improve functioning.                                                        traline and CBT with ERP) therapy, found disappointing results for CBT
                   Recommendedtreatmentsfor OCD include psychological therapy                                  withERP.Whereascombinationtherapywasthemostefficacioustreat-
              with cognitive behavioural therapy (CBT) involving exposure and re-                              mentoptionat16weeks,theadvantagewasnotsustainedandsertra-
              sponseprevention(ERP)(ERPisatherapyinwhichpatientsaretaught                                      line monotherapy was both the most efficacious and cost effective
              to confront and tolerate conditions that provoke obsessions and com-                             optionatthe52weekendpoint.
              pulsionsandresistactingonthem)orpharmacotherapywithaselective                                        Previous meta-analytic evidence has largely focused on CBT rather
              serotoninreuptakeinhibitor(SSRI)ortheserotonergictricyclicclomip-                                than specifically on CBT with the ERP. For example, a recent meta-
              ramine.AsSSRIinOCDshowsapositivedose-responserelationship[6]                                     analysis of pediatric OCD by Uhre et al. [12], analysed 12 randomised
              thehighestavailabledosagesarerecommended[7].Theinfluential2005                                    controlled trials comparing CBT to wait-list, psychological placebo or
              NICE guidelines (CG31) [8], which were based on a meta-analysis of                               pill placebo. Although symptoms (as measured by change in CY-BOCS)
              existingtrialdata,advocatetheuseoflowintensitypsychologicaltreat-                                were significantly reduced by CBT (MD: -8.51, 95% CI: −10.82 to
              ments(including ERP) for adult patients with mild symptoms of OCD.                               −6.18), all trials included in the analyses were deemed to be at high
              Monotherapy with either more intensive CBT (including ERP) or an                                 risk of bias and the certainty of evidence was graded as ‘low’ or ‘very
              SSRIisrecommendedforpatientswithmoderatesymptomsorpatients                                       low’. It is important to note that some authors challenged the findings
              withmildillnesswhocannottoleratelow-intensitypsychologicaltreat-                                 on methodological grounds [13], generating a debate in the journal's
              ment,whereascombinationtherapy(SSRIandCBTwithERP)isrecom-                                        pages [14,15]. A network meta-analysis of CBT and pharmacotherapy
              mendedforpatientswithmoresevereorresistantillness.Inthecaseof                                    for adults with OCD by Skapinakis et al. [16,17] was unable to find a
              childrenandyoungpeoplewithOCD,CBTisprioritisedoverpharmaco-                                      clearadvantageofoneformoftreatmentovertheother.Thestudyiden-
              therapy, to avoid potential adverse effects of medication in this age                            tifiedthatmostofthepatientswithinthestudieswhowereallocatedto
              groupandERPiscitedastherecommendedtypeofCBT[8].However,                                          CBTwerealsotakingpharmacologicaltreatment,suggestingthatthese
              as the original analyses upon which this guidance is based is now                                wereinfact trials of combination treatment, and further highlighting
              more than 15 years old and as more data has since accrued (NICE                                  difficulties in interpreting the results from studies of CBT in OCD
              have stated support for a review of the OCD treatment guidelines)                                (Skapinakis et al. [18]).
              [8,9], it is timely to review the evidence supporting the effectiveness                              Existingmeta-analyseshaverarelyexclusivelyfocusedonERPstud-
              of CBT involving ERP across the age range in OCD.                                                ies, withmostanalysingERPinsub-groupanalysesofmultipleinterven-
                   Alarge number of individual studies, varying in quality and size,                           tions. The earliest ERP for OCD meta-analytic finding often cited is that
              have demonstrated that ERP can be an effective treatment for OCD.                                by Christensen et al. [19] who reported a large effect size (2.34), but
              ThesewerereviewedindetailintheAmericanPsychiatricAssociation                                     this was derived from a pre-post analysis of just one trial. Almost a
                                                                                                           2
            J.E. Reid, K.R. Laws, L. Drummond et al.                                                                                Comprehensive Psychiatry 106 (2021) 152223
            decade later Abramowitz (1996) [20] meta-analysed a substantial cor-              data. In particular, the limitations of previous meta-analyses relate to
            pus of 24 trials (29 samples) assessing the impact of ERP on OCD in               the assessment of pre-post effect sizes (Abramowitz [20]; Eddy et al.
            adults and reported a large effect size of 1.16 for pre-post changes.             [24]; Christensen et al. [19]) or mixing pre-post and end of trial effect
            Pre-post effect sizes however are likely to provide unreliable and in-            sizes (Kobak et al. [23]); the inclusion of small RCTs (e.g. studies by
            flatedeffect size estimations because of their lack of a control compari-          Abramowitzetal.[22]weremostly<10perarm);theexclusionofac-
            son (see Cuijpers et al. [21]). It is also notable that most studies in this      tive controls and a focus largely on comparisons with wait-list controls
            meta-analysis(17/29)hadverysmallsamples,withfewerthan10par-                       (Olatjunji et al. [29]; McGuire et al. [26]); a reliance on self-report mea-
            ticipants, which is also likely to produce less reliable findings. A second        sures (Abramowitz et al. [22]); meta-analysing small numbers of ERP
            meta-analysis by Abramowitz [22] one year later did examine                       studies (McGuire et al. [26], k = 8; Eddy et al. [24] k = 2; Abramowitz
            randomised controlled trials in adult patient samples for whom OCD                etal. [22]k=8;Ӧstetal.[28]k=7;Ӧstetal.[27],k=8;Christensen
            wastheprimarydiagnosis.Theanalysisincludedeightcomparisonsbe-                     et al. [19] k = 1), which limits the possibility of examining moderator
            tweenversionsofERPandotherpsychologicalinterventions.Thestudy                     variables (see Borenstein et al. [31]); the inclusion of non-
            reportedalargeeffect(usingCohen'sd)favouringERPwhenrelaxation                     experimental designs (e.g. Jónsson, H., & Hougaard, 2008; Rosa-
            wasusedasapsychological control treatment (d = 1.18; 2 studies),                  Alcázar et al. [25]). Some have examined only children (McGuire et al.
            whereaswhenERPwascomparedtocognitivetherapy(d=−0.19;4                             [26]; Ӧst et al. [27]), while others only adults (Abramowitz 1996 [20];
            studies) or individual components of ERP (i.e. response prevention or             Ӧst et al. [28]). Most have failed to address publication bias and earlier
            exposureonly)nosignificanteffectofERPwasfound(d=0.59;2stud-                        meta-analyses produced effect size estimates based on fixed effects
            ies). All 8 studies exceptoneusedself-reportoutcomemeasuresandin-                 models. Few existing meta-analyses have assessed study quality (e.g.
            volvedintotalonly137participantswhoreceivedERPand105controls.                     Ӧstetal.[28]usedabespokemeasureandthenexaminedthisinalim-
            AroundthesametimeKobaketal.[23] also reported a large effect size                 ited way rather than as a moderator) and none appear to have used a
            for ERP (0.99 [0.89 to 1.08]) across 36 studies; however this analysis            standardised measure risk of bias. It is also notable that, where moder-
            pooled data from within (pre-post) changes and end-point between                  atorshavebeenanalysed,previousmeta-analyseshavealsofounditdif-
            group changes. Later, another pre-post meta-analysis by Eddy et al.               ficult to confidently identify treatment or patient factors that predict a
            [24] also reported a large effect size of 1.53 for ERP in 16 studies. As          better outcome with ERP (Hezel and Simpson, 2019 [32]). Moreover,
            noted, such analyses inflate effect sizes and a further analysis was con-          as the focus of previous meta-analyses has been primarily on CBT of
            ductedcomparingERPwithcontrols,butthisincludedjust2trials and                     anyform,ratherthanonethatspecificallyincorporatesERP,littleclarity
            indicated an effect size of 1.16.                                                 exists about thesuperiorityofCBTwithERPoverotherformsofCBTfor
                In a meta-analysis involving both experimental and quasi-                     OCDacross the full age range affected. Thus, while CBT with ERP re-
            experimental designs, Rosa-Alcázar et al. [25] reported a large pooled            mainsthesuggestedpsychologicaltreatmentofchoiceforOCD[6],un-
            effect size for ERP in 13 samples (1.127, 0.80 to 1.45) and this was not          certainty exists regarding its relative efficacy, the methodological
            significantly larger than for cognitive restructuring (CR) alone (1.09)            quality and coverage of previous meta-analyses as well as the extent
            or ERP plus CR (0.998).                                                           to which patient or treatment-related factors might render CBT with
                Turningtomorerecentmeta-analyseswithsomecomponentofERP                        ERPthemostsuitableoptionforaparticularindividual.
            assessed in children, McGuire et al. [26] meta-analysed 8 randomised
            controlled trials of individually-delivered ERP tested in children only.          2. Aims
            In comparisons with non-active controls conditions (mostly waiting-
            list and relaxation therapy), they reported a large effect size (g =                 This meta-analysis aims to comprehensively evaluate the available
            1.52), althoughthiswasnolargerthanfortrialsusingcognitivetherapy                  evidence from randomised controlled trials addressing the efficacy of
            (1.41). Öst et al. [27] assessed CY-BOCS changes in pediatric OCD both            CBTwithERPasatreatmentforadultsandchildrenwithOCD.There-
            for individual and for group formats of ERP. The effect size for ERP              fore, the analysis only includes studies of CBT that incorporate ERP.
            (g =0.68(95%CI0.18–1.18,k=8)wassomewhatsmallerthanthat                            Wealsoaimtoidentify whether treatment-related or patient-related
            of McGuire et al. [26] and smaller than that for Cognitive Therapy                factors impact on the treatment-response, in order to aid clinical
            (g =1.04(95%CI0.45–1.63, k = 4)withtheeffect size for ERP + CT                    decision-making. As concerns about the methodological quality of CBT
            being even smaller and non-significant (g = 0.35 (95% CI −0.04 to                  studies have been raised in previous reviews (Olantunji et al. [29],
            0.73,k=18).Ӧstetal.[28]alsopublishedameta-analysisofadulttrials                   Skapinakis et al. [16]), we aim to conduct a ‘risk of bias’ quality assess-
            andshowedthatERPdidnotdifferinefficacyfromCBTatreducingY-                          ment. As it is evident that the CBT delivered in previous studies has
            BOCS scores at end-of-trial (0.07 [95%CI -0.15 to 0.30], k = 7) or at             shown considerable variability in quality, we also incorporate an
            follow-up (0.07 [95%CI -0.27 to 0.41; k = 4).                                     assessment of the fidelity of the CBT with ERP delivered within this
                Olatunji et al. [29] combined trials of CBT and ERP in both adults            meta-analysis. In addition, we assess studies for the presence of re-
            (k=13)andchildren(k=3),andinanassessmentof12ERPtrials,re-                         searcherallegiance(RA),definedastheresearchers'“beliefinthesupe-
            portedalargeeffectsizeof1.35(CI:0.96–1.74).However,likeMcGuire                    riorityofatreatmentandinthesuperiorvalidityofthetheoryofchange
            et al. [26], their analysis excluded trials using an active psychological         that is associated with the treatment” (Leykin & DeRubeis, 2009) [33].
            control and the majority (10/12) of control arms comprised wait-list
            controls.Theuseofwait-listgroupsinpsychotherapytrialsisalsoasso-                  3. Method
            ciated withexaggeratedeffectsizes(Furukawaetal.[30]),anditisrea-
            sonable to interpret the efficacy of CBT in such studies with caution.                This meta-analysis was pre-registered with the International Pro-
            Intriguingly, Olatunji et al. [29]werealsounabletodemonstrateanyef-               spective Register of Systematic Reviews (PROSPERO: registration num-
            fectonoutcomesofcandidatemoderatorssuchasageatonsetofsymp-                        ber CRD42019122311) as a systematic review and meta-analysis of
            toms, duration of illness, gender, number of CBT sessions or the                  cognitive behavioural therapy for OCD. We subsequently refined our
            presence of co-morbidities. However, they did find that the control                search criteria to focus exclusively on those published studies that in-
            groupmoderatedtheeffectsize,withwait-listcontrolcomparisonsre-                    cluded an ERP component within the CBT arm, as this is the form of
            vealing larger effect sizes than comparison to placebo controls.                  CBTusually recommended for OCD [7,8]. We conducted a systematic
                In summary, data from individual randomised controlled trials and             search of the literature in accordance with PRISMA guidelines (Moher
            existing meta-analyses suggest that CBT with ERP is an effective treat-           et al.) [34]. The electronic databases PubMed, PsychINFO and EMBASE
            mentmodalityforOCD.Concernsaboutmethodologicalrigorarehow-                        weresearchedforeligible studies. We also checked the reference lists
            everrepeatedlyhighlightedasalimitationoninterpretingtheavailable                  of relevant studies and previous systematic reviews for unidentified
                                                                                          3
            J.E. Reid, K.R. Laws, L. Drummond et al.                                                                          Comprehensive Psychiatry 106 (2021) 152223
            studiesandsearchedforregisteredtrialsonwww.ClinicalTrials.govand             deviations from intended interventions, missing outcome data, out-
            Google Scholar (http://scholar.google.dk). There was no lower limit          comemeasurementandbiasinselectionofthereportedresults.
            with regards to publication date and searches continued until
            April 2020.                                                                  3.4. Exploratory outcomes
               Aninclusivesearchstrategywasperformedusingtheterms:‘Cogni-
            tive behavioural therapy’ OR ‘CBT’ OR ‘exposure response prevention’             Exploratory outcomes, which emergedduringthe stage of data col-
            OR ‘ERP’ AND ‘obsessive compulsive disorder’ OR ‘OCD’ generated              lection and were therefore not preregistered at PROSPERO, included
            2265articles.Thearticleswerethenscreenedusingthefollowinginclu-              analysis of the moderating effect of treatment fidelity and the presence
            sion criteria:                                                               of researcher allegiance on effect size.
               1. Randomised controlled trials in patients with OCD involving CBT
            with ERP in at least one treatment arm and a control group (which            3.4.1. Treatment fidelity
            couldbeanalternative(non-ERP)psychologicaltreatment,psycholog-                   Basedonthedescriptionsgivenwithineachstudy,anassessmentof
            ical placebo, pharmacological treatment or wait-list).                       treatment fidelity was made by an independent CBT expert (LD). This
               2. The study employed the Yale-Brown Obsessive Compulsive Scale           involvedassessing eachofthecomponentsofERPdeemedtobeessen-
            (Y-BOCS)(orsimilarsymptomseverityscale)asanoutcomemeasure.                   tial e.g. the presence of response prevention, the exposure being
               3. Full text article published in English.                                prolonged, graded and regular, the therapy being collaborative and
               Abstracts wereinitiallyscreenedforrelevancebytwostudyauthors              the level of experience of the therapist. Each component was given a
            (JR and NF). Papers not meeting these criteria were excluded from the        score of between zero (insufficient information was available to make
            analysis. Accepted studies were then independently assessed by two           a decision) and five (awarded where the component appeared was at
            membersoftheteam(JRandMV)toevaluatewhethertheyincorpo-                       a level consistent with recognised ‘best practice’) with a maximum
            rated ERP into their treatment. Protocol- disagreements were resolved        available score of 35 (Individual scores are included in Table 1).
            bydiscussionandtheinvolvementofathirdassessor(NF).Aconsensus
            wasreached in all cases.                                                     3.4.2. Researcher allegiance
               Our inclusive search strategy located a large number of studies,              Researcher allegiance was assessed for all trials utilising the ‘re-
            whichoncloserexaminationweredeemedunsuitableastheydidnot                     searcher allegiance assessmenttool’ used by Turner et al. [36]; adapted
            have a non-ERP comparator treatment arm within their study design.           fromCuijpers et al. [37]) in a recent meta-analysis that examined psy-
            Thesestudiesweresubsequentlyextractedandexcludedfromtheanal-                 chological interventions in psychosis. Following Turner et al. (2014)
            ysis. Our aim was to include studieswhereERPwasfundamentaltothe              [36], we posed the following questions to evaluate the presence of re-
            CBTbeingapplied.Onanalysingthestudies,itwasapparentthatsignif-               searcher allegiance: Is only one of the interventions mentioned in the
            icant variability emerged in the level of description of the included ERP    title? In the introduction is one of the interventions explicitly described
            components.Therefore, where a published report stated that ERP was           as being the main experimental intervention? Was one intervention
            anintegralcomponentoftheCBTbeingdelivered,weincludeditwithin                 specificallydescribedasacontrolcondition?Isthereanexplicithypoth-
            our analysis.                                                                esis that onetreatmentisexpectedtobemoreeffectivethantheother?
                                                                                         If the answer to any of these questions was yes, the study was deemed
            3.1. Primary outcome                                                         at risk of researcher allegiance.
               Our primary outcome measure was end-of-trial OCD symptom                  3.5. Analysis
            scores in the CBT with ERP group versus the control group.
                                                                                             Data were initially extracted independently by two of the authors
            3.2. Secondary outcomes                                                      (JR and NF), and were then independently re-extracted by another au-
                                                                                         thor (KL), with differences being resolved.
            3.2.1. Sub-groups                                                                Pooled effect sizes were calculated using Comprehensive Meta-
               Sub-groupanalyseswereperformedonthestudiesstratifiedonthe                  analysis, version 3. The effect size employed was Hedges g, which is
            basisoftypeofcontrol:Threeoftheauthors(JR,NFandMV)collabora-                 thestandardiseddifferencebetweenmeans,correctedforthetendency
            tivelycategorisedallstudiesaccordingtothetypeofcontrol:activepsy-            towards overestimation in small studies (Hedges, 1981). Effect sizes
            chological treatment (e.g. cognitive therapy, EMDR), psychological           were calculated comparing end-of trial total Y-BOCS (or alternative
            placebo (e.g. stress management training), pharmacological treatment         scale) scores for the intervention and control groups. Random-effects
            (e.g. SSRI), wait-list or treatment as usual (TAU). There were nostudies     modelswereusedinallanalyses.
                                                                                                                                            2              2
            that relied on a pill placebo control. Studies were also grouped and             HeterogeneitywasexaminedbyuseofQandI statistics.AnI value
            analysed according to whether the study population comprised adults          of 0–40% suggests that heterogeneity may not be important, 30–60%
            or children.                                                                 mayrepresent moderate heterogeneity, 50–90% may represent sub-
                                                                                         stantial heterogeneity, and 75–100% may represent considerable het-
            3.2.2. Moderators                                                            erogeneity (see Higgins & Green, Cochrane Handbook, 2011 [38]).
               Potential   treatment moderators were examined including                  Publication bias was examined using the statistical techniques of
            patient-relatedfactors(age,durationofillness,OCDseverityatbaseline,          DuvalandTweedie's (2000)[39]trimandfill, which aims to estimate
            depression scores at baseline and end-point) and study-related factors       the number of missing studies within an analysis and the effect that
            (duration of treatment, control group type, details of control treatment     those studies might have on outcomes.
            within each arm, experience level of therapists delivering CBT, and in-
            formation about concurrent medication),                                      4. Results
            3.3. Bias                                                                        Followingoursearchstrategyasoutlinedabove,thirty-sixtrials[11],
                                                                                         [40-74 were included in the final analysis Fig. 1.
               EachstudywasassessedforriskofbiasusingtheCochraneriskof                       The trials involved 2020 participants (1005 receiving CBT with a
            bias tool version 2.0 (RoB2: Higgina Higgins et al. [35]) by two authors     substantive ERP component,and1015assignedtoacontrolcondition).
            (JRandMV)andanydiscrepanciesresolvedbydiscussion.TheRoB2as-                  Thecomparatorcontrolconditionswereactivepsychologicaltreatment
            sessesbiasthatmayariseacrossfivedomains:biasfromrandomisation,                (k =8),psychological placebo (k = 10), a pharmacological treatment
                                                                                       4
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...Comprehensivepsychiatry contents lists available at sciencedirect journalhomepage www elsevier com locate comppsych cognitive behavioural therapy with exposure and response prevention in the treatment of obsessive compulsive disorder a systematic reviewandmeta analysisofrandomisedcontrolledtrials b c d jemmae reid keith r laws lynne drummond matteo vismara benedetta grancini e davis mpavaenda naomi fineberg university hertfordshire hateld uk partnership nhs foundation trust south west london st george s milan department biomedical clinical sciences luigi sacco milano italy cambridge school medicine article info abstract online xxxx background cbt incorporating erp is widely recognised as psychological choice for ocd uncer keywords tainty remainshoweveraboutthemagnitudeoftheeffectofcbtwitherpandtheimpactofmoderatingfactors patients exposureandresponseprevention method thissystematicreviewandmeta analysisassessedrandomised controlledtrialsofcbtwitherpinpa researcher allegiance tientsofal...

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