STUDY PROTOCOL Open Access

The effect of IPS-modified an early interventionfor people with mood and anxiety disordersstudy protocol for a randomised clinicalsuperiority trialLone Hellstroumlm1 Per Bech2 Merete Nordentoft1 Jane Lindschou3 and Lene Falgaard Eplov1

Abstract

Background Anxiety and affective disorders can be disabling and have a major impact on the ability to work InDenmark people with a mental disorder and mainly non-psychotic disorders represent a substantial and increasingpart of those receiving disability pensions Previous studies have indicated that Individual Placement and Support(IPS) has a positive effect on employment when provided to people with severe mental illness This modified IPSintervention is aimed at supporting people with recently diagnosed anxiety or affective disorders in regaining theirability to work and facilitate their return to work or education

Aim To investigate whether an early modified IPS intervention has an effect on employment and education whenprovided to people with recently diagnosed anxiety or affective disorders in a Danish context

MethodsDesign The trial is a randomised assessor-blinded clinical superiority trial of an early modified IPSintervention in addition to treatment-as-usual compared to treatment-as-usual alone for 324 participants diagnosed withan affective disorder or anxiety disorder living in the Capital Region of Denmark The primary outcome is competitiveemployment or education at 24 months Secondary outcomes are days of competitive employment or education illnesssymptoms and level of functioning including quality of life at follow-up 12 and 24 months after baseline

Discussion If the modified IPS intervention is shown to be superior to treatment-as-usual a larger number ofdisability pensions can probably be avoided and long-term sickness absences reduced with major benefits tosociety and patients This trial will add to the evidence of how best to support peoplersquos return to employment oreducation after a psychiatric disorder

Trial registration NCT01721824

Keywords Supported employment Affective disorder Anxiety Competitive employment Mentor support

BackgroundAnxiety and affective disorders are often associated withfunctional disability and can have a major impact on theability to work [1-4] Through the 1990s depressionalone was responsible for an annual loss of US$ 17 billiondue to work absenteeism and a total cost of US$ 437billion (348 billion Euro) each year in direct and indirect

societal costs in the USA [4] In Denmark mental healthproblems account for a total of 73 billion Euro each year indirect and indirect societal costs [5] Disability pension andlong-term sickness absence account for the majority [56]A significant amount of the total sickness absence inDenmark is due to mental illness and disability pensionsare increasingly awarded due to non-psychotic mental ill-ness [67] Hence it is crucial to start initiatives to supportpatients with mental health problems in retaining or regain-ing their employment or education Correspondence lonehellstroemregionhdk

1Copenhagen University Hospital Research Unit Mental Health CentreCopenhagen Bispebjerg Bakke 23 DK-2400 Copenhagen DenmarkFull list of author information is available at the end of the article

TRIALS

copy 2013 Hellstroumlm et al licensee BioMed Central Ltd This is an open access article distributed under the terms of the CreativeCommons Attribution License (httpcreativecommonsorglicensesby20) which permits unrestricted use distribution andreproduction in any medium provided the original work is properly cited

Hellstroumlm et al Trials 2013 14442httpwwwtrialsjournalcomcontent141442

The Individual Placement and Support (IPS)-modifiedearly intervention for people with mood and anxiety dis-order (IPS-MA) is an individualised supported employmentintervention aiming at supporting people with recentlydiagnosed anxiety or affective disorders to obtain and sus-tain competitive employment through mentor support Itwas created in 2011 based on the experience of a 1-yearpilot study aspects from the supported employment inter-vention IPS and findings from the literature The methodhas never been investigated in a clinical trialA recent systematic review of randomised trials as well

as controlled non-randomised cohort studies [8] found anoverall lack of evidence concerning vocational rehabilitationfor patients with recently diagnosed bipolar disordersdepression or anxiety disorders but points to three import-ant initiatives to consider preventive interventionsreturn-to-work interventions and interventions concerningshort- or long-term loss of employment Preventive in-terventions have only been investigated for patients withdepression or depressive symptoms and show evidencein favour of individualised interventions [9-11] Consideringreturn to work interventions studies suggest that an indi-vidual intervention should be combined with work-placeinterventions in close collaboration with mental healthservices [41213] Returning to work when diagnosed withdepression anxiety or bipolar disorders is also affected bypersonal and social factors hence it is important toincorporate interventions supporting these mattersToday vocational rehabilitation mainly consists of two

different approaches pre-vocational training often re-ferred to as the train-and-place model and supportedemployment referred to as place-and-train [14] Withpre-vocational training people are trained in companyinternship programmes sheltered workshops or wage-subsidised jobs before obtaining competitive employmentSupported employment aims at a rapid search for competi-tive employment with on-going support after employmentIn Denmark pre-vocational training is still standardThe most intensively studied supported employment

intervention is IPS [1516] where job consultants are inte-grated in and act in close collaboration with the mentalhealth services Several randomised trials [1417-27] haveindicated that IPS is more effective in helping patientswith severe mental illness obtain and sustain competi-tive employment compared to traditional pre-vocationaltraining A meta-analysis [28] of four randomised trials[29-32] found that after 18 months 704 had obtainedcompetitive employment in the IPS group compared to243 in the control group In a review including 11 ran-domised trials comparing IPS to traditional pre-vocationaltraining 61 of the patients obtained competitive employ-ment in the IPS group versus 23 in the control group[15] No studies were found investigating the effect of IPSwhen provided to people with recently diagnosed affective

or anxiety disorder It is recommended that the interven-tion be modified and accommodated to psychosocial andmedical aspects and thoroughly investigated in order toshow an effect when offered to for instance patients withrecently diagnosed anxiety or affective disorders [16] Fur-ther studies are needed in order to investigate the effect ofsuch interventions in addition to mental health treatmenton peoplersquos return to workSherpa ran the pilot study from October 2010 to

September 2011 (unpublished data) during which 46patients with depression anxiety or a bipolar disorderwere referred to Sherpa from two mental health centres inCopenhagen Two mentors and a career counsellor wereemployed at the time Twenty of the participating patientshad obtained either employment or education after a me-dian of 42 months (range 1 to 8 months)The above-mentioned findings from the literature

aspects from the IPS and the experiences from the 1-yearpilot study led to the creation of IPS-MA in 2011The IPS-MA is an individualised supported employment

intervention considering personal and social factors aswell as career counselling and financial guidance Focus ison a rapid search for competitive employment or edu-cation and not sheltered workshops or long internshipprogrammes Since people with affective disorders oranxiety are treated by either their general practitionerpsychiatric private practitioner or in mental healthcentres in Denmark it is difficult to integrate IPS-MAwith treatment to the same extend as in IPS Accordingto IPS-MA mentors must have an assertive approachto mental health carers and social workers and collab-orate with mental health services as well as job centresand municipalities and thereby help coordinate servicesprovided by theseThis is the first trial comparing the effect of IPS-MA to

treatment-as-usual when provided to people with recentlydiagnosed anxiety or affective disorders The hypothesis isthat more people receiving IPS-MA will return to work oreducation compared to the control group

MethodsDesignThe Sherpa trial is a randomised assessor-blinded clin-ical superiority trial comparing IPS-MA in addition totreatment-as-usual with treatment-as-usual alone in 324patients recently diagnosed with an affective disorder oran anxiety disorder (Figure 1)

ParticipantsParticipants will be recruited from Mental HealthCentres and private practising psychiatrists within theCapital Region of Denmark from 1 October 2011 until31 January 2014 Inpatients as well as outpatients areeligible

Hellstroumlm et al Trials 2013 14442 Page 2 of 10httpwwwtrialsjournalcomcontent141442

Inclusion criteriaParticipants must be aged 18 to 60 years diagnosed bythe referring psychiatrists according to the InternationalClassification of Diseases 10th edition criteria of affectivedisorders (F30-39) or anxiety disorders (F40-41) and nothave had contact with mental health services for morethan 3 years They must have been employed or enrolledin education at some time during the past 2 yearsThey must have a pronounced wish to return to eitheremployment or education but not being ready to do sowithin the following 3 months and equal to lsquomatchgrouprsquo 2 or 3 (lsquoMatch groupsrsquo are categories used bythe job centres in Denmark [33] to estimate how farpeople are from the labour market Match group 2 re-fers to people who can participate in pre-vocationaltraining or courses but who would not be able to takean ordinary job and be off social benefits within 3months Match group 3 refers to people with problemsso severe that they cannot work or participate in pre-vocational training) Participants must have the abilityto read and understand Danish and give informed consentverbally and in writing

Exclusion criteriaParticipants will be excluded if they have somatic co-morbidity causing reduced ability to work primarylarge-scale alcohol or substance abuse a legal guardianforensic psychiatric arrangements or if they do not giveinformed consent

Recruitment and randomisationEligible patients are informed about Sherpa given thewritten information and subsequently referred to Sherpaby their psychiatrists nurse or social worker A Sherpaemployee calls the patient to make an appointment forinclusion and baseline interview The assessor will interview

the participants but a Sherpa mentor will always attendthe interview in order to manage the randomisationafter the assessor has left and inform the participantabout allocation When a participant is included in thetrial central randomisation is performed when the Sherpamentor calls the Copenhagen Trial Unit and gives therelevant participant informationRandomisation is performed according to a computer-

generated allocation sequence with a varying block sizeconcealed from the investigators The randomisation isstratified by a) four diagnoses (F31 Bipolar affectivedisorder F30 F32-39 Affective disorders F40 Phobicanxiety disorders or F41 Other anxiety disorders) andb) two match groups (match group 2 or 3)

BlindingIt is not possible to blind the participants the Sherpamentors or career counsellors practitioners and carerswho deliver the intervention However they are stronglyurged not to reveal the allocation to the rest of the researchteam The assessor and research team will be blinded to theallocated intervention group throughout the entire trialperiod Should blinding be violated a second assessor willcomplete the follow-up interview Furthermore duringstatistical analyses the two intervention groups will becoded as for example X and Y and the code will notbe broken until the research team has drawn two con-clusions one assuming X is the intervention group andY is the control group and one conclusion assumingthe opposite

InterventionsThe experimental interventionParticipants randomised to the Sherpa group will be offeredIPS-MA in addition to treatment-as-usual (see descriptionfor the control group) A Danish protocol describing the

Figure 1 Flow chart for participants in the trial

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IPS-MA method can be acquired by contacting the corre-sponding author An English version is under constructionThe IPS-MA method is based on eight principles 1) Sherpais the patientrsquos advocate not an authority or a healthcareprovider 2) the process is led by the individualrsquos goalsand focus is on patient resources 3) assistance is flex-ible without time limits and responsive to the needsof the patient 4) the goal is competitive employmentor education without pre-vocational training 5) thebelief is that returning to work is possible despite amental illness but therapeutic recommendations in termsof postponement are acknowledged 6) liaison with health-care and social workers ensures a coordinated service 7) ameaningful and realistic career plan will be developed andevaluated continuously after job start and 8) Sherpa is aninterdisciplinary team which will be reflected in the assist-ance of each individualFive basic services comprise IPS-MA

1) Individualised mentor support based on psychiatricknowledge Sherpa mentors all have a background asprofessionals in mental health services Incooperation with the participant the Sherpa mentorhelps develop a plan of action in which resourcesand problems in social life as well as working life areclarified The Sherpa mentor supports the participantin how to structure and manage everyday life renewcontact with friends andor family prepare importantmeetings and live a healthy everyday life with thedisorder The Sherpa mentors very often act as layrepresentatives for the participants at meetings at thelocal job centres or municipalities

2) Coordination of services provided by Sherpa orexternal providers Through their professional skillsSherpa mentors help avoid lack of coordination andunnecessary waiting time and make sure that allavailable services are provided Sherpa mentors havean assertive approach to mental health carers andsocial workers and thereby ensure that relevantinformation is distributed between services

3) Career counselling Professional career counsellorssupport participants in creating a realistic matchbetween their competences and the demands of thejob market Participants will be given advice on howto write a curriculum vitae and job applications onjob seeking strategies and help in practicing jobinterviews and negotiating employment contracts

4) Impartial help to clarify private economy is offeredby a consultancy firm the Settlement [34] run byvolunteers The firm consists of two employees anda group of volunteers with professional backgroundsin economics law and social counselling

5) Contact with employers to help participants obtainjobs and keep them

Participants are provided with a Sherpa mentor whowill be their mentor throughout the entire interventionperiod The search for job or education will commenceas soon as possible Mentor support will continue for aslong as needed after employment or education is startedDuring the first 6 months the participant and mentormost often meet once a week for 1 to 15 hours on averageAfter 6 months the number of contacts varies and can beby telephone or email The number and duration of con-tacts depend on the needs of the participant Each mentorhas a maximum caseload of 20 participants half of whichhave been in Sherpa for more than 6 months

Sherpa teamThe Sherpa team is an interdisciplinary team consistingof six mentors and two career counsellors Sherpa mentorsall have solid experience as health professionals in mentalhealth services and include one nurse two social workersand three occupational therapists Career counsellorshave worked as career counsellors or with recruitmentor human resources in the private business sector Sherpamentors and career counsellors work closely together andshare offices

Training and supervisionNewly appointed Sherpa mentors will have a 1-weekintroduction to working routines and will attend a 2-dayworkshop introducing the IPS-MA method Mentors withexperience in the method will conduct the introductionTeam members are furthermore obliged to participate inannual refresher coursesTeam members will have monthly supervision provided

by a trained psychologist

The control groupParticipants randomised to the control group will receivelsquotreatment-as-usualrsquo as offered by the job centres inDenmark [35] Services vary according to match group andthe participantrsquos possibilities for social support Participantsreceiving sickness benefits must attend their first meetingin the job centre within 8 weeks of sickness leave Matchgroup 2 participants attend follow-up interviews every 4weeks whereas match group 3 participants attend follow-up interviews every 3 months Participants on social secur-ity will attend job-seeking interviews every 3 monthsParticipants under the age of 30 have the right and

obligation to participate in pre-vocational trainingafter no more than 13 weeks of unemployment Pre-vocational training has to last for at least 6 monthsYoung participants must not be without some sort ofpre-vocational training for more than 4 weeks Partici-pants over the age of 30 have the right and obligationto participate in pre-vocational training after no morethan 9 months of unemployment

Hellstroumlm et al Trials 2013 14442 Page 4 of 10httpwwwtrialsjournalcomcontent141442

After an individual evaluation job centres can offercertain pre-vocational training services company internshipprogrammes in public or private companies as well as insheltered workshops wage subsidy jobs skill developmentand guidance and mentor support (often offered by acolleague who helps the participant adapt to the newworkplace regarding norms and social competences)Participants receiving sickness benefits can be providedwith gradual return to employment assistive tools a per-sonal assistant or reimbursement of sickness benefits to theemployer from the first day of sickness leave [35]

Participant withdrawalParticipants can choose to withdraw from the trial atany time during the intervention period without it havingany consequences for the treatment they will receive butthey will politely be reminded of the importance of theirparticipation Participants who choose to withdraw fromthe trial are asked to specify which aspects of the trial theywithdraw from participation in the experimental inter-vention participation in the follow-up interviews use ofdata collected at central registers or complete withdrawalincluding use of already collected data

FidelityTo ensure that the services provided by Sherpa are inconcordance with the IPS-MA method an independ-ent investigator will monitor fidelity to the IPS-MAmethod twice during the first year of the interventionand subsequently once every year Fidelity will be mon-itored using the IPS-MA Fidelity Scale (unpublishedavailable through corresponding author) by interviewingparticipants mentors and career counsellors observ-ing team-meetings and meetings between mentor andparticipant as well as examining the individual plansof action and the data management systems used TheIPS-MA Fidelity Scale was developed based on the IPSFidelity Scale [36] Core elements important to the IPS-MAmethod investigated are caseload mentorsrsquo and careercounsellorsrsquo roles interdisciplinary team with groupsupervision individualised mentor support developmentand evaluation of individual plans of action coordinationof services providing career and economic counsellingfocus on rapid search for ordinary employment or educa-tion no time limitations and individualised support forthe participants and their employers community-basedservices assertive engagement and outreach

AssessmentsParticipants will be interviewed and asked to fill inquestionnaires at baseline and at follow-up after 12 and

24 months At baseline socio-demographic informationon education income base marital status number ofchildren and somatic disease will be collectedTo confirm the diagnosis the Mini International

Neuropsychiatric Interview (MINI) [37] is used at baselineBaseline interviews will always be face-to-face mostoften in the participantsrsquo home Participants will fill inquestionnaires at home

OutcomesThe primary outcome is competitive employment (in-cluding being on rehabilitation benefits flexible jobsand wage-subsidised jobs) or education at 24 monthsInformation about employment and education will beextracted from the DREAM database [38] The databaseis administered by The National Labour Market Author-ity and contains information on employment sicknessleave and education eligible to state education grantpre-vocational training disability pension social secur-ity and sickness benefitsSecondary outcomes are 1) number of days of com-

petitive employment or education 2) level of symptomsassessed by the Hamilton Depression Scale (HAM-D6)[3940] 3) level of symptoms assessed by the HamiltonAnxiety Scale (HAM-A6) [3941] 4) level of functioningassessed by The Global Assessment of Functioning (GAF)[394243] and 5) level of health-related quality of life byThe WHO-Five Well-being Index(WHO-5) [39] Secondaryoutcomes are assessed after 12 and 24 monthsExploratory outcomes are competitive employment

(including being on rehabilitation benefits flexible jobsand wage subsidy jobs) or education at 12 months re-assignment from Match group 2 or 3 to Match group 1attending company internship programs in public or pri-vate companies as well as in sheltered workshops andinformation extracted from the DREAM databaseManic symptoms are assessed by the Bech-RafaelsenMania Scale (MAS) [3944] Social performance regard-ing four domains (socially useful activities personal andsocial relationships self-care and disturbing and aggres-sive behaviour) is assessed by The Personal and SocialPerformance (PSP) [4546] The Sheehan Disability Scale[47] measures functional level regarding social relation-ships work spare time and family Health-related qual-ity of life in terms of psychological well-being is assessedby the WHO-5 [3948] and empowerment by the Em-powerment Scale [49] The Changes Questionnaire [50]will be used to assess how motivated participants areas to seeking employment or education The ClientSatisfaction Questionnaire [51] assesses satisfaction withtreatment and the EQ-5D (EuroQol) [52] assesseshealth-related quality of life The latter of the two will beused in a future health-related cost-benefit analysis All

Hellstroumlm et al Trials 2013 14442 Page 5 of 10httpwwwtrialsjournalcomcontent141442

scales and questionnaires used for measuring outcomesare validated scales [3739-4749-52]

Register-based informationInformation on vital status use of mental health ser-vices both as in- and outpatient number of days of ad-mission sickness absence and use of social benefits willbe gathered from the DREAM database or the DanishPsychiatric Case Register (DPCR) [53] DPCR is thepatient-registry system used by the mental health ser-vices in Denmark it contains information on all hospitaladmissions number and duration outpatient contactsand deathsAn overview of all data collected and the source of

collection is shown in Table 1

All data will be handled in accordance with the DanishData Protection Agency

Training and inter-rater reliabilityThree assessors conduct the interviews Britt ReuterMorthorst (BM) Marie Loslashnberg Hansen (MLH) andLH BM and LH have a masters in health science andMLH in public health science BM has 15 years experi-ence as a nurse in mental health and is an experiencedassessor Assessors have all received the necessary train-ing in the relevant instruments All assessors have par-ticipated in joint ratings for HAM-D and HAM-A withPB Regarding the MINI MAS PSP and GAF at leastseven joint ratings have been conducted in order toensure inter-rater reliability

Table 1 Data collection at baseline and follow-up

Source of collection Assessment Baseline 12 monthsfollow-up

24 monthsfollow-up

Interview Hamilton Depression Scale (HAM-D6) x x x

Hamilton Anxiety Scale (HAM-A6) x x x

Bech-Rafaelsen Mania Scale (MAS) x x x

Personal and Social Perfomance scale (PSP) x x x

Global Assessment of Functioning (GAF) x x x

Suicidal ideation x x x

Self report Sheehan Disability Scale (SDS) x x x

Quality of life (WHO-5) x x x

Empowerment Scale x x x

Changes Questionnaire x x x

Client Satisfaction Questionnaire (CSQ) x x x

Health-related quality of life EQ-5D (EuroQol) x x x

Hospital records Number of hospital admissions x x

Length of hospital admissions x x

Use of outpatient services x x

Death (all causes) x x

Suicide x x

Dreaminterview Sociodemographic information x x x

Dream Labour market affiliation x x x

Dreaminterview Civil status x x x

DPCR First contact with mental health care x

Dreaminterview Children x x x

Dreaminterview Education x x x

Dreaminterview Cohabitation status x x x

DPCR Use of mental health service x x

Dream Number of sick days x x

Dream Use of social benefits x x

Self report Treatment and use of other service from the social and healthcare sector x

Self report Service provided by Sherpa x

DPCR The Danish Psychiatric Case Register

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For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

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Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

Inclusion criteriaParticipants must be aged 18 to 60 years diagnosed bythe referring psychiatrists according to the InternationalClassification of Diseases 10th edition criteria of affectivedisorders (F30-39) or anxiety disorders (F40-41) and nothave had contact with mental health services for morethan 3 years They must have been employed or enrolledin education at some time during the past 2 yearsThey must have a pronounced wish to return to eitheremployment or education but not being ready to do sowithin the following 3 months and equal to lsquomatchgrouprsquo 2 or 3 (lsquoMatch groupsrsquo are categories used bythe job centres in Denmark [33] to estimate how farpeople are from the labour market Match group 2 re-fers to people who can participate in pre-vocationaltraining or courses but who would not be able to takean ordinary job and be off social benefits within 3months Match group 3 refers to people with problemsso severe that they cannot work or participate in pre-vocational training) Participants must have the abilityto read and understand Danish and give informed consentverbally and in writing

Exclusion criteriaParticipants will be excluded if they have somatic co-morbidity causing reduced ability to work primarylarge-scale alcohol or substance abuse a legal guardianforensic psychiatric arrangements or if they do not giveinformed consent

Recruitment and randomisationEligible patients are informed about Sherpa given thewritten information and subsequently referred to Sherpaby their psychiatrists nurse or social worker A Sherpaemployee calls the patient to make an appointment forinclusion and baseline interview The assessor will interview

the participants but a Sherpa mentor will always attendthe interview in order to manage the randomisationafter the assessor has left and inform the participantabout allocation When a participant is included in thetrial central randomisation is performed when the Sherpamentor calls the Copenhagen Trial Unit and gives therelevant participant informationRandomisation is performed according to a computer-

generated allocation sequence with a varying block sizeconcealed from the investigators The randomisation isstratified by a) four diagnoses (F31 Bipolar affectivedisorder F30 F32-39 Affective disorders F40 Phobicanxiety disorders or F41 Other anxiety disorders) andb) two match groups (match group 2 or 3)

BlindingIt is not possible to blind the participants the Sherpamentors or career counsellors practitioners and carerswho deliver the intervention However they are stronglyurged not to reveal the allocation to the rest of the researchteam The assessor and research team will be blinded to theallocated intervention group throughout the entire trialperiod Should blinding be violated a second assessor willcomplete the follow-up interview Furthermore duringstatistical analyses the two intervention groups will becoded as for example X and Y and the code will notbe broken until the research team has drawn two con-clusions one assuming X is the intervention group andY is the control group and one conclusion assumingthe opposite

InterventionsThe experimental interventionParticipants randomised to the Sherpa group will be offeredIPS-MA in addition to treatment-as-usual (see descriptionfor the control group) A Danish protocol describing the

Figure 1 Flow chart for participants in the trial

Hellstroumlm et al Trials 2013 14442 Page 3 of 10httpwwwtrialsjournalcomcontent141442

IPS-MA method can be acquired by contacting the corre-sponding author An English version is under constructionThe IPS-MA method is based on eight principles 1) Sherpais the patientrsquos advocate not an authority or a healthcareprovider 2) the process is led by the individualrsquos goalsand focus is on patient resources 3) assistance is flex-ible without time limits and responsive to the needsof the patient 4) the goal is competitive employmentor education without pre-vocational training 5) thebelief is that returning to work is possible despite amental illness but therapeutic recommendations in termsof postponement are acknowledged 6) liaison with health-care and social workers ensures a coordinated service 7) ameaningful and realistic career plan will be developed andevaluated continuously after job start and 8) Sherpa is aninterdisciplinary team which will be reflected in the assist-ance of each individualFive basic services comprise IPS-MA

1) Individualised mentor support based on psychiatricknowledge Sherpa mentors all have a background asprofessionals in mental health services Incooperation with the participant the Sherpa mentorhelps develop a plan of action in which resourcesand problems in social life as well as working life areclarified The Sherpa mentor supports the participantin how to structure and manage everyday life renewcontact with friends andor family prepare importantmeetings and live a healthy everyday life with thedisorder The Sherpa mentors very often act as layrepresentatives for the participants at meetings at thelocal job centres or municipalities

2) Coordination of services provided by Sherpa orexternal providers Through their professional skillsSherpa mentors help avoid lack of coordination andunnecessary waiting time and make sure that allavailable services are provided Sherpa mentors havean assertive approach to mental health carers andsocial workers and thereby ensure that relevantinformation is distributed between services

3) Career counselling Professional career counsellorssupport participants in creating a realistic matchbetween their competences and the demands of thejob market Participants will be given advice on howto write a curriculum vitae and job applications onjob seeking strategies and help in practicing jobinterviews and negotiating employment contracts

4) Impartial help to clarify private economy is offeredby a consultancy firm the Settlement [34] run byvolunteers The firm consists of two employees anda group of volunteers with professional backgroundsin economics law and social counselling

5) Contact with employers to help participants obtainjobs and keep them

Participants are provided with a Sherpa mentor whowill be their mentor throughout the entire interventionperiod The search for job or education will commenceas soon as possible Mentor support will continue for aslong as needed after employment or education is startedDuring the first 6 months the participant and mentormost often meet once a week for 1 to 15 hours on averageAfter 6 months the number of contacts varies and can beby telephone or email The number and duration of con-tacts depend on the needs of the participant Each mentorhas a maximum caseload of 20 participants half of whichhave been in Sherpa for more than 6 months

Sherpa teamThe Sherpa team is an interdisciplinary team consistingof six mentors and two career counsellors Sherpa mentorsall have solid experience as health professionals in mentalhealth services and include one nurse two social workersand three occupational therapists Career counsellorshave worked as career counsellors or with recruitmentor human resources in the private business sector Sherpamentors and career counsellors work closely together andshare offices

Training and supervisionNewly appointed Sherpa mentors will have a 1-weekintroduction to working routines and will attend a 2-dayworkshop introducing the IPS-MA method Mentors withexperience in the method will conduct the introductionTeam members are furthermore obliged to participate inannual refresher coursesTeam members will have monthly supervision provided

by a trained psychologist

The control groupParticipants randomised to the control group will receivelsquotreatment-as-usualrsquo as offered by the job centres inDenmark [35] Services vary according to match group andthe participantrsquos possibilities for social support Participantsreceiving sickness benefits must attend their first meetingin the job centre within 8 weeks of sickness leave Matchgroup 2 participants attend follow-up interviews every 4weeks whereas match group 3 participants attend follow-up interviews every 3 months Participants on social secur-ity will attend job-seeking interviews every 3 monthsParticipants under the age of 30 have the right and

obligation to participate in pre-vocational trainingafter no more than 13 weeks of unemployment Pre-vocational training has to last for at least 6 monthsYoung participants must not be without some sort ofpre-vocational training for more than 4 weeks Partici-pants over the age of 30 have the right and obligationto participate in pre-vocational training after no morethan 9 months of unemployment

Hellstroumlm et al Trials 2013 14442 Page 4 of 10httpwwwtrialsjournalcomcontent141442

After an individual evaluation job centres can offercertain pre-vocational training services company internshipprogrammes in public or private companies as well as insheltered workshops wage subsidy jobs skill developmentand guidance and mentor support (often offered by acolleague who helps the participant adapt to the newworkplace regarding norms and social competences)Participants receiving sickness benefits can be providedwith gradual return to employment assistive tools a per-sonal assistant or reimbursement of sickness benefits to theemployer from the first day of sickness leave [35]

Participant withdrawalParticipants can choose to withdraw from the trial atany time during the intervention period without it havingany consequences for the treatment they will receive butthey will politely be reminded of the importance of theirparticipation Participants who choose to withdraw fromthe trial are asked to specify which aspects of the trial theywithdraw from participation in the experimental inter-vention participation in the follow-up interviews use ofdata collected at central registers or complete withdrawalincluding use of already collected data

FidelityTo ensure that the services provided by Sherpa are inconcordance with the IPS-MA method an independ-ent investigator will monitor fidelity to the IPS-MAmethod twice during the first year of the interventionand subsequently once every year Fidelity will be mon-itored using the IPS-MA Fidelity Scale (unpublishedavailable through corresponding author) by interviewingparticipants mentors and career counsellors observ-ing team-meetings and meetings between mentor andparticipant as well as examining the individual plansof action and the data management systems used TheIPS-MA Fidelity Scale was developed based on the IPSFidelity Scale [36] Core elements important to the IPS-MAmethod investigated are caseload mentorsrsquo and careercounsellorsrsquo roles interdisciplinary team with groupsupervision individualised mentor support developmentand evaluation of individual plans of action coordinationof services providing career and economic counsellingfocus on rapid search for ordinary employment or educa-tion no time limitations and individualised support forthe participants and their employers community-basedservices assertive engagement and outreach

AssessmentsParticipants will be interviewed and asked to fill inquestionnaires at baseline and at follow-up after 12 and

24 months At baseline socio-demographic informationon education income base marital status number ofchildren and somatic disease will be collectedTo confirm the diagnosis the Mini International

Neuropsychiatric Interview (MINI) [37] is used at baselineBaseline interviews will always be face-to-face mostoften in the participantsrsquo home Participants will fill inquestionnaires at home

OutcomesThe primary outcome is competitive employment (in-cluding being on rehabilitation benefits flexible jobsand wage-subsidised jobs) or education at 24 monthsInformation about employment and education will beextracted from the DREAM database [38] The databaseis administered by The National Labour Market Author-ity and contains information on employment sicknessleave and education eligible to state education grantpre-vocational training disability pension social secur-ity and sickness benefitsSecondary outcomes are 1) number of days of com-

petitive employment or education 2) level of symptomsassessed by the Hamilton Depression Scale (HAM-D6)[3940] 3) level of symptoms assessed by the HamiltonAnxiety Scale (HAM-A6) [3941] 4) level of functioningassessed by The Global Assessment of Functioning (GAF)[394243] and 5) level of health-related quality of life byThe WHO-Five Well-being Index(WHO-5) [39] Secondaryoutcomes are assessed after 12 and 24 monthsExploratory outcomes are competitive employment

(including being on rehabilitation benefits flexible jobsand wage subsidy jobs) or education at 12 months re-assignment from Match group 2 or 3 to Match group 1attending company internship programs in public or pri-vate companies as well as in sheltered workshops andinformation extracted from the DREAM databaseManic symptoms are assessed by the Bech-RafaelsenMania Scale (MAS) [3944] Social performance regard-ing four domains (socially useful activities personal andsocial relationships self-care and disturbing and aggres-sive behaviour) is assessed by The Personal and SocialPerformance (PSP) [4546] The Sheehan Disability Scale[47] measures functional level regarding social relation-ships work spare time and family Health-related qual-ity of life in terms of psychological well-being is assessedby the WHO-5 [3948] and empowerment by the Em-powerment Scale [49] The Changes Questionnaire [50]will be used to assess how motivated participants areas to seeking employment or education The ClientSatisfaction Questionnaire [51] assesses satisfaction withtreatment and the EQ-5D (EuroQol) [52] assesseshealth-related quality of life The latter of the two will beused in a future health-related cost-benefit analysis All

Hellstroumlm et al Trials 2013 14442 Page 5 of 10httpwwwtrialsjournalcomcontent141442

scales and questionnaires used for measuring outcomesare validated scales [3739-4749-52]

Register-based informationInformation on vital status use of mental health ser-vices both as in- and outpatient number of days of ad-mission sickness absence and use of social benefits willbe gathered from the DREAM database or the DanishPsychiatric Case Register (DPCR) [53] DPCR is thepatient-registry system used by the mental health ser-vices in Denmark it contains information on all hospitaladmissions number and duration outpatient contactsand deathsAn overview of all data collected and the source of

collection is shown in Table 1

All data will be handled in accordance with the DanishData Protection Agency

Training and inter-rater reliabilityThree assessors conduct the interviews Britt ReuterMorthorst (BM) Marie Loslashnberg Hansen (MLH) andLH BM and LH have a masters in health science andMLH in public health science BM has 15 years experi-ence as a nurse in mental health and is an experiencedassessor Assessors have all received the necessary train-ing in the relevant instruments All assessors have par-ticipated in joint ratings for HAM-D and HAM-A withPB Regarding the MINI MAS PSP and GAF at leastseven joint ratings have been conducted in order toensure inter-rater reliability

Table 1 Data collection at baseline and follow-up

Source of collection Assessment Baseline 12 monthsfollow-up

24 monthsfollow-up

Interview Hamilton Depression Scale (HAM-D6) x x x

Hamilton Anxiety Scale (HAM-A6) x x x

Bech-Rafaelsen Mania Scale (MAS) x x x

Personal and Social Perfomance scale (PSP) x x x

Global Assessment of Functioning (GAF) x x x

Suicidal ideation x x x

Self report Sheehan Disability Scale (SDS) x x x

Quality of life (WHO-5) x x x

Empowerment Scale x x x

Changes Questionnaire x x x

Client Satisfaction Questionnaire (CSQ) x x x

Health-related quality of life EQ-5D (EuroQol) x x x

Hospital records Number of hospital admissions x x

Length of hospital admissions x x

Use of outpatient services x x

Death (all causes) x x

Suicide x x

Dreaminterview Sociodemographic information x x x

Dream Labour market affiliation x x x

Dreaminterview Civil status x x x

DPCR First contact with mental health care x

Dreaminterview Children x x x

Dreaminterview Education x x x

Dreaminterview Cohabitation status x x x

DPCR Use of mental health service x x

Dream Number of sick days x x

Dream Use of social benefits x x

Self report Treatment and use of other service from the social and healthcare sector x

Self report Service provided by Sherpa x

DPCR The Danish Psychiatric Case Register

Hellstroumlm et al Trials 2013 14442 Page 6 of 10httpwwwtrialsjournalcomcontent141442

For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

Hellstroumlm et al Trials 2013 14442 Page 7 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

IPS-MA method can be acquired by contacting the corre-sponding author An English version is under constructionThe IPS-MA method is based on eight principles 1) Sherpais the patientrsquos advocate not an authority or a healthcareprovider 2) the process is led by the individualrsquos goalsand focus is on patient resources 3) assistance is flex-ible without time limits and responsive to the needsof the patient 4) the goal is competitive employmentor education without pre-vocational training 5) thebelief is that returning to work is possible despite amental illness but therapeutic recommendations in termsof postponement are acknowledged 6) liaison with health-care and social workers ensures a coordinated service 7) ameaningful and realistic career plan will be developed andevaluated continuously after job start and 8) Sherpa is aninterdisciplinary team which will be reflected in the assist-ance of each individualFive basic services comprise IPS-MA

1) Individualised mentor support based on psychiatricknowledge Sherpa mentors all have a background asprofessionals in mental health services Incooperation with the participant the Sherpa mentorhelps develop a plan of action in which resourcesand problems in social life as well as working life areclarified The Sherpa mentor supports the participantin how to structure and manage everyday life renewcontact with friends andor family prepare importantmeetings and live a healthy everyday life with thedisorder The Sherpa mentors very often act as layrepresentatives for the participants at meetings at thelocal job centres or municipalities

2) Coordination of services provided by Sherpa orexternal providers Through their professional skillsSherpa mentors help avoid lack of coordination andunnecessary waiting time and make sure that allavailable services are provided Sherpa mentors havean assertive approach to mental health carers andsocial workers and thereby ensure that relevantinformation is distributed between services

3) Career counselling Professional career counsellorssupport participants in creating a realistic matchbetween their competences and the demands of thejob market Participants will be given advice on howto write a curriculum vitae and job applications onjob seeking strategies and help in practicing jobinterviews and negotiating employment contracts

4) Impartial help to clarify private economy is offeredby a consultancy firm the Settlement [34] run byvolunteers The firm consists of two employees anda group of volunteers with professional backgroundsin economics law and social counselling

5) Contact with employers to help participants obtainjobs and keep them

Participants are provided with a Sherpa mentor whowill be their mentor throughout the entire interventionperiod The search for job or education will commenceas soon as possible Mentor support will continue for aslong as needed after employment or education is startedDuring the first 6 months the participant and mentormost often meet once a week for 1 to 15 hours on averageAfter 6 months the number of contacts varies and can beby telephone or email The number and duration of con-tacts depend on the needs of the participant Each mentorhas a maximum caseload of 20 participants half of whichhave been in Sherpa for more than 6 months

Sherpa teamThe Sherpa team is an interdisciplinary team consistingof six mentors and two career counsellors Sherpa mentorsall have solid experience as health professionals in mentalhealth services and include one nurse two social workersand three occupational therapists Career counsellorshave worked as career counsellors or with recruitmentor human resources in the private business sector Sherpamentors and career counsellors work closely together andshare offices

Training and supervisionNewly appointed Sherpa mentors will have a 1-weekintroduction to working routines and will attend a 2-dayworkshop introducing the IPS-MA method Mentors withexperience in the method will conduct the introductionTeam members are furthermore obliged to participate inannual refresher coursesTeam members will have monthly supervision provided

by a trained psychologist

The control groupParticipants randomised to the control group will receivelsquotreatment-as-usualrsquo as offered by the job centres inDenmark [35] Services vary according to match group andthe participantrsquos possibilities for social support Participantsreceiving sickness benefits must attend their first meetingin the job centre within 8 weeks of sickness leave Matchgroup 2 participants attend follow-up interviews every 4weeks whereas match group 3 participants attend follow-up interviews every 3 months Participants on social secur-ity will attend job-seeking interviews every 3 monthsParticipants under the age of 30 have the right and

obligation to participate in pre-vocational trainingafter no more than 13 weeks of unemployment Pre-vocational training has to last for at least 6 monthsYoung participants must not be without some sort ofpre-vocational training for more than 4 weeks Partici-pants over the age of 30 have the right and obligationto participate in pre-vocational training after no morethan 9 months of unemployment

Hellstroumlm et al Trials 2013 14442 Page 4 of 10httpwwwtrialsjournalcomcontent141442

After an individual evaluation job centres can offercertain pre-vocational training services company internshipprogrammes in public or private companies as well as insheltered workshops wage subsidy jobs skill developmentand guidance and mentor support (often offered by acolleague who helps the participant adapt to the newworkplace regarding norms and social competences)Participants receiving sickness benefits can be providedwith gradual return to employment assistive tools a per-sonal assistant or reimbursement of sickness benefits to theemployer from the first day of sickness leave [35]

Participant withdrawalParticipants can choose to withdraw from the trial atany time during the intervention period without it havingany consequences for the treatment they will receive butthey will politely be reminded of the importance of theirparticipation Participants who choose to withdraw fromthe trial are asked to specify which aspects of the trial theywithdraw from participation in the experimental inter-vention participation in the follow-up interviews use ofdata collected at central registers or complete withdrawalincluding use of already collected data

FidelityTo ensure that the services provided by Sherpa are inconcordance with the IPS-MA method an independ-ent investigator will monitor fidelity to the IPS-MAmethod twice during the first year of the interventionand subsequently once every year Fidelity will be mon-itored using the IPS-MA Fidelity Scale (unpublishedavailable through corresponding author) by interviewingparticipants mentors and career counsellors observ-ing team-meetings and meetings between mentor andparticipant as well as examining the individual plansof action and the data management systems used TheIPS-MA Fidelity Scale was developed based on the IPSFidelity Scale [36] Core elements important to the IPS-MAmethod investigated are caseload mentorsrsquo and careercounsellorsrsquo roles interdisciplinary team with groupsupervision individualised mentor support developmentand evaluation of individual plans of action coordinationof services providing career and economic counsellingfocus on rapid search for ordinary employment or educa-tion no time limitations and individualised support forthe participants and their employers community-basedservices assertive engagement and outreach

AssessmentsParticipants will be interviewed and asked to fill inquestionnaires at baseline and at follow-up after 12 and

24 months At baseline socio-demographic informationon education income base marital status number ofchildren and somatic disease will be collectedTo confirm the diagnosis the Mini International

Neuropsychiatric Interview (MINI) [37] is used at baselineBaseline interviews will always be face-to-face mostoften in the participantsrsquo home Participants will fill inquestionnaires at home

OutcomesThe primary outcome is competitive employment (in-cluding being on rehabilitation benefits flexible jobsand wage-subsidised jobs) or education at 24 monthsInformation about employment and education will beextracted from the DREAM database [38] The databaseis administered by The National Labour Market Author-ity and contains information on employment sicknessleave and education eligible to state education grantpre-vocational training disability pension social secur-ity and sickness benefitsSecondary outcomes are 1) number of days of com-

petitive employment or education 2) level of symptomsassessed by the Hamilton Depression Scale (HAM-D6)[3940] 3) level of symptoms assessed by the HamiltonAnxiety Scale (HAM-A6) [3941] 4) level of functioningassessed by The Global Assessment of Functioning (GAF)[394243] and 5) level of health-related quality of life byThe WHO-Five Well-being Index(WHO-5) [39] Secondaryoutcomes are assessed after 12 and 24 monthsExploratory outcomes are competitive employment

(including being on rehabilitation benefits flexible jobsand wage subsidy jobs) or education at 12 months re-assignment from Match group 2 or 3 to Match group 1attending company internship programs in public or pri-vate companies as well as in sheltered workshops andinformation extracted from the DREAM databaseManic symptoms are assessed by the Bech-RafaelsenMania Scale (MAS) [3944] Social performance regard-ing four domains (socially useful activities personal andsocial relationships self-care and disturbing and aggres-sive behaviour) is assessed by The Personal and SocialPerformance (PSP) [4546] The Sheehan Disability Scale[47] measures functional level regarding social relation-ships work spare time and family Health-related qual-ity of life in terms of psychological well-being is assessedby the WHO-5 [3948] and empowerment by the Em-powerment Scale [49] The Changes Questionnaire [50]will be used to assess how motivated participants areas to seeking employment or education The ClientSatisfaction Questionnaire [51] assesses satisfaction withtreatment and the EQ-5D (EuroQol) [52] assesseshealth-related quality of life The latter of the two will beused in a future health-related cost-benefit analysis All

Hellstroumlm et al Trials 2013 14442 Page 5 of 10httpwwwtrialsjournalcomcontent141442

scales and questionnaires used for measuring outcomesare validated scales [3739-4749-52]

Register-based informationInformation on vital status use of mental health ser-vices both as in- and outpatient number of days of ad-mission sickness absence and use of social benefits willbe gathered from the DREAM database or the DanishPsychiatric Case Register (DPCR) [53] DPCR is thepatient-registry system used by the mental health ser-vices in Denmark it contains information on all hospitaladmissions number and duration outpatient contactsand deathsAn overview of all data collected and the source of

collection is shown in Table 1

All data will be handled in accordance with the DanishData Protection Agency

Training and inter-rater reliabilityThree assessors conduct the interviews Britt ReuterMorthorst (BM) Marie Loslashnberg Hansen (MLH) andLH BM and LH have a masters in health science andMLH in public health science BM has 15 years experi-ence as a nurse in mental health and is an experiencedassessor Assessors have all received the necessary train-ing in the relevant instruments All assessors have par-ticipated in joint ratings for HAM-D and HAM-A withPB Regarding the MINI MAS PSP and GAF at leastseven joint ratings have been conducted in order toensure inter-rater reliability

Table 1 Data collection at baseline and follow-up

Source of collection Assessment Baseline 12 monthsfollow-up

24 monthsfollow-up

Interview Hamilton Depression Scale (HAM-D6) x x x

Hamilton Anxiety Scale (HAM-A6) x x x

Bech-Rafaelsen Mania Scale (MAS) x x x

Personal and Social Perfomance scale (PSP) x x x

Global Assessment of Functioning (GAF) x x x

Suicidal ideation x x x

Self report Sheehan Disability Scale (SDS) x x x

Quality of life (WHO-5) x x x

Empowerment Scale x x x

Changes Questionnaire x x x

Client Satisfaction Questionnaire (CSQ) x x x

Health-related quality of life EQ-5D (EuroQol) x x x

Hospital records Number of hospital admissions x x

Length of hospital admissions x x

Use of outpatient services x x

Death (all causes) x x

Suicide x x

Dreaminterview Sociodemographic information x x x

Dream Labour market affiliation x x x

Dreaminterview Civil status x x x

DPCR First contact with mental health care x

Dreaminterview Children x x x

Dreaminterview Education x x x

Dreaminterview Cohabitation status x x x

DPCR Use of mental health service x x

Dream Number of sick days x x

Dream Use of social benefits x x

Self report Treatment and use of other service from the social and healthcare sector x

Self report Service provided by Sherpa x

DPCR The Danish Psychiatric Case Register

Hellstroumlm et al Trials 2013 14442 Page 6 of 10httpwwwtrialsjournalcomcontent141442

For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

Hellstroumlm et al Trials 2013 14442 Page 7 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

After an individual evaluation job centres can offercertain pre-vocational training services company internshipprogrammes in public or private companies as well as insheltered workshops wage subsidy jobs skill developmentand guidance and mentor support (often offered by acolleague who helps the participant adapt to the newworkplace regarding norms and social competences)Participants receiving sickness benefits can be providedwith gradual return to employment assistive tools a per-sonal assistant or reimbursement of sickness benefits to theemployer from the first day of sickness leave [35]

Participant withdrawalParticipants can choose to withdraw from the trial atany time during the intervention period without it havingany consequences for the treatment they will receive butthey will politely be reminded of the importance of theirparticipation Participants who choose to withdraw fromthe trial are asked to specify which aspects of the trial theywithdraw from participation in the experimental inter-vention participation in the follow-up interviews use ofdata collected at central registers or complete withdrawalincluding use of already collected data

FidelityTo ensure that the services provided by Sherpa are inconcordance with the IPS-MA method an independ-ent investigator will monitor fidelity to the IPS-MAmethod twice during the first year of the interventionand subsequently once every year Fidelity will be mon-itored using the IPS-MA Fidelity Scale (unpublishedavailable through corresponding author) by interviewingparticipants mentors and career counsellors observ-ing team-meetings and meetings between mentor andparticipant as well as examining the individual plansof action and the data management systems used TheIPS-MA Fidelity Scale was developed based on the IPSFidelity Scale [36] Core elements important to the IPS-MAmethod investigated are caseload mentorsrsquo and careercounsellorsrsquo roles interdisciplinary team with groupsupervision individualised mentor support developmentand evaluation of individual plans of action coordinationof services providing career and economic counsellingfocus on rapid search for ordinary employment or educa-tion no time limitations and individualised support forthe participants and their employers community-basedservices assertive engagement and outreach

AssessmentsParticipants will be interviewed and asked to fill inquestionnaires at baseline and at follow-up after 12 and

24 months At baseline socio-demographic informationon education income base marital status number ofchildren and somatic disease will be collectedTo confirm the diagnosis the Mini International

Neuropsychiatric Interview (MINI) [37] is used at baselineBaseline interviews will always be face-to-face mostoften in the participantsrsquo home Participants will fill inquestionnaires at home

OutcomesThe primary outcome is competitive employment (in-cluding being on rehabilitation benefits flexible jobsand wage-subsidised jobs) or education at 24 monthsInformation about employment and education will beextracted from the DREAM database [38] The databaseis administered by The National Labour Market Author-ity and contains information on employment sicknessleave and education eligible to state education grantpre-vocational training disability pension social secur-ity and sickness benefitsSecondary outcomes are 1) number of days of com-

petitive employment or education 2) level of symptomsassessed by the Hamilton Depression Scale (HAM-D6)[3940] 3) level of symptoms assessed by the HamiltonAnxiety Scale (HAM-A6) [3941] 4) level of functioningassessed by The Global Assessment of Functioning (GAF)[394243] and 5) level of health-related quality of life byThe WHO-Five Well-being Index(WHO-5) [39] Secondaryoutcomes are assessed after 12 and 24 monthsExploratory outcomes are competitive employment

(including being on rehabilitation benefits flexible jobsand wage subsidy jobs) or education at 12 months re-assignment from Match group 2 or 3 to Match group 1attending company internship programs in public or pri-vate companies as well as in sheltered workshops andinformation extracted from the DREAM databaseManic symptoms are assessed by the Bech-RafaelsenMania Scale (MAS) [3944] Social performance regard-ing four domains (socially useful activities personal andsocial relationships self-care and disturbing and aggres-sive behaviour) is assessed by The Personal and SocialPerformance (PSP) [4546] The Sheehan Disability Scale[47] measures functional level regarding social relation-ships work spare time and family Health-related qual-ity of life in terms of psychological well-being is assessedby the WHO-5 [3948] and empowerment by the Em-powerment Scale [49] The Changes Questionnaire [50]will be used to assess how motivated participants areas to seeking employment or education The ClientSatisfaction Questionnaire [51] assesses satisfaction withtreatment and the EQ-5D (EuroQol) [52] assesseshealth-related quality of life The latter of the two will beused in a future health-related cost-benefit analysis All

Hellstroumlm et al Trials 2013 14442 Page 5 of 10httpwwwtrialsjournalcomcontent141442

scales and questionnaires used for measuring outcomesare validated scales [3739-4749-52]

Register-based informationInformation on vital status use of mental health ser-vices both as in- and outpatient number of days of ad-mission sickness absence and use of social benefits willbe gathered from the DREAM database or the DanishPsychiatric Case Register (DPCR) [53] DPCR is thepatient-registry system used by the mental health ser-vices in Denmark it contains information on all hospitaladmissions number and duration outpatient contactsand deathsAn overview of all data collected and the source of

collection is shown in Table 1

All data will be handled in accordance with the DanishData Protection Agency

Training and inter-rater reliabilityThree assessors conduct the interviews Britt ReuterMorthorst (BM) Marie Loslashnberg Hansen (MLH) andLH BM and LH have a masters in health science andMLH in public health science BM has 15 years experi-ence as a nurse in mental health and is an experiencedassessor Assessors have all received the necessary train-ing in the relevant instruments All assessors have par-ticipated in joint ratings for HAM-D and HAM-A withPB Regarding the MINI MAS PSP and GAF at leastseven joint ratings have been conducted in order toensure inter-rater reliability

Table 1 Data collection at baseline and follow-up

Source of collection Assessment Baseline 12 monthsfollow-up

24 monthsfollow-up

Interview Hamilton Depression Scale (HAM-D6) x x x

Hamilton Anxiety Scale (HAM-A6) x x x

Bech-Rafaelsen Mania Scale (MAS) x x x

Personal and Social Perfomance scale (PSP) x x x

Global Assessment of Functioning (GAF) x x x

Suicidal ideation x x x

Self report Sheehan Disability Scale (SDS) x x x

Quality of life (WHO-5) x x x

Empowerment Scale x x x

Changes Questionnaire x x x

Client Satisfaction Questionnaire (CSQ) x x x

Health-related quality of life EQ-5D (EuroQol) x x x

Hospital records Number of hospital admissions x x

Length of hospital admissions x x

Use of outpatient services x x

Death (all causes) x x

Suicide x x

Dreaminterview Sociodemographic information x x x

Dream Labour market affiliation x x x

Dreaminterview Civil status x x x

DPCR First contact with mental health care x

Dreaminterview Children x x x

Dreaminterview Education x x x

Dreaminterview Cohabitation status x x x

DPCR Use of mental health service x x

Dream Number of sick days x x

Dream Use of social benefits x x

Self report Treatment and use of other service from the social and healthcare sector x

Self report Service provided by Sherpa x

DPCR The Danish Psychiatric Case Register

Hellstroumlm et al Trials 2013 14442 Page 6 of 10httpwwwtrialsjournalcomcontent141442

For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

Hellstroumlm et al Trials 2013 14442 Page 7 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

scales and questionnaires used for measuring outcomesare validated scales [3739-4749-52]

Register-based informationInformation on vital status use of mental health ser-vices both as in- and outpatient number of days of ad-mission sickness absence and use of social benefits willbe gathered from the DREAM database or the DanishPsychiatric Case Register (DPCR) [53] DPCR is thepatient-registry system used by the mental health ser-vices in Denmark it contains information on all hospitaladmissions number and duration outpatient contactsand deathsAn overview of all data collected and the source of

collection is shown in Table 1

All data will be handled in accordance with the DanishData Protection Agency

Training and inter-rater reliabilityThree assessors conduct the interviews Britt ReuterMorthorst (BM) Marie Loslashnberg Hansen (MLH) andLH BM and LH have a masters in health science andMLH in public health science BM has 15 years experi-ence as a nurse in mental health and is an experiencedassessor Assessors have all received the necessary train-ing in the relevant instruments All assessors have par-ticipated in joint ratings for HAM-D and HAM-A withPB Regarding the MINI MAS PSP and GAF at leastseven joint ratings have been conducted in order toensure inter-rater reliability

Table 1 Data collection at baseline and follow-up

Source of collection Assessment Baseline 12 monthsfollow-up

24 monthsfollow-up

Interview Hamilton Depression Scale (HAM-D6) x x x

Hamilton Anxiety Scale (HAM-A6) x x x

Bech-Rafaelsen Mania Scale (MAS) x x x

Personal and Social Perfomance scale (PSP) x x x

Global Assessment of Functioning (GAF) x x x

Suicidal ideation x x x

Self report Sheehan Disability Scale (SDS) x x x

Quality of life (WHO-5) x x x

Empowerment Scale x x x

Changes Questionnaire x x x

Client Satisfaction Questionnaire (CSQ) x x x

Health-related quality of life EQ-5D (EuroQol) x x x

Hospital records Number of hospital admissions x x

Length of hospital admissions x x

Use of outpatient services x x

Death (all causes) x x

Suicide x x

Dreaminterview Sociodemographic information x x x

Dream Labour market affiliation x x x

Dreaminterview Civil status x x x

DPCR First contact with mental health care x

Dreaminterview Children x x x

Dreaminterview Education x x x

Dreaminterview Cohabitation status x x x

DPCR Use of mental health service x x

Dream Number of sick days x x

Dream Use of social benefits x x

Self report Treatment and use of other service from the social and healthcare sector x

Self report Service provided by Sherpa x

DPCR The Danish Psychiatric Case Register

Hellstroumlm et al Trials 2013 14442 Page 6 of 10httpwwwtrialsjournalcomcontent141442

For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

Hellstroumlm et al Trials 2013 14442 Page 7 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

For the evaluation of inter-rater reliability the intra-class coefficient was used [54] The level of significancewas a coefficient of 070 or higherLH has participated in joint HAM-D6 and HAM-A6

rating sessions with PB In total 28 joint sessions be-tween PB and LH were evaluated and for HAM-D6 theintra-class coefficient was 081 (P lt 0001) Together LHand BM have seen seven patients in joint trainingsessions intra-class correlations were PSP = 092 GAF-Functioning = 084 GAF-Symptoms = 075

Power and sample sizeWe have been unable to find data on how many peopleactually return to employment or education with trad-itional pre-vocational training after anxiety or anaffective disorder in either the Danish or the national lit-erature Therefore we have leaned towards the findingsin OPUS a programme in which young people withschizophrenia receive early intensive treatment for 24months In OPUS it was found that 40 returned to em-ployment or education versus 32 in the control group(Merete Nordentoft personal communication) Based onthis knowledge we conservatively estimate that 30 willregain employment or education following traditionalpre-vocational trainingAcross a broad range of studies of severe mental ill-

ness and IPS versus traditional pre-vocational trainingstudies show that approximately 50 more of the partic-ipants in the IPS groups regain employment comparedto the control groups [15] We therefore expect to findthat 50 more of the participants in the Sherpa groupcompared to the control group will regain employmentor education and have estimated the true difference inthe experimental and control group to be 15-pointshence 45 of the participants in the Sherpa group willregain employment To be able to reject the null hypoth-esis that the proportion of participants who regain em-ployment or education in the experimental and controlgroup is equal with a probability (power) of 80 162participants will be required in each group (total 324)The Type I error probability associated with the test of

this null hypothesis is 5 We also estimated the samplesize using a power of 90 This resulted in a total of 434participants (2 times 217) We therefore plan to recruit aminimum of 324 participants and in order to reduce therisk of type II error we will aim to recruit up to 434 par-ticipants if possible in the 2-year recruitment periodPower and sample size calculations have been madeusing the PS Power and Sample Size Calculations pro-gram version 3014 [5556]The power for the secondary outcomes has been esti-

mated based on a number of 162 participants in eachgroup (Table 2) Since it has not been possible to findstudies or trials similar to our trial regarding patient groupor method expected effect size concerning number ofdays in employment or education has been conservativelyestimated The studies found [1919212257-59] did notfind any difference between groups after 12 months con-sidering GAF-F WHO-5 HAM-D6 or HAM-A6 If wefind a difference between groups we want it to be clinic-ally relevant therefore the effect sizes equals the clinicallyrelevant difference

Statistical analysesData analyses will be based on the intention-to-treatprinciple which means that data will be included in thegroup to which the participant was randomised regardlessof intervention received Data will be analysed using theIBM SPSS Statistics version 20 for WindowsTo assess homogeneity of the two groups at baseline

demographic data such as age gender marital statuseducation level support (social benefits social securityand so forth) diagnosis and Match group at baselinewill be presentedDichotomous outcomes will be analysed using logistic

regression For primary and secondary outcomes anunadjusted analysis of the effect of the Sherpa methodas an add-on to treatment-as-usual versus exclusivelytreatment-as-usual will be carried out as well as an analysisadjusted for stratification variables (diagnosis and Matchgroup) Multiple multivariate imputations will be usedto impute a distribution of missing values

Table 2 Power calculations for secondary outcomes calculated from a sample size of 324 participants

Measure Mean difference Standard deviationof the pooled mean

Type Ierror

Reference Power

No of days of competitive employmentof education at 12 months

60 days 150 days 5 Kin W 2008 [21] Burns 2007 [14] 95

GAF-F 5 15 5 Hoffmann 2011 [19] Howard 2010 [58] 85

WHO-5 10 19 5 Latimer 2006 [22] Burns 2009 [14] 99

HAM-D6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

HAM-A6 2 4 5 Wang 2007 [10] Lexis 2011 [9]Brouwers 2006 [1] Van Oostrom 2010 [59]

99

GAF Global Assessment of Functioning HAM-A6 Hamilton Anxiety Scale HAM-D6 Hamilton Depression Scale WHO-5 WHO-Five Well-being Index

Hellstroumlm et al Trials 2013 14442 Page 7 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

Continuous outcomes will be analysed in a mixed modelwith repeated measurements This model is based on theassumption that data are missing at random or missingcompletely at random [60]

FeasibilityIn 2010 11712 inpatient visits were registered in theMental Health Care Centres of the Capital Region ofDenmark not including emergency wards [61] During thesame period of time there were 4538 first-time psychiatricemergency ward visits in the Capital Region of Denmark[61] Based on these figures we find it realistic to include aminimum of 324 participants from 1 October 2011 until31 December 2013Each mentor has a maximum caseload of 20 participants

per year six mentors are currently engaged in SherpaThus it is also realistic regarding the capacity of Sherpamentors to include and complete the intervention for162 participants in 3 years

Ethical considerationsAll participants in this trial randomised to experimentalas well as control group are offered treatment accordingto best practice The trial will follow international ethicalguidelines of informed consent in clinical trials Partici-pants will receive written and verbal information aboutthe trial so as to be able to give an informed consentConsent has to be given verbally and in writing Partici-pation is voluntary and participants can withdraw theirconsent at any time during the trial without it havingany consequences for their treatment Previous trialshave not found any risks or adverse reactions to the sup-ported employment intervention [19316263] If any ofthe participants present suicidal ideations the mentorand assessor will make sure that they can be distractedfrom these thoughts have a crisis plan are not aloneafter the interview and if in doubt of any of the abovethey will offer to follow the participant to the psychiatricemergency wardThe trial protocol was submitted to the Regional

Ethics Committees of the Capital Region for review(journal no H-2-2011-FSP20) The committee assessed theprotocol to be exempt from formal approval since it is nota biomedical trial The trial has been reported to the DanishData Protection Agency (RHP journal no 2007-58-0015local journal no RHP-2011-20) and has been registeredat httpwwwclinicaltrialsgov identifier NCT01721824

Trial statusThe trial is on-going 290 participants have been rando-mised and recruitment continues until 31 January 2014

DiscussionThe IPS-MA method is based on a 1-year pilot studyand the evidence supporting IPS in other countries Toour knowledge this is the first trial investigating the effectof a supported employment intervention when providedto people with a recently diagnosed affective disorderor anxiety disorder an area with only sparse knowledgeabout effective interventions A strength of the study isthe centralised computer-based randomisation which en-sures an adequate generation of the allocation sequenceand adequate allocation concealment The use of blindedoutcome assessors for the primary outcome and the factthat it is a register-based outcome as well as the use ofintention-to-treat analysis decreases the risk of biased effectestimates The trial is registered at httpwwwclinicaltrialsgov which helps preventing selective and incomplete out-come reporting The primary outcome is register-basedwhich ensures almost complete follow-up due to thecomprehensiveness of Danish registersThe fact that we monitor fidelity to the IPS-MA method

on a yearly basis is another strength of this trial We doso to ensure that mentors and career counsellors aretrue to the methodA limitation to this trial is that we are not able to blind

participants mentors or carers Some might argue thatit is difficult to sustain the blinding of the assessor dur-ing follow-up and this is certainly a risk of bias Shouldblinding be violated a second assessor will complete thefollow-up interviewEven though participants are recruited from mental

health centres throughout the Capital Region of Denmarkand should be fairly representative of the population in theregion we may have a reduced external validity As it is thestaff at the mental health centres that identify eligible par-ticipants not everybody with an affective disorder or anx-iety disorder eligible might have been asked to participatepatients are not systematically screened for eligibilityDue to differences in labour markets and well-fare

systems results may not be directly generalisable toother countries

Impact of the resultsThe results of this trial will add to the limited knowledgeregarding vocational rehabilitation for people with recentlydiagnosed anxiety or affective disorders If potential positiveresults can be confirmed in other trials the IPS-MAmethod can be implemented at the job centres nationwideand would probably prevent a large number of disabilitypensions and long-term sickness absences with major bene-fits to society and patients

IPS-MACompeting interestsLHrsquos PhD is exclusively founded by the Obel FamilyFoundation Due to administrative convenience PhD

Hellstroumlm et al Trials 2013 14442 Page 8 of 10httpwwwtrialsjournalcomcontent141442

student LH was formally employed by Sherpa from 1June 2011 until 31 August 2013 LH has throughoutthe entire period been working at the Research Unit atMental Health Centre Copenhagen where she is nowemployed Managerial responsibility and supervision liewith LFE and PB Sherpa has had no role in the trial designand will have no role in collection of data analysis of datadata interpretation or in publication of data from the trialNone of the other authors have any competing interest

AbbreviationsDPCR Danish psychiatric case register GAF Global assessment of functioningHAM-A6 Hamilton anxiety scale HAM-D6 Hamilton depression scaleIPS Individual placement and support IPS-MA IPS-modified early interventionfor people with mood and anxiety disorder MAS The Bech-Rafaelsen maniascale MINI Mini international neuropsychiatric interview PSP Personal andsocial performance WHO-5 WHO-Five well-being index

Competing interestsThe authors declared that they have no competing interests

Authorsrsquo contributionsLFE conceived the trial participated in the planning and design and readand critically revised the manuscript for important intellectual content LHparticipated in the planning and design of the trial conducted the researchinterviews drafted the manuscript and along with LFE critically revised it forimportant intellectual content MN participated in the planning and designof the trial and has read and critically revised the manuscript JL participatedin the planning and design of the trial and has read and critically revisedthe manuscript PB participated in the planning and design of the trial wasresponsible of the training of the assessors and has read and criticallyrevised the manuscript All authors read and approved the final version ofthe manuscript

AcknowledgementsBritt Reuter Morthorst and Marie Loslashnberg Hansen for excellent assistance inrecruiting participants conducting research interviews and data assessmentAnn-Lis Gregersen for among many other things patiently contactingparticipants for follow-up

FundingThe trial as a whole is founded by the Obel Family Foundation the TrygFoundation and the National Labour Market Authority No current or futuresponsors of the trial will have any role in the trial design collection of dataanalysis of data data interpretation or in publication of data from the trial

Author details1Copenhagen University Hospital Research Unit Mental Health CentreCopenhagen Bispebjerg Bakke 23 DK-2400 Copenhagen Denmark2Psychiatric Research Unit Mental Health Centre North Zealand Dyrehavevej48 3400 Hilleroslashd Denmark 3Department 3344 Copenhagen Trial UnitCentre for Clinical Intervention Research Rigshospitalet CopenhagenUniversity Hospital Blegdamsvej 9 DK-2100 Copenhagen Oslash Denmark

Received 28 June 2013 Accepted 10 December 2013Published 24 December 2013

References1 Brouwers EP Tiemens BG Terluin B Verhaak PF Effectiveness of an

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2 Nieuwenhuijsen K Bultmann U Neumeyer-Gromen A Verhoeven AC VerbeekJH van der Feltz-Cornelis CM Interventions to improve occupational healthin depressed people Cochrane Database Syst Rev 2008 2CD006237

3 Rebergen DS Bruinvels DJ Bezemer PD van der Beek AJ van MWGuideline-based care of common mental disorders by occupationalphysicians (CO-OP study) a randomized controlled trial J Occup EnvironMed 2009 51305ndash312

4 Schene AH Koeter MW Kikkert MJ Swinkels JA McCrone P Adjuvantoccupational therapy for work-related major depression works randomizedtrial including economic evaluation Psychol Med 2007 37351ndash362

5 Borg V Andersen Nexoslash M Kolte I Andersen M White book on mentalhealth sickness absence and return to work [Hvidbog om mentalt helbredsygefravaeligr og tilbagevenden til arbejde] Copenhagen The National ResearchCentre for the Working Environment 2010

6 Statistics from the National Social Appeals Board The National SocialAppeals Board Copenhagen 2013 httpastdktal-og-undersogelsertal-fra-ankestyrelsen

7 Mental Illness and the Labour Market Danske Regioner Danske RegionerCopenhagen Denmark 2009 Psykisk sygdom og arbejdsmarkedet

8 Eplov LF Korsbek L Vocational rehabilitation for people with affective disordersor anxiety [Arbejdsmarkedsrettede indsatser for personer med affektive sindslidelsereller angstsygdomme] The National Labour Market Authority 2012

9 Lexis MA Jansen NW Huibers MJ van Amelsvoort LG Berkouwer A Tjin ATvan den Brandt PA Kant I Prevention of long-term sickness absence andmajor depression in high-risk employees a randomised controlled trialOccup Environ Med 2011 68400ndash407

10 Wang PS Simon GE Avorn J Azocar F Ludman EJ McCulloch J PetukhovaMZ Kessler RC Telephone screening outreach and care managementfor depressed workers and impact on clinical and work productivityoutcomes a randomized controlled trial JAMA 2007 2981401ndash1411

11 Wang PS Simon GE Kessler RC Making the business case for enhanceddepression care the National Institute of Mental Health-Harvard WorkOutcomes Research and Cost-effectiveness Study J Occup Environ Med2008 50468ndash475

12 van der Feltz-Cornelis CM Meeuwissen JA de Jong FJ Hoedeman RElfeddali I Randomised controlled trial of a psychiatric consultationmodel for treatment of common mental disorder in the occupationalhealth setting BMC Health Serv Res 2007 729

13 van der Feltz-Cornelis CM Hoedeman R de Jong FJ Meeuwissen JADrewes HW van der Laan NC Ader HJ Faster return to work afterpsychiatric consultation for sicklisted employees with common mentaldisorders compared to care as usual A randomized clinical trialNeuropsychiatr Dis Treat 2010 6375ndash385

14 Burns T Catty J Becker T Drake RE Fioritti A Knapp M Lauber C Rossler WTomov T van Busschbach J White S Wiersma D The effectiveness ofsupported employment for people with severe mental illnessa randomised controlled trial Lancet 2007 3701146ndash1152

15 Bond GR Drake RE Becker DR An update on randomized controlled trialsof evidence-based supported employment Psychiatr Rehabil J 200831280ndash290

16 Drake R Bond GR Becker DR Individual Placement and Support AnEvidence-Based Approach to Supported Employment New York OxfordUniversity Press 2012

17 Cook JA Leff HS Blyler CR Gold PB Goldberg RW Mueser KT Toprac MGMcFarlane WR Shafer MS Blankertz LE Dudek K Razzano LA Grey DDBurke-Miller J Results of a multisite randomized trial of supportedemployment interventions for individuals with severe mental illnessArch Gen Psychiatry 2005 62505ndash512

18 Gold PB Meisler N Santos AB Carnemolla MA Williams OH Keleher JRandomized trial of supported employment integrated with assertivecommunity treatment for rural adults with severe mental illnessSchizophr Bull 2006 32378ndash395

19 Hoffmann H Jackel D Glauser S Kupper Z A randomised controlledtrial of the efficacy of supported employment Acta Psychiatr Scand2012 125157ndash167

20 Killackey E Jackson HJ McGorry PD Vocational intervention in first-episodepsychosis individual placement and support v treatment as usualBr J Psychiatry 2008 193114ndash120

21 Kin WK Chiu R Tang B Mak D Liu J Chiu SN A randomized controlledtrial of a supported employment program for persons with long-termmental illness in Hong Kong Psychiatr Serv 2008 5984ndash90

22 Latimer EA Lecomte T Becker DR Drake RE Duclos I Piat M Lahaie N St-PierreMS Therrien C Xie H Generalisability of the individual placement and supportmodel of supported employment results of a Canadian randomisedcontrolled trial Br J Psychiatry 2006 18965ndash73

23 Lehman AF Goldberg R Dixon LB McNary S Postrado L Hackman AMcDonnell K Improving employment outcomes for persons with severemental illnesses Arch Gen Psychiatry 2002 59165ndash172

Hellstroumlm et al Trials 2013 14442 Page 9 of 10httpwwwtrialsjournalcomcontent141442

24 McGurk SR Mueser KT Pascaris A Cognitive training and supportedemployment for persons with severe mental illness one-year resultsfrom a randomized controlled trial Schizophr Bull 2005 31898ndash909

25 McGurk SR Mueser KT Feldman K Wolfe R Pascaris A Cognitive trainingfor supported employment 2-3 year outcomes of a randomized controlledtrial Am J Psychiatry 2007 164437ndash441

26 Tsang HW Chan A Wong A Liberman RP Vocational outcomes of anintegrated supported employment program for individuals with persistentand severe mental illness J Behav Ther Exp Psychiatry 2009 40292ndash305

27 Twamley EW Narvaez JM Becker DR Bartels SJ Jeste DV Supportedemployment for middle-aged and older people with schizophreniaAm J Psychiatr Rehabil 2008 1176ndash89

28 Campbell K Bond GR Drake RE Who benefits from supportedemployment a meta-analytic study Schizophr Bull 2011 37370ndash380

29 Bond GR Salyers MP Dincin J Drake R Becker DR Fraser VV Haines MA randomized controlled trial comparing two vocational models forpersons with severe mental illness J Consult Clin Psychol 2007 75968ndash982

30 Drake RE McHugo GJ Becker DR Anthony WA Clark RE The NewHampshire study of supported employment for people with severemental illness J Consult Clin Psychol 1996 64391ndash399

31 Drake RE McHugo GJ Bebout RR Becker DR Harris M Bond GR Quimby EA randomized clinical trial of supported employment for inner-city patientswith severe mental disorders Arch Gen Psychiatry 1999 56627ndash633

32 Mueser KT Clark RE Haines M Drake RE McHugo GJ Bond GR Essock SMBecker DR Wolfe R Swain K The Hartford study of supported employment forpersons with severe mental illness J Consult Clin Psychol 2004 72479ndash490

33 The National Labour Market Authority in Denmark The Match Model[Match model Arbejdsmarkedsstyrelsen] Copenhagen Denmark The NationalLabour Market Authority 2013 httpswwwretsinformationdkFormsR0710aspxid=139870

34 Debts counselling Settlementet The Settlement Copenhagen Denmark2013 httpsettlementet dkradgivninggaeldsradgivning

35 Denmarks active labour market policy [Lov om en aktiv beskaeligftigelsesindssats]Copenhagen Denmark Ministry of Employment 2011 httpswwwretsinformationdkFormsR0710aspxid=128679

36 Substance Abuse and Mental Health Services Administration SupportedEmployment Evaluating your Program DHHS Pub No SMA-08-4364 RockvilleMD Center for Mental Health Services Substance Abuse and Mental HealthServices Administration US Department of Health and Human Services 2009httpstoresamhsagovshincontentSMA08-4365EvaluatingYourProgram-SEpdf

37 Sheehan DV Lecrubier Y Sheehan KH Amorim P Janavs J Weiller EHergueta T Baker R Dunbar GC The Mini-International NeuropsychiatricInterview (MINI) the development and validation of a structureddiagnostic psychiatric interview for DSM-IV and ICD-10 J Clin Psychiatry1998 59(Suppl 20)22ndash33

38 The National Labour Market Authority in Denmark The DREAM databaseStatistics Denmark [DREAM databasen Danmarks Statistik] CopenhagenDenmark The National Labour Market Authority 2012 httpwwwdstdkdaTilSalgForskningsserviceDataAndre_Styrelseraspx

39 Bech P Clinical psychometrics Oxford Wiley-Blackwell 201240 OrsquoSullivan RL Fava M Agustin C Baer L Rosenbaum JF Sensitivity of the

six-item Hamilton Depression Rating Scale Acta Psychiatr Scand 199795379ndash384

41 Maier W Buller R Philipp M Heuser I The Hamilton Anxiety Scalereliability validity and sensitivity to change in anxiety and depressivedisorders J Affect Disord 1988 1461ndash68

42 Pedersen G Hagtvet KA Karterud S Generalizability studies of the GlobalAssessment of Functioning-Split version Compr Psychiatry 2007 4888ndash94

43 Pedersen G Karterud S The symptom and function dimensions of the GlobalAssessment of Functioning (GAF) scale Compr Psychiatry 2012 53292ndash298

44 Licht RW Jensen J Validation of the Bech-Rafaelsen Mania Scale usinglatent structure analysis Acta Psychiatr Scand 1997 96367ndash372

45 Morosini PL Magliano L Brambilla L Ugolini S Pioli R Developmentreliability and acceptability of a new version of the DSM-IV Social andOccupational Functioning Assessment Scale (SOFAS) to assess routinesocial functioning Acta Psychiatr Scand 2000 101323ndash329

46 Nafees B van Hanswijck de JP Stull D Pascoe K Price M Clarke ATurkington D Reliability and validity of the Personal and Social Performancescale in patients with schizophrenia Schizophr Res 2012 14071ndash76

47 Sheehan DV Harnett-Sheehan K Raj BA The measurement of disabilityInt Clin Psychopharmacol 1996 1189ndash95

48 Bech P Licht RW Stage KB Rating scales for affective disorders [Rating scalesfor affektive lidelser] Hilleroslashd Denmark Psychiatric Research Unit CCMHMental Health Center Northern Zealand 2005

49 Rogers ES Chamberlin J Ellison ML Crean T A consumer-constructed scaleto measure empowerment among users of mental health servicesPsychiatr Serv 1997 481042ndash1047

50 Miller WR Johnson WR A natural language screening measure formotivation to change Addict Behav 2008 331177ndash1182

51 Nguyen TD Attkisson CC Stegner BL Assessment of patient satisfactiondevelopment and refinement of a service evaluation questionnaireEval Program Plann 1983 6299ndash313

52 Rabin R de CF EQ-5D a measure of health status from the EuroQolGroup Ann Med 2001 33337ndash343

53 Danish Psychiatric Case Register [Psykiatrisk Centralregister] Risskov DenmarkCentre of Psychiatric research University of Aarhus 2013 httptnudkpsykiatrisk-centralregister

54 Bartko JJ Carpenter WT Jr On the methods and theory of reliabilityJ Nerv Ment Dis 1976 163307ndash317

55 Dupont WD Plummer WD Jr Power and sample size calculationsa review and computer program Control Clin Trials 1990 11116ndash128

56 Dupont WD Plummer WD Jr Power and sample size calculations forstudies involving linear regression Control Clin Trials 1998 19589ndash601

57 Burns T Catty J White S Becker T Koletsi M Fioritti A Rossler W Tomov Tvan Busschbach J Wiersma D Lauber C The impact of supportedemployment and working on clinical and social functioning results ofan international study of individual placement and supportSchizophr Bull 2009 35949ndash958

58 Howard LM Heslin M Leese M McCrone P Rice C Jarrett M Spokes THuxley P Thornicroft G Supported employment randomised controlledtrial Br J Psychiatry 2010 196404ndash411

59 van Oostrom SH van MW Terluin B de Vet HC Knol DL Anema JRA workplace intervention for sick-listed employees with distress resultsof a randomised controlled trial Occup Environ Med 2010 67596ndash602

60 Gueorguieva R Krystal JH Move over ANOVA progress in analyzingrepeated-measures data and its reflection in papers published in theArchives of General Psychiatry Arch Gen Psychiatry 2004 61310ndash317

61 The Psychiatric Central Research Register First time contacts with mentalhealth services [Foslashrstegangskontakt med det psykiatriske sygehusvaeligsen]Risskov Denmark Centre of Psychiatric research University of Aarhus 2013httptnudkpsykiatrisk-centralregisteraarstabeller

62 Burns T Catty J IPS in Europe the EQOLISE trial Psychiatr Rehabil J 200831313ndash317

63 McFarlane WR Dushay RA Deakins SM Stastny P Lukens EP Toran J Link BEmployment outcomes in family-aided assertive community treatmentAm J Orthopsychiatry 2000 70203ndash214

doi1011861745-6215-14-442Cite this article as Hellstroumlm et al The effect of IPS-modified an earlyintervention for people with mood and anxiety disorders study protocolfor a randomised clinical superiority trial Trials 2013 14442

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Hellstroumlm et al Trials 2013 14442 Page 10 of 10httpwwwtrialsjournalcomcontent141442