Journal of Affective Disorders 131 (2011) 358–363

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Journal of Affective Disorders

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Brief report

A French network of bipolar expert centres: A model to close the gapbetween evidence-based medicine and routine practice

Chantal Henry a,b,c,d,⁎, Bruno Etain a,c,d, Flavie Mathieu a, Aurélie Raust c,d,Jean-Francois Vibert e,f,g, Jan Scott h,i, Marion Leboyer a,b,c,d

a INSERM, U 995, IMRB, Psychiatry Genetics, Creteil, Franceb University Paris 12, Faculty of Medicine, IFR10, Creteil, Francec AP-HP, Henri Mondor-Albert Chenevier Hospitals, Department of Psychiatry, Creteil, Franced Fondation FondaMental, Francee INSERM, UMR S 707: Epidemiology, Information Systems, Modelisation, Paris, Francef UPMC University Paris 06, UMR S 707, Paris, F-75012, Franceg AP-HP, Hôpital Saint Antoine, Service de Physiologie, Paris, Franceh Institute of Neuroscience, Newcastle University, UK and Visiting Professor, University Paris 12, Creteil, Francei University Paris 12, Creteil, France

a r t i c l e i n f o

⁎ Corresponding author. Pôle de psychiatrie du CHChenevier, 40 rue de Mesly, 94000 Créteil, France. Telfax: +33 1 49 81 30 99.

E-mail address: chantal.henry@inserm.fr (C. Henry

0165-0327/$ – see front matter © 2010 Elsevier B.V.doi:10.1016/j.jad.2010.11.013

a b s t r a c t

Article history:Received 10 September 2010Received in revised form 10 November 2010Accepted 11 November 2010Available online 7 December 2010

Background: Bipolar disorders are a major public health concern. Efforts to provide optimalcare by general practitioners and psychiatrists are undermined by the complexity of thedisorder and difficulties in applying clinical practice guidelines and new research findings tothe spectrum of cases seen in day to day practice.Method: A national network of bipolar expert centres was established. Each centre hasestablished strong links to local health services and provides support to clinicians in deliveringpersonalized care plans derived from systematic case assessments undertaken at the centre.Results: A common set of diagnostic and clinical assessment tools has been adopted at eightcentres. Evaluations are undertaken by trained assessors and cross-centre reliability ismonitored. A web application, e-bipolar© is used to record data in a common computerizedmedical file. Anonymized data is entered into a shared national database for use inmulti-centreaudit and research.Conclusions: Instead of offering treatment advice based on clinical practice guidelinesrecommendations for selected sub-populations of patients (a ‘top-down’ approach), theFrench bipolar network offers systematic, comprehensive, longitudinal, and multi-dimensionalassessments of cases representative of general bipolar populations. This ‘bottom-up’ strategymay offer a more efficient and effective way to transfer knowledge and share expertise as thereferrer can appreciate the rationale underpinning suggested treatment protocols and morereadily apply such principles and approaches to other cases. The network also builds aninfrastructure for clinical cohort and comparative-effectiveness research on more represen-tative patient populations.

© 2010 Elsevier B.V. All rights reserved.

Keywords:Bipolar disordersExpert centreClinical practice networkTreatment guidelineTranslational research

U Créteil, Hôpital A..: +33 1 49 81 32 31;

).

All rights reserved.

1. Introduction

Despite their high prevalence, bipolar disorders are oftenunrecognized or mis-diagnosed leading to delayed treat-ments (Baca-Garcia et al., 2007). However, even when thediagnosis is established, it is clear that the management of BPis a major challenge and surveys confirm that both under-use

359C. Henry et al. / Journal of Affective Disorders 131 (2011) 358–363

of guidelines and sub-optimal treatment are common con-cerns in Europe and the USA (Merikangas et al., 2007; Scottet al., 2006).

In many countries, increased knowledge and expertise inthe management of BP have come about through thedevelopment of academic centres that undertake research onthe disorder and also offer a clinical ‘tertiary’ referral service—usually a specialist clinic targeted at treatment-refractory cases.However, the impact of such centres on the overall effective-ness of local mental health services is questionable. Also, theclinical operational policies of the specialist clinics evolvedindependently of each other and there have rarely been anycoordinated cross-centre strategies.

Even when research assessments are undertaken on awider range of clinical sub-groups, the complete evaluation israrely shared with local clinicians and the expert advice onclinical referrals, like treatment guidelines, are usually heavilyweighted towards communicating the therapeutic options(a top-down approach), rather than a detailed explanation ofthe assessment processes and findings (a ‘bottom-up’approach). Thus an opportunity is missed to reinforce howthe comprehensive individualized assessment, which is nowa cornerstone of research into phenotypes, biomarkersand predictors, also represents a ‘personalized medicine’approach to BP. As such, the current modus operandi of manyBP expert centres, although necessary for academic excel-lence, is not sufficient for closing the research efficacy-clinicaleffectiveness gap.

In France, the need to improve diagnosis and treatment ofBP led both the Ministry of Research and the Ministry ofHealth to support the development of a national networkof BP expert centres under the aegis of ‘FondaMental’(a scientific foundation created in 2007). This paper describeshow the foundation used this opportunity to introduce a newmodel for clinical collaboration between expert centresand local clinicians (general practitioners and generalpsychiatrists) who provide the first point of contact withhealth services for most individuals with BP. The centres offerwide access for all BP cases with few barriers for referral andno biases towards treatment-refractory cases. There is anemphasis on providing reliable systematic multi-dimensionalassessments of cases whether or not they are recruited toresearch projects, and also on sharing the findings ofassessments alongside any treatment recommendationswith referring clinicians. The aim is to establish the expertcentres as a valued additional and accessible local service forindividuals with BP and their treating clinicians. The long-term goal, in keeping with the ideas outlined by Insel (2009),is to integrate academic and clinical practice to reduce the gapbetween research knowledge and public health impact inpsychiatry.

The following sections outline the rationale and selectioncriteria for the centres and include discussions of keyelements of the assessment process.

2. Centre development

2.1. Rationale

The network of expert centres is envisioned as aninnovative health care system that will support rather than

replace the existing health system. The BP expert centres arerequired to first provide a comprehensive systematic assess-ment of patients with a probable diagnosis of BP, and then toelaborate diagnostic issues, give advice on potential treat-ment pathways, andmonitor progress systematically throughfollow-up reviews. This integrated approach aims to:

• accelerate access to specialists for all BP cases (and ‘highrisk’ probands)

• reduce delays between illness onset, accurate diagnosis andintroduction of appropriate treatment

• enhance concordance between evidence-based medicineguidelines and clinical practice

• disseminate knowledge and skills about new therapeuticstrategies

• promote a personalized medicine approach by

� investigating the underlying pathophysiology of BP andits sub-types

� improving detection and prevention of comorbid somaticand psychiatric disorders

� prospectively evaluating the impact of treatments recom-mended for the individual and establishing protectiveand risk factors for relapse.

2.2. Site selection

Sites must be affiliated to an academic centre activelyinvolved in BP research and have the will to integrate thenetwork.

2.3. Working groups and training

A multidisciplinary team of clinical representatives fromFondaMental formed a working group to select the instru-ments for the clinical assessment. Valid and reliable observerand self-rating scales were prioritized and all those involvedin patient assessments receive training in the use of measuresthey employed.

3. Centre activity

Eight expert centres have opened so far across France.Clinical team members from each centre have regular jointmeetings to ensure inter-rater reliability, receive or providetraining in new therapeutic interventions, initiating newresearch studies, as well as discussing with advocacy groups arange of anti-stigma campaigns.

Beyond the support provided for managing patients,clinical training initiatives have been introduced, and psy-chologists and psychiatrists involved in the network havetrained other colleagues in the use of interventions such asFondaMental Campus, a psychoeducation program for BP.

3.1. Referral criteria and eligibility for assessment

Patients assessed in expert centres have been referred by ageneral practitioner or psychiatrist, who afterwards receive adetailed evaluation report along with suggestions for thera-peutic interventions. Although patients are reviewed at theexpert centre, routine care and treatment is still undertakenby the treating physician (i.e. the referrer).

360 C. Henry et al. / Journal of Affective Disorders 131 (2011) 358–363

The goal is to provide a more ‘personalized medicine’approach to general populations of BP patients. Comprehen-sive assessment is offered at the earliest possible time in anindividual's BP career to try to prevent adverse outcomes andthe negative consequences of poorly controlled episodes. Inaddition, the research arm of the expert centres is seekingout ‘high risk’ probands to investigate and develop earlyintervention strategies. Exclusion criteria for referral areminimal, and all patients who purportedly meet diagnosticcriteria for any BP sub-type (I, II, or Not Otherwise Specified)can be assessed. However, those referred during a moodepisode do not complete the full evaluation immediately;some assessments are delayed until the patient no longermeets the criteria for a current episode and/or is able toparticipate in the procedure.

3.2. Data collection: electronic healthcare record system andnational database

A web-based application, e-bipolar© was developed tocollate assessment data for clinical monitoring and researchpurposes. Access to the system is carefully regulated andapproval was obtained from the ethical committee and thecommittee in charge of the safety of computerized databases(CNIL). To optimize data entry and retrieval, free text input hasbeen minimized, and drop down lists and other approachesleading to standardized inputs chosen when possible. The XMLformat is used to transfer data from e-bipolar© into ananonymous national database.

3.3. Assessment procedure and report

3.3.1. Pre-screeningBefore participating in the full assessment, patients are

interviewed by a psychiatrist at the expert centre who:

– confirms the diagnosis of BP meeting DSM-IV criteria(American Psychiatric Association, 1994) and assesses theneed to perform the full evaluation.

– informs the patient of the formal assessment procedureand schedules the appointments.

Patients with BP who consent to participate in theassessment protocol (and who were not currently in a fullBP episode) are then invited to complete the assessmentprocedure over a period of about 2 days.

3.3.2. Standardized assessment packageThe same package of evaluations has been adopted by all

centres and the full assessment is performed by members of aspecialized multidisciplinary team: a nurse, a clinical psy-chologist, a neuro-psychologist, a psychiatrist and a socialworker (as appropriate). Table 1 provides a list of the self andobserver-rated measures included (a description of theinstruments selected can be provided).

This is a wide-ranging psycho-bio-social assessment thatsystematically explores all potential aspects of the presenta-tion and factors that influence course and outcome. Themeasures are relevant for research as well as providingstructured evaluations for clinical purpose.

3.3.3. Follow-up assessmentsEvery 6 months (for 3 years), the patient is re-evaluated to

prospectively record any significant changes that haveoccurred including clinical progress but also periods ofhospitalization and/or medical sick leave. Mood states,residual symptoms, suicide attempts and ideation, socialfunctioning, resource utilization, treatments (including sideeffects and adherence), sleep quality and vigilance aremonitored.

The majority of clinical measures in the initial assessmentare repeated annually (including sections of the SCIDinterview to examine changes in diagnosis and comorbiditiesand evaluation of inter-episodic functioning) and then at yeartwo the neuro-cognitive battery is also repeated.

3.3.4. Clinical reportAt the end of each evaluation, a personalized treatment

program is proposed taking into account the informationderived from the clinical assessments and medical work up.Importantly, management strategies can be revised not onlyaccording to changes in individual patient needs but also inkeeping with updates to recommended treatment algorithmsbased on empirical research findings.

The individual treatment plan is usually multifaceted andmay include information on the rationale for the selection of aparticular mood stabilizer based on a detailed risk–benefitassessment, plus options for using a combination of relapseprevention and health improvement strategies such as grouppsychoeducation and improvement in the individuals' diet.The programmay also offer the opportunity for patients to beinvolved in novel approaches being trialled at the expertcentres (and not routinely available elsewhere) such ascognitive remediation therapy.

3.4. Research: scientific issues

The electronic healthcare record system for each expertcentre is connected to a national database and data on thislarge clinically representative cohort of BP cases will allowprospective follow-up and comparative-effectiveness studies.

Moreover, patients might also be included in specificresearch programs based on collaborations between expertcentres and several teams involved in genetics, biomarkers,brain-imaging research. These programs will take advantageof the extensive clinical assessment that will be used as acomprehensive phenotype.

4. Discussion

There is an international agreement that greater supportand advice are needed to help clinicians to improve evidence-based management of BP.

One strategy for translating research knowledge intohealth improvements has been the introduction of clinicalpractice guidelines. Whilst adherence to treatment guidelineshas been shown to improve clinical outcomes (Bauer et al.,2009), there are a number of challenges in using these as avehicle for improving the general clinical management of BP.Many clinicians (especially those working independently inprivate outpatient clinics) are not familiar with existingguidelines, whilst others suggest that internationally-agreed

Table 1Overview of the initial assessment package employed by the French bipolar network of expert centres.

Assessment Measures employed

Pre-screeningBP diagnostic screen DSM-IV criteriaCurrent symptomatology

Manic symptoms Altman Mania Rating Scale (AMRS) (Altman et al., 1997)Depressive symptoms Inventory of Depressive Symptoms-Self-Rating version (IDS-SR 16) (Corruble et al., 1999)

Current treatment e-bipolar© checklist organized by drugs classes

1st evaluationSocio-demographic data e-bipolar© questionnaireBipolar diagnostic interview Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID) (First, 1996)Bipolar lifetime characterization SCID

e-bipolar© questionnaire (past year review)Current mood states and residual symptoms

Depressive Montgomery and Asberg (MADRS), IDS-SR16, DSM-IV criteria (Montgomery and Asberg, 1979) (APA, 1994)Manic Young Mania Rating Scale (YMRS), AMRS, DSM-IV criteria (Young et al., 1978)Anxiety Spielberger Anxiety Scale (STAY-A) (Spielberger, 1983)Multi-dimensional assessment of moods Multi-dimensional Assessment of Thymic States (MATHYS) (Henry et al., 2008)

Functioning and severity of disorderGlobal functioning Global Assessment of Functioning scale (GAF)Social functioning Functioning Assessment Short Test (FAST) (Rosa et al., 2007)Severity of the illness Clinical Global Impressions Scale (CGI)

Psychiatric comorbidities and traumaCurrent and past SCIDPast history of ADHD Wender Utah Rating Scale (WURS) (Ward et al., 1993)Past history of trauma Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 1994)

Suicidal behaviourPersonal history of suicide attempts Suicide Intent Scale (SIS) (Beck et al., 1974)Characterizationofmostviolentand lethal attempt Risk Rescue Rating Scale (Weisman and Worden, 1972)Assessment of suicidal feelings Measure of suicidal Ideation (ISF) (Paykel et al., 1974)

Medical burden and risk factorsMedical comorbidity e-bipolar© (checklist adapted from Pittsburgh medical inventory)Lifestyle Fagestrom questionnaire (Heatherton et al., 1991) SCIDSmoker status/nicotine dependenceAlcohol and substance misuse

Physical examination Weight, height, BMI, blood pressure, waist measurement; ECGBiochemistry screen Liver, thyroid and renal functions; lipids, blood glucose; full blood count; CRP, serum levels of mood stabilizers

Sleep disturbanceQuality of sleep Pittsburgh Sleep Quality Index (PSQI) (Buysse et al., 1989)Vigilance scale Epworth Vigilance Scale (Johns, 1991)

TreatmentPharmacological e-bipolar© checklist organized by drug classes (adapted from the Theriaque list)Current and past psychotropic agentsand/or somatic treatmentAdherence Medication Adherence Rating Scale (MARS) and serum level of mood disorders (Misdrahi et al., 2004)Side effects Prise-M

Psychosocial Interventions e-bipolar© checklist (CBT, Psychoeducation, IPSRT, etc.)Inter-episode assessment

Emotional reactivity Affect Intensity Measure (AIM), Affective Lability Scale (ALS) (Larsen et al., 1986) (Harvey et al., 1989)Impulsivity/hostility Barrat Impulsiveness Scale version 10 (BIS-10)/Buss and Durkee Hostility Inventory (BDHI)

(Patton et al., 1995) (Buss and Durkee, 1957)Chronotype Composite Scale of Morningness (CSM), circadian type inventory (Smith et al., 1993)

Family historyPsychiatric comorbidities and suicide behaviour e-bipolar© checklist for 1st degree relatives (mood disorders, schizophrenia, alcohol and substance misuse,

suicide and suicide attempts, and dementia)Risk factors for metabolic syndrome History in 1st degree relatives of diabetes, hypertension, obesity and dyslipidaemia

Cognitive functioningPremorbid IQ and current level WAIS-III (Vocabulary and Matrix reasoning)Verbal episodic memory California Verbal Learning Test (CVLT)Working memory WAIS-III (Digit Span)Processing speed WAIS-III (Digit Symbol Substitution and Symbol Search)Attention CPT IIExecutive functions Verbal Fluency, Stroop, Trail-Making (A and B) Tests

361C. Henry et al. / Journal of Affective Disorders 131 (2011) 358–363

treatment protocols are not well-adapted to routine practiceas they do not take into account the needs of an individualpatient in their complexity. Moreover, guidelines cannotsufficiently take into account the socio-cultural, health careresourcing, or organizational issues, etc.

Guidelines are often viewed as ‘top-down’ measuresbecause the aim is to bring about changes in clinical behaviourthrough adherence to treatment protocols without support forclinicians to adopt this approach or adequate explanation ofhow the conclusions were reached (Quaglini, 2008; Scott et al.,

362 C. Henry et al. / Journal of Affective Disorders 131 (2011) 358–363

2002). Furthermore, research advances often mean thattreatment guidelines are rapidly out-dated as they aresupersededbynewtreatment recommendations. This indicatesthat treatment guidelines alone are insufficient to translateresearch findings into day to day clinical practice. There is anincreasing need to target knowledge and skills in assessment(a bottom-up approach) so that clinicians canmore confidentlyidentify the best combination of interventions currentlyavailable for an individual patient, whilst in the long-term itwill improve familiarity with ‘personalized medicine’ models.

Re-organization of health care systems to meet the multi-dimensional needs of individuals with BP is not viable in manycountries. However, in France an opportunity arose tosimultaneously establish several expert centres and a strategicdecision was made to devise a shared philosophy of clinicalpractice whilst developing the infrastructure for multi-siteresearch. Consistency of approach is achieved by the eightcentres jointly adopting the same detailed assessment proce-dures, which are used routinely for clinical and research cases.

Similar approaches may be impossible to set up incountries with different health systems but other alternativestrategies can be proposed such as for example collaborativecare as described by Bauer et al. (2009).

In terms of clinical research, the French network willprovide follow-up data of interest of samples representativeof general BP populations. The FondaMental network isdeveloping a series of prospective clinical cohort studieswhich build on, but offer a more extensive range of systematicassessments, to those undertaken by the Systematic TreatmentEnhancement Program for Bipolar Disorder (STEP-BD) and theStanley Foundation Bipolar treatment outcomenetwork (Sachset al., 2003; Post et al., 2001). Also, the French network hasestablished strong links with several basic research teams toallow investigation of underlying disease mechanisms. Theclinical assessments being undertaken can therefore be used todevelop a comprehensive picture of phenotypes for a range offuture basic science studies.

At the European level, FondaMental is leading the ENBRECproject (European Network of Bipolar Research Centres;funded by an FP7 grant) (www.enbrec.eu), which underpinsthe development of multi-site work across BP expert centresin several countries, whilst within France, FondaMental isnow extending this expert centre model for other psychiatricdisorders, namely schizophrenia and autism.

Role of funding sourceFunding for the construction of the network was provided by the French

Ministry of Research (RTRS Santé Mentale) and attributed to the FrenchNational Science Foundation FondaMental (Journal official de la Républiquefrançaise, 17 juin 2007). This research was supported by grants from InstitutNational de la Santé et de la Recherche Médicale (INSERM).

Conflict of interestThe authors have no actual or potential conflict of interest including

financial, personal or other relationships with other people or organizationswithin three years of beginning the work submitted that could inappropri-ately influence, or be perceived to influence, this work.

Acknowledgments

We thank Arnaud Henry who developed e-bipolar© andMichael Berk for his helpful comments.

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