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Seventh Framework Programme - Health

European Comparative Effectiveness Research on Internet-based Depression Treatment

Grant Agreement no. 603098-2

Project acronym E-COMPARED

Project title European Comparative Effectiveness Research on Internet-based Depression Treatment

Funding scheme Collaborative project

Date of Annex 1 4th of April 2014

Periodic report no. 1st

Period covered From 1st of January 2014 to 30th of June 2015

Representative of project’s coordinator

Heleen Riper, Ph.D.

Professor eMental-Health/ clinical psychology

VU University Amsterdam

Tel. +31 205988759

Fax.

E-mail [email protected]

Project’s website http://www.E-COMPARED.eu

Grant Agreement No: 603098-2 E-COMPARED

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1. Publishable summary 3 2. Core of the project 5 2.1. Project objectives for the period 5 General aim and approach 5 Work package structure 6 Planning -‐ Gantt chart 7 WP1: Adult depression treatment in primary and routine specialized mental care services 7 WP2: Comparing the clinical and cost-‐effectiveness of internet-‐based treatment and TAU 7 WP3: Economic modelling studies 8 WP4: Personalised Depression treatment modelling 8 WP5: Synthesis of results, EU recommendations and business case development 8 WP6: Dissemination 9

2.2. Work progress and achievements during the period 9 WP1: Adult depression treatment in primary and routine specialized mental care services 10 WP2: Comparing the clinical and cost-‐effectiveness of internet-‐based treatment and TAU 12 WP3: Economic modelling studies 18 WP4: Personalised Depression treatment modelling 21 WP5: Synthesis of results, EU recommendations and business case development 24 WP6: Dissemination 27

2.3. Project Management 28 Management Structure 29 Scientific Advisory Board 31 Communication Tools and Procedures 31 Contracts and binding documents 32 Reporting 32 Project meetings 32 Cooperation with other projects 34 Financial management 34 Changes in the consortium 35 Changes to the legal status of the beneficiaries 35 Project planning and status 35 Problems occurred and envisaged solutions 35

3. Deliverables and milestones 37 4. Use of resources 39 4.1. Overview per partner 40 RTD – Research (WP1-‐WP5) 40 OTH -‐ Dissemination (WP6) 40 MGT – Project Management (WP7) 41

4.2. Overview per work package 42 4.3. Specific costs for subcontracted services 42 4.4. Receipts received from third parties 43 4.5. Deviations from budget 43

Annex 1: Detailed Gantt Chart 45 Annex 2: Dissemination activities 47 National Dissemination Activities 47 International Talks and Poster Presentations 50 Scientific publications 50

Annex 3: Trial Registers E-‐COMPARED studies 51


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1. Publishable summary E-COMPARED aims to provide mental healthcare stakeholders with evidence based information and recommendations about the clinical and cost-effectiveness of blended depression treatment.

To this end, current mental health policies and guidelines in Europe for both treatment-as-usual (TAU) and internet-based treatment for depression are compared and evaluated.

Furthermore, E-COMPARED engages in eight comparative effectiveness trials to evaluate the clinical and cost-effectiveness of blended internet-based depression treatment as compared to TAU in routine primary healthcare and specialized mental health service centres. Blended treatment entails a combination of Internet, mobile-based, and face-to-face interventions. The randomised controlled trials are conducted in the United Kingdom, Poland, Spain, Germany, Switzerland, Sweden, France and The Netherlands.

The evidence generated by these trials will enable the consortium to provide a macro-economic model that allows for calculating different scenarios, costs and levels of internet-based depression treatment implementation throughout Europe.

Artificial intelligence and advanced machine learning techniques will be employed to predict which patient groups could benefit from internet-based treatment versus treatment as usual by modelling individual patient characteristics.

E-COMPARED will result in evidence-based recommendations for policy and decision makers to inform to what extent blended internet-based depression treatment is opportune to integrate in routine primary healthcare and outpatient specialized practices for depression treatment in the European Union.

The first eighteen months of the three-year project focussed on reviewing the current practice in internet-based treatment for depression in Europe. This included an extensive stakeholder survey, systematic review and individual patient data meta analysis. Our study concluded that there is a marked difference in availability and support for internet-based therapy throughout Europe, associated to between-country differences in terms of e-health implementation and associated preconditions such as reimbursement policies.

Mental health care stakeholders’ knowledge of Internet treatment varies, but potential benefits of internet-based treatment such as increased capacity in mental health care system are readily identified. Blended therapy (blending face-to-face and internet therapy) was viewed more favourable compared to stand-alone Internet-based therapy. A majority of stakeholders indicates that their organization would/did recommend blended therapy for mild (70.5%) and moderate depression (58.4%) respectively. Although the current number of studies is low, our systematic review and Individual Patient Data Meta-Analysis (IPDMA) showed up until now that blended treatment do provide promising results in terms of clinical effectiveness. They also show that that is a gap regarding clear descriptions on what the blended treatments exactly entail in terms of face to face versus online components. Regarding the current state of depression care in Europe, we can conclude that gaps exist between current practice and distributed care. The report is available on request.

A second focal point in the work so far has been the preparations for the eight comparative effectiveness trials in the UK, France, Poland, the Netherlands, Spain, Germany, Switzerland and Sweden. The study protocol, treatment protocols and data management infrastructure have been developed and approved by competent ethical


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and regulatory authorities. Another major achievement is the acceptance by the clinical partners of the various technical treatment platforms used to offer the blended internet-based treatment. The treatment platforms include amongst others client and therapists portals, mobile components and ecological momentary assessment (EMA) techniques. Real patients in real care settings are receiving treatment. Noteworthy is that the ICT4Depression/Moodbuster platform for which the development has started in the FP7 funded ICT4Depression project (GA 248778), now is refined in the context of E-COMPARED and active in five EU mental healthcare settings: PL, UK, FR, DE and NL.

Besides preparing the generic Markov model for depressive disorder, the cost-effectiveness analyses and modelling focussed on the possibility to also include the Discrete Event Simulation (DES) technique for reasons of comparability and innovating methods for cost-effectiveness research.

Furthermore, the E-COMPARED team developed a virtual patient model including the technical infrastructure, which are currently used to simulate data for developing and testing the personalised treatment modelling. Once the data from the clinical effectiveness studies are collected, the models will be validated in their capacity of estimating the most appropriate treatment option for specific groups of patients.

To prepare for synthesising the results from the comparative effectiveness studies and patient modelling, the consortium defined a first set of key outcome variables, which are related to relevant stakeholders of the E-COMPARED project. This will enable to develop a route map to the future development of guidelines and recommendations that caters for specificities of the stakeholders involved.

To disseminate the projects findings, the E-COMPARED consortium developed a detailed dissemination plan that includes both national oriented and international tailored dissemination activities. Up until now, various elements of the E-COMPARED project have been presented and discussed at over 40 national events and meetings, 4 international events and in 4 scientific publications. This resulted amongst others in new initiatives, and close collaboration with the MasterMind project (mastermind-project.eu) and initiated a comparative effectives trial in Demark that is liaised to the E-COMPARED project.

The E-COMPARED project aims to contribute to improve European mental health care by enabling policy and decision makers to make informed decisions regarding the implementation of interventions that are both clinically effective and cost-effective. This will benefit patient outcomes, quality of life and social costs lost to one of the largest contributors to disease and disability in Europe: depression.

Please refer to our website (e-compared.eu) for more information on the project’s objectives, approach, partners and results, or contact us directly at [email protected] or [email protected]


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2. Core of the project

2.1. Project objectives for the period

General aim and approach E-COMPARED aims to provide mental healthcare stakeholders with evidence based information and recommendations about the clinical and cost-effectiveness of blended depression treatment. To achieve this, the E-COMPARED consortium pursues the following objectives: - To compare and evaluate current mental health policies and guidelines in Europe for

both treatment-as-usual (TAU) and internet-based treatment for depression. - To synthesize current knowledge about the clinical and cost-effectiveness of internet-

based depression treatment, as compared in controlled settings to treatment as usual. - To evaluate the clinical and cost-effectiveness of internet-based depression treatment

as compared to TAU in routine primary healthcare and specialized mental health service centres.

- To predict which patient groups could benefit from internet-based treatment versus treatment as usual by intelligent modelling of individual patient characteristics.

- To provide a macro-economic model that allows for calculating different scenarios, costs and levels of internet-based depression treatment implementation throughout Europe.

- To provide evidence-based recommendations and informing how internet-based depression treatment can be integrated into routine primary healthcare and outpatient specialized practices for depression treatment in the European Union.

For E-COMPARED, eight pragmatic Randomized Controlled Trials on the treatment of depression are conducted in different countries and different care settings in the United Kingdom, Poland, Spain, Germany, Switzerland, Sweden, France and The Netherlands.

Each trial consists of a blended treatment condition and a treatment-as-usual (TAU) condition. Blended treatment entails a combination of Internet, mobile-based, and face-to-face interventions. For the blended intervention, an Internet based platform will be employed of similar Cognitive Behavioural Treatment (CBT) and monitoring components as in treatment-as-usual. Besides the internet-based therapy, the ICT platforms contain: - A mobile phone component, presenting CBT therapies to the patient and enabling

daily monitoring of the state of the patient; - An intelligent reasoning system that provides automated tailored feedback to patients

and professionals on the basis of patient progress; - The ability to collect data through Ecological Momentary Assessment.

Existing internet-based treatment platforms are adapted to the specific needs of the participating countries and the trial requirements. The following platforms are used: - ICT4Depression/Moodbuster is developed and evaluated in the FP7 funded project:

ICT4Depression. This platform is used by 5.InGeest/1.VUA (NL), 15.INSERM (FR), 11.SWPS (PL), 3.FAU (DE) and 4.LSHTM (UK).

- Smiling is Fun is developed and evaluated in the FP7 project OPTIMI, and is used by 6.UJI and 10.UVEG in Spain.

- Iterapy is developed and used by 2.LiU, Sweden. - Deprexis Is developed by GAIA and is used by 9.UBERN Switzerland.


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Participants are recruited from routine mental healthcare settings. Inclusion criteria include, informed consent, aged between 18 and 65 years, and have a diagnosed major depressive disorder according to the DSM-IV.

The central assumption (hypothesis) investigated in each trial is that both forms of treatment will lead to similar clinical improvements in patients (non-inferior), but that the blended form can be offered at significantly lower costs.

Work package structure The project is structured into seven highly interactive Work Packages (WPs) (see figure 1). WP1 provided an overview of the current state of Internet-based treatment for depression and TAU in routine practices from the perspectives of mental health policy and services organisations, reimbursement, clinical effectiveness and guidelines, cost-effectiveness and advantages and barriers for implementation. These results provide the fine-tuning of the start of WP2 (conduct of randomized controlled trials in routine practices). It also synthesizes the natural course of depression, which provides the necessary input the economic (WP3) and individual patient modelling (WP4). WP2 delivers in turn in addition to cost-effectiveness data on the basis of the trials also input for the modelling activities of WP3 and WP4 on an aggregated level. WP4 delivers data on subgroups of patient populations namely those who benefit in clinical terms of Internet-based treatment for depression and TAU. These will be used in the economic modelling of WP3, which enables to provide additional cost effect estimates that reflect the effects in these specific populations. WP5 synthesizes the results of WP1-WP4 and translates these to the needs of the relevant stakeholders in terms of recommendations, guidelines including a business case for future implementation. WP6 is focused on the exploitation & dissemination of the E-COMPARED results. WP7 contains the project management roles.

Figure 1: WP structure and flow


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Planning - Gantt chart The Gantt Charts below show the detailed timeline of the project per year including all the relevant deadlines for internal and official deliverables. The complete tables of deliverables with corresponding responsible partner and deadline are included in section 3. A detailed Gantt chart on task level is included in annex 1.

Figure 2: Gantt chart

The following sections describe the Work Package specific objectives. Objectives presented in grey were not active in reporting period 1.

WP1: Adult depression treatment in primary and routine specialized mental care services Main objective: to assess the current state of depression treatment policies, practices and clinical guidelines for the treatment of depression in routine primary and specialised care setting across a subset of eight EU countries.

Specific objectives: - To consult and discuss the current state of the art of depression treatment with national

and European stakeholders, including representatives of patient organisations of depression

- To assess patients’ needs and preferences for internet-based treatments for depression - To present and consult on the objectives with these stakeholders - To explore what is known about current advantages, disadvantages and harm on

internet-based treatments compared to TAU and how these may be overcome - To investigate what the reasons are for participating countries to invest in blended

internet-based treatments for depression in primary and specialised mental care services formats from the perspective of relevant stakeholders

- To explore the future plans on internet-based treatments across a number of European networks

WP2: Comparing the clinical and cost-effectiveness of internet-based treatment and TAU Main objective: to assess the feasibility and compare the clinical and cost effectiveness of internet-based ‘blended’ depression treatment for adults with MDD in routine primary and specialised care practices compared with Treatment as Usual (TAU).

Specific objectives: - Adapt the existing internet-based treatment platforms to the specific needs of the

participating countries and trial requirements - Enable the daily monitoring of the depression state of patients by mobile phone

applications for use by all trial partners


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- To develop interfaces that allow communication between the various technical components of platforms that are part of the interventions tested in the trials

- To develop a common technical infrastructure to gather, share and analyse data which can be easily used to integrate analysis across all research sites

WP3: Economic modelling studies Main objective: to estimate the cost-effectiveness of implementation of internet-based ‘blended’ depression treatment in primary care and specialized care with a five-year time horizon in comparison with TAU.

Specific objectives: - To build a generic Markov model to simulate the natural course of depression - To populate the Markov mode with cost and effect estimates of internet-based

blended depression treatment and TAU in both primary care and specialized care settings and to assess the cost-effectiveness and budget-impact of the implementation of web-based ‘blended’ depression treatment in comparison with TAU from different perspectives using different scenarios.

- To show the feasibility and generic applicability of using the model to assess the cost-effectiveness of implementation of web-based ‘blended’ depression treatment in comparison with TAU for countries that do not participate in the trials in WP2

- Countries’ RCT pooled results will be used to generate country specific cost-effectiveness estimates.

WP4: Personalised Depression treatment modelling Main objective: to provide an innovative computerized method that contributes to the assessment of the impact of internet-based blended treatments compared to TAU on an individual patient level.

Specific objectives: - Development of dynamic models based on the state-of-the-art in depression treatment

as collected in WP1 - Development of a distributed infrastructure to improve models based on data that will

be collected in WP2 - Application of machine learning techniques for improvement of predictive models - Identification of patient clusters to assess the effectiveness of treatment types

WP5: Synthesis of results, EU recommendations and business case development Main objective: To formulate a series of evidence-based recommendations and policy guidelines for relevant stakeholders on how internet-based treatments for depression can be implemented cost-effectively into routine primary care and specialised mental care services for adults.

Specific objectives: - To synthesize current evidence about depression and treatment impact (WP1), new

evidence emerging from the pragmatic clinical trials (WP2), and results of the studies on cost-effectiveness (WP3), individual patient modelling and simulation (WP4)

- To translate the results of E-COMPARED to the needs of the relevant stakeholders (WP1) and provide subsequently recommendations and policy guidelines on how internet-based treatments for depression in routine clinical primary and specialized care can be implemented in a cost-effective way

- To develop a business case for the implementation of eMental healthcare within Europe


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WP6: Dissemination Main objective: to disseminate the project results to all relevant stakeholders and to maximize its exploitation potential.

Specific objectives: - To define an integrated strategy for E-COMPARED dissemination activities - To regularly inform all stakeholders about the project and progress - To offer a platform for continuous exchange of information with all stakeholders

2.2. Work progress and achievements during the period In general, the work has progressed as planned, no abnormalities in resource allocation occurred, and various minor and major achievements can be accounted for.

One important achievement for the E-COMPARED project is the delivery of D1.1, a European overview of the current state of treatment as usual of adult depression treatment (TAU) in routine practice; Internet based treatment for depression and blended treatment of depression (bCBT). This deliverable is the result of WP1 and concluded that there is a marked difference in availability and support for internet-based therapy throughout Europe, associated to between-country differences in terms of e-health implementation and associated preconditions such as reimbursement policies. Mental health care stakeholders’ knowledge of Internet treatment varies, but potential benefits of internet-based treatment such as increased capacity in mental health care system are readily identified. Blended therapy (blending face-to-face and internet therapy) was viewed more favourable compared to stand-alone Internet-based therapy. A majority of stakeholders indicates that their organization would/did recommend blended therapy for mild (70.5%) and moderate depression (58.4%) respectively. Although the current number of participants in the study is low, our systematic review and IPDMA showed up until now that blended treatment do provide promising results in terms of clinical effectiveness. They also show that there is a gap regarding clear descriptions on what the blended treatments exactly entail in terms of face to face versus online components. Regarding the current state of depression care in Europe, we can conclude that this gaps between current practice and distributed care exists.

For WP2, a great deal of work has been put in the development of the study protocol, the adaptation, testing and refinement of the technical treatment platforms, and the preparations of the trials including obtaining the ethical approvals. The WP2 team made it possible to conduct a high quality comparative effectiveness study in eight different healthcare systems in Europe to test innovative blended treatment for depression. The fact that the technical platforms, a database and data management system, and the study protocol are delivered as planned (see Deliverable D2.2 and D2.3) and accepted by all trial partners as planned for, is a major achievement. The treatment platforms including mobile components and ecological momentary assessment (EMA) techniques are life and patients are currently receiving treatment in 8 different countries. Noteworthy is also that the ICT4Depression/Moodbuster platform for which the development has started in the FP7 funded ICT4Depression project (GA 248778), now is employed and used in five EU mental healthcare settings: PL, UK, FR, DE and NL. The inclusion of France as an additional trial partner, obtaining ethical approval for the Dutch trial and the embedding of the trial in the UK site, took more time and effort than anticipated and has led to a delay of inclusion of patients for the French, Dutch and UK trial sites.

The work for WP3 began with discussing and including a second economic modelling technique (Discrete Event Simulation, DES) to the work plan for reasons of comparability and innovating methods for cost-effectiveness research. Due to extending the work for


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WP3 with also delivering a generic DES model and comparing the performances of both Markov and DES modelling for eMental health in Europe, an inevitable delay occurred in developing the generic model. This however has no influence on the work in other Work Packages and is meant to enrich the output in terms of cost-effectives estimates of offering patients a blended treatment versus treatment currently offered in routine practice.

WP4 is running according to plans and a virtual patient model and the technical infrastructure are developed and currently used to simulate data for developing and testing the personalised treatment modelling. Once the data from the clinical effectiveness studies in WP2 is ready for analyses, the work in WP4 will populate and refine the personalised models for estimating the most appropriate treatment option for specific groups of patients.

Work in WP5 has concentrated on defining the key variables and relate these to relevant stakeholders to the E-COMPARED project in order to generate a route map to the future development of guidelines and recommendations. The variables are related to the stakeholders that have been identified in each country taking into account the information given by each partner involved in E-COMPARED. This framework will enable for synthesising the clinical output from WP2, cost-effectiveness assessments from WP3 and personalised modelling from WP4 into tailored information for interested stakeholders.

Work in WP6 concentrated on developing a dissemination plan, a project website and setting-up a stakeholder and dissemination database and initiate and monitor dissemination activities of the consortium. Various elements of the E-COMPARED project have been presented and discussed at over 40 national events and meetings, 4 international events and in 4 scientific publications.

The project management (WP7) focused on setting up the management structure develop planning and reporting procedures, templates and communication tools, and organising the consortium meetings including the kick-off and general assemblies. From the start and onwards, the consortium, research teams and individual researchers appear to be very skilled, enthusiastic and committed to bring E-COMPARED to a success and to innovate mental healthcare in Europe to the benefit of the patient and society.

The following sections provide a detailed account of the progress and work performed within each of the work packages. Deviations from the DoW are discussed and appropriate measures and solutions are proposed.

WP1: Adult depression treatment in primary and routine specialized mental care services WP1 activities are finalised and the deliverable D1.1 has been submitted to the Commission’s services. This is a major achievement as deliverable D1.1 provides a European overview of the current state of treatment as usual of adult depression treatment (TAU) in routine practice; Internet-based treatment for depression and blended treatment of depression (bCBT). Beneficiary 2 LiU (prof. dr. Gerhard Andersson and mrs. Naira Topooco) has coordinated the work. WP1 concerned four tasks:

Task 1.1: Current state of mental health policies and depression treatment delivery In spring 2014 the E-COMPARED consortium collected and assessed the current state of mental health policies and depression treatment service delivery in eight European countries. Through a literature review of local available and grey literature, each country was to account for data on costs, financing, regulatory approaches and service organisations for primary care and specialised treatment services. This information is compiled in the form of 8 country reports (CH, DE, EN, ES, FR, PL, NL, SE). The work is completed in month 12.


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Task 1.2: Consultation with stakeholders: stakeholder survey In spring 2014 we organised an online survey according to the project with various categories of national and European stakeholders, such as representatives of patient organisations, treatment providers, health policy makers, funding institutions and enterprises in Internet treatment. The survey was conducted in a subset of eight European countries with different health care systems and access levels of standard and internet-based depression treatment (France, Germany, The Netherlands, Poland, Spain, Sweden, Switzerland and The United Kingdom). The aim with the survey was to explore stakeholders’ knowledge, attitudes, behaviour and expectations regarding standard and internet-based treatment for depression. The survey was open March to June 2014. The data was analysed, and a first draft of the report was written in July-October 2014. In total 186 stakeholder organisations from eight countries participated in the survey. Findings show a gap between recommendations and distribution of depression treatment in Europe, marked differences on the availability and support for internet-based therapy in participating countries, and preference for blended therapy over internet-based therapy as treatment for adult depression.

Task 1.3: Secondary analysis For task 1.3 we updated the current available work in the domain of Internet-based and blended treatment of depression. For this update we conducted a systematic review. The systematic review shows as well that the number of studies assessing the clinical and cost-effectiveness of blended treatment of adult depression in routine practice is still very low. Those studies that report on blended treatment do provide promising results in terms of clinical effectiveness. They also show that that is a gap regarding clear descriptions on what the blended treatments exactly entail in terms of face to face versus online components. This update/MS will be submitted for publication in an international peer reviewed journal in 2015/2016 on behalf of the Consortium. The results of this update have been used as input for WP2 in terms of underpinning of the design chosen, power calculation, expected effect sizes, clinical and cost-effectiveness measurements to be applied and insights into comparability of outcome measures and natural course of depression (WP3 and WP4).

Task 1.4 Individual patient data meta-analyses (IPDMA) For task 1.4, a sophisticated meta-analytic strategy has been used to answer critical questions such as what characteristics predict patients’ response to treatment or patients dropout web-based psychotherapeutic trials. The aim of the present IPDMA was twofold. Firstly, we examined predictors of treatment outcome in self-guided web-based interventions for depression. Secondly we aimed at identifying predictors of treatment response (defined as 50% symptoms reduction from baseline) in self-guided web-based interventions for depression. This IPDMA analyses provides input in answering questions about which groups of patients may profit from blended treatment for depression or from TAU, and those who don’t and against which costs.

An existing database (1.VUA.evidencebasedpsychotherapies.org) on psychological treatments for depression was used and extended. This database has been developed in 2006 and it is updated yearly by electronic literature searches in PubMed, Psych Info and Embase and Cochrane Central Register of control trials.

For task 1.4, the database has been reviewed, updated and extended using literature searches. Various terms of psychotherapy and depression were used in different combinations (both index and free terms. The current IPDMA included data from in total 1,467 individuals from 8 studies. All the included self-help interventions were delivered


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through the Internet and were based on four different theoretical models of psychotherapy.

The preliminary findings indicated that only adherence was significantly related to treatment response. No other significant associations were identified. Overall, these preliminary findings should be interpreted cautiously. However, the findings suggest that patients should not be excluded from web-based interventions based on clinical (severity of depression and comorbid anxiety symptoms) and demographic (gender, age, education, relationship and employment status) characteristics since none of them seems to be related with treatment outcome or response. Moreover, an extra effort should be placed on retain participants into the intervention to maximize the chance that he/she will achieve a positive therapeutic outcome.

Involvement of partners and resource allocation 2.LiU (WP leader) developed guidelines for creating the eight country profiles for Task 1.1. All partners developed and revised their national report. 2.LiU collected and edited the national profiles into one report. All partners recruited names and contacts of stakeholders and uploaded the information on the stakeholder into the stakeholder database (see WP6). 2.LiU developed the guidelines for target groups and recruitment. 2.LiU also developed, launched and operated the survey questionnaires for CH, DE, EN, ES, FR, PL, NL, SE. All partners translated the survey to their local language and back translated the free-text fields of the survey to English for the analysis. 2.LiU performed the statistical analysis of data. The 1.VUA collected the data for the secondary analyses (T1.3) and the individual patient data from all the guided and unguided web-based interventions for depression (T1.4). All partners provided their relevant patient-level (anonymised) data to be pooled. The 1.VUA performed the review and analyses. 2.LiU developed the resulting Deliverable D1.2 for which 1.VUA assisted in quality control and adherence to DoW. All partners reviewed the draft of the aggregated analysis and report and approved it for submission to the Commission’s Services.

Beneficiary 1.VUA 2.LiU 3.FAU 4.LSHTM 5.InGeest 6.UJI 7.ULG Resources

spend 5.14 18.47 1.57 6.04 4.07 0 0

Beneficiary 8.UL 9.UBERN 10.UVEG 11.SWPS 12.INESC 14.Gamian 15.INSERM Resources

spend 0 2.5 8 24 0 0 3.36

Please note that 6.UJI, 7.ULG, 8.UL, 12.INESC and 14.Gamian are not included in the report and hence did not perform a task within WP1; the report covers only those countries who are also performing a trial.

Status and deviations from the DoW The report for Deliverable D1.2 and the results of Tasks 1.1, 1.2 and 1.3 results were discussed in consortium meeting in Valencia, October 2014. The work was finalised in November 2014. A high number of organisations (N=186) participated in the survey. This intensified the workload. The work for the IPDMA was delayed with 5 months for which agreement with the Project Officer was reached. An updated version of Deliverable D1.1 has been submitted to the Commission’s services in June 2015.

WP2: Comparing the clinical and cost-effectiveness of internet-based treatment and TAU WP2 is coordinated by beneficiary 1.VUA (prof. dr. Pim Cuijpers, dr. Annet Kleiboer, dr. Jeroen Ruwaard, and prof. dr. Heleen Riper) and has made good progress. WP2 consists of 8 tasks. Tasks 2.2-2.5 are to prepare for the eight trials and have been completed. Two major achievements have been delivered: the generic multi-site study protocol (D2.2) and


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the report on piloting the technical treatment platforms (D2.3). Therapists are recruited and trained and the trial sites continue to recruit more therapists. A database and database management system has been employed as well as a multisite randomisation procedure. All trial sites (PL, SE, DE, NL, UK, SP, CH) have started to recruit patients for the trials or are about to start recruitment (FR). In total 219 patients are recruited until now and the recruitment (task 2.6) proceeds slower than planned, which will lead to a delay in task 2.7 (conduct the trial) and task 2.8 (statistical analyses). A justification and proposal for next steps are presented below. First an account is given of the work progress for the specific tasks and how the trials are managed within E-COMPARED.

Task 2.1 Adaptation of existing internet-based treatment platform to local trial setting At the eight participating trial sites of the E-COMPARED multicentre trial, four different ICT-platforms are used to deliver the online treatment sessions: ICT4Depression/Moodbuster (DE, FR, NL, PL, UK), Deprexis (CH), Iterapy (SE) and Smiling is Fun (ES). All platforms are adapted, extended and refined to the project’s requirements and ready to deliver blended depression treatment. The platforms include: (1) an interface that enables communication between computer, mobile, and face-to-face, (2) an updated graphical design for both the client and therapist side of the platform, (3) EMA and mobile components, and (3) language and localization. The adaptation and refinement concerned amongst others the following activities: - Implementation of a Patient portal by evolving the existing platforms according to the

new specifications and specific requirements from trial sites; - Implementation of a new therapist portal according to specifications resulting from the

requirements of the trial sites; - Evolving the database model and secure web services layer to support all the client

applications: patient portal, therapist portal and mobile App; - For the ICT4Depression/Moodbuster platform: evolving the content generator in order

to allow for the translation and customization of the Moodbuster contents in the languages of the respective trial sites: English, Dutch, German, French and Polish;

- Refining patient and therapist portals according to comments received from pilot sites validation; (6) Implementation of data export mechanisms in the Therapist Portal to support researchers in their data analysis tasks;

- The ICT4Depression/Moodbuster platform is migrated to secure cloud services in order to face performance, reliability and scalability requirements.

The development of the ICT4D/Moodbuster platform has been initiated in the FP7 funded ICT4Depression project (GA 248778) and with the work performed in E-COMPARED, the platform now is a sustainable product and used in five European health care settings. This is a major achievement.

Task 2.2 Conduct 8 pilot studies to test clinical settings and ICT platform setup(s) and to tune parameters at each participating trial site To ensure the proper functioning of the four treatment platforms that are used in E-COMPARED, each platform was systematically tested for the system support of critical trial requirements by test teams throughout Europe, at local trial sites, in naturalistic settings. The technical pilot-studies were driven by a detailed common test-script that evaluated the technological readiness of the platforms, the usability of their user interfaces, their compliance to local and EU privacy regulations and their compatibility with local ICT configurations. More than 750 tests were run in the eight countries. This revealed numerous bugs and usability issues, which, in most cases, could be resolved by system developers on short notice (see Deliverable D2.3 for a detailed account of the pilots). On completion of the pilot tests, some critical recommendations remained to be implemented for


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ICT4Depression and Smiling is Fun. These were addressed and resolved prior the scheduled start of trial participant recruitment in each site. None of the trial partners rejected their system. As a result of the pilot test all partners concluded that their systems were usable for trial and treatment purposes as planned for in the E-COMPARED project. Additionally, the scheduled systematic technical pilot tests led to very efficient and focused development efforts that ensured technical treatment delivery platforms that posed no barriers for the E-COMPARED project to enter the trial recruitment phase. These studies prevented patients and therapists to be exposed to unnecessary technical problems.

Given the number of critical issues that were raised, identified, and resolved during the pilot-test process and the positive outcomes of the resolving efforts and attitudes of the developers and users, we recommend future e-health projects to follow the systematic test-script-based procedure similar to what is applied in the E-COMPARED project. In addition to ensuring on-going technical support during the trial, current technical efforts focus on the realization of export of data for explorative satellite studies (i.e., to study the relationship between system usage indicators and outcome). On the next E-COMPARED Project Meeting (October 2015, Porto, Portugal), both issues are put on the agenda.

Task 2.3 Develop a multi-site study protocol The multi-site protocol is finalised and delivered to the Commission’s Services in month 9. As described in Deliverable D2.2, the basis for the generic multi-site study protocol was set at the kick off meeting. Issues were inventoried regarding the basic features such as target population, inclusion and exclusion criteria, randomisation strategies, measurements, time points and data handling. The successive months were used to set-up a generic protocol that was both feasible and able to meet the study objectives. This included a questionnaire for the participating trial sites to provide additional information on e.g. regulations, target population, intervention composition etc. The generic protocol sets for the minimal methodological requirements including the design of the study, target populations, conclusion and exclusion criteria, randomization procedures, primary and secondary measures, treatment descriptions of both blended and TAU treatment, measures on treatment fidelity of patients and providers, methods of analyses as well as information to patients about the study informed consent procedures and privacy regulations. Several WP meetings took place to fine-tune requirements, study design and treatment protocol issues. The development team is preparing to publish the protocol to a peer-reviewed journal.

Task 2.4 Study protocols for approval to the scientific and medical ethics committees Partners at each trial site have developed local versions of the study protocol that is adapted to their specific situation and language while still meeting the requirements set by the generic study protocol. All countries have now obtained approval for conducting the trial from their local Medical Ethical Committees, and these are registered in a Trial Register (registration of the French trial is still pending). More information including the approval letters from Medical Ethical Committees and trial registration numbers can be found in Deliverable D2.2. Trial registration numbers are included in Annex 3 of this report.

Task 2.5 Training of professionals in treatment and study protocol fidelity All trial sites developed training protocol in line with the generic study protocol. The aim of this training is to educate therapists in both providing the blended treatment and in working with the platform. Therapists at all trial sites have been recruited and are trained locally to deliver the treatment according to protocol and are familiar with the study objectives, procedures, and their role in the study. Treatment fidelity is ensured by (1) the detailed treatment manual that is available for therapists, (2) regular meetings between


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therapists and the research team to prevent drift, (3) a brief questionnaire on the number of sessions, the frequency of sessions, the main strategies used in each session, the duration of the contact, and whether they have referred the client to the online website in each country that is completed by therapists after each (face-to-face) session. Therapists’ activities on the platform will be assessed by tracking functionalities in each trial site through the log-files of the platforms.

Task 2.6 Recruitment and selection of patients at trial sites Study participants are recruited in primary care (ESP, SE, DE, PL, UK) or specialized mental health care (CH, NL, FR). Specific recruitment procedures depend on the country and the setting, but all countries apply the same inclusion and exclusion criteria. Recruitment, selection of patients, and randomization procedures are described in detail in the generic protocol.

Participants that are eligible to take part are randomized to blended depression treatment or treatment as usual which is defined as the routine care that participants receive when they are diagnosed with depression in that treatment setting. In practice that means that treatment as usual may vary between countries, treatment setting, and among patients, and not always equals standard treatment guidelines.

Randomization takes place centrally by 1.VUA for most countries with exception of FR where the randomization procedure is automatized, and the UK where a local independent researcher is appointed to perform the randomization.

Task 2.7 Conduct of eight randomized clinical trials An international multi-center trial as performed in E-COMPARED, needs attention in three distinct but related dimensions: 1) trial logistics and protocol, 2) technical platforms offering treatment, and 3) data management. Additionally, the trials need coordination on two levels: on a central level and on site or local level. As such, the management structure includes both central trial coordinators as well as coordinators at the individual trial centers. For proper conduct and management of the trial (and its preparations), the PMT together with the Executive Committee issued an extension of E-COMPARED’s management structure early in the course of the project that caters for central trial coordination, technical coordination and data management. The organogram in section 2.3 provides a graphical overview of the structure.

Central coordinators have the task to manage, control and report on the international multi-centre trial on a central level. As such, the areas of concern for the Trial Protocol Coordinator include the development of generic study protocol; obtaining the required ethical approvals and trial registration at relevant registries; therapist and patient recruitment; adherence to generic protocols; and the stopping rules;

Areas of concern for the Technical Platforms Coordinator include the development of treatment platforms in accordance with generic study and treatment protocol including appropriate translations of interfaces; technical testing of platforms in terms of technical reliability and usability; interface with data acquisition procedures and databases; and ensuring servicing when issues arise during execution of the trials.

Areas of concern for the Data Management Coordinator include the development and maintenance of central database for pooling data from local databases; interfacing with local databases; interfacing with technical platforms; development of data safety, data quality, and data issuing procedures.


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Each central coordinator developed and maintains an Action Plan detailing the -) (sub)tasks based on task descriptions in DoW; -) deliverables and milestones and -) a detailed planning.

Each site coordinator is instructed by central coordinator and reports correspondingly. Central Coordinators report to WP2 leader and PMT. PMT report to Executive Committee and Trial Steering Committee.

The local site coordinators are responsible for all operational aspects in conducting the local trial. The central coordinators are responsible for providing the local site coordinators with relevant information and advice so they can operate the trials in line with the DoW and the planning.

Data management To enhance integration of data from the different trial sites, central data management (1.VUA/5.InGeest) has performed the following tasks: - Construction of a domain format for data files and their content (file and variable

names and content). - With this format, a ‘codebook’ document was constructed, with the necessary

variables and values to be provided to central data management by local trial data-managers.

- A website tool – Psydata- was established with which data files can be uploaded safely at each site to central data management. The same tool will be used to eventually issue cleaned and pooled data files to researchers who use E-compared data on request.

- Skype meetings were held to instruct local data managers concerning the mode and content of data delivery with this tool.

- Preparations are started for data cleaning and -labelling, scale construction, documentation. Some data files are already uploaded with the tool.

Task 2.8: analysis of the results This task will commence as soon as the inclusion of patients has ended and the data has been collected in the central database.

Involvement of partners and resource allocation The 1.VUA led for task 2.1 the design of the technical requirements and coordinated the alterations of the platforms. 8.UL has contributed to the technical development required to prepare the Moodbuster platform. INESCO adapted, extended and refined the Moodbuster platform. 9.UBERN adapted the “Deprexis” platforms to requirements; 2.LIU adapted the “Interapy” platform to requirements. UPEC adapted the “Smiling is fun” platform to requirements. For the piloting and testing the platforms (task 2.2), 1.VUA designed the test scripts and reported on the findings. All eight trial sites consented, executed on the testing, and reported on the local findings. For developing the generic protocol (task 2.3), the 1.VUA initiated, coordinated and processed all input on draft generic multi-site study protocol. All trial site partners provided additional information through a dedicated questionnaire. All trial partners and platform developers have provided feedback on contents and feasibility of the generic protocol and compatibility with the technical platforms. Based on the study protocol, 5.InGeest together with 1.VUA developed a treatment protocol including training material that has been translated and used by the other sites to develop their treatment protocols. The trial sites recruited and trained the therapists (based on materials developed by 5.InGeest and 1.VUA) and all trial


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sites are recruiting patients. 1.VUA developed and performs the randomisation procedure. 5.InGeest together with the 1.VUA developed the database management system and procedures.


spend 33.69 22.4 30.67 9.30 13.52 46.94 4.69


spend 27.18 22.08 7 25.23 34.53 0 10.13

Status and deviations from DoW Deliverable D2.1 and D2.2 are delivered to the Commission’s Services as planned. Because some health care systems appeared to be more open to blended treatment than anticipated in Sweden, this trial site started the study in primary care instead of secondary care. Regarding the generic multi-site study protocol, the consortium decided to diverge from the DoW for the times to follow-up (3, 6, and 12 months) because this better matched with the length of treatments and is more in line with current knowledge available literature in which follow-up times of 6 and 12 months are most common.

Two issues arose during the inclusion of patients:

1) Start of recruitment was planned for month 13 (February 2015). Trial sites SE, DE, ESP, CH started recruitment as planned in month 13 or shortly thereafter. Four trial sites (PL, NL, UK, FR) were not able to start with recruiting patients in month 13. The main reasons for the delays were due to 1) the complexity of the treatment (face-to-face and online sessions) leading to issues with setting-up the local treatment- and study procedures in some care settings, and 2) due to interpretation and adherence of the technical platforms to (new) safety and privacy regulations. Ethical approval is obtained for all sites and as such, D2.3 will be updated on request.

2) The inclusion of patients is slower than anticipated (per trial site and overall). In addition, inclusion rates differ per country and care setting (see figure 3). The period of recruitment (month 13-20) was based on an average inclusion of 5 participants per week (20 per month). Currently the average recruitment rate is 1,5 participants per week (6 per month). Recruitment rates decreased during the summer period as well (July-August) but are expected to increase as all trial sites are looking to for example including additional mental healthcare clinics, increase awareness amongst referrers, et cetera.

Figure 3: inclusion and randomisation rates


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These two issues lead to a number of scenarios to guarantee inclusion of the required numbers of participants. The following is currently under consideration: 1) Extend inclusion period with seven months, which equals the delayed start of

recruitment for trial sites UK, FR and NL. This will however lead to a less then expected numbers of participants to be included as the recruitment rate is lower then expected and thus may lead to potentially underpowered studies on a national level studies. We may partly overcome this problem, as we will pool the data of the national studies so sufficient statistical power will be obtained for the aggregated analyses.

2) Extend inclusion period with 12 months, which both caters for the delayed start of recruitment and adheres to a more realistic recruitment rate than anticipated as the total inclusion period increases with 5 months. This way we expect the national level studies and the aggregated level both to be adequately statistically powered.

Besides these two options, the consortium considers the possibility to provide clinical data depended tasks in WP3 and WP4 (e.g. model validation) with preliminary data in other for them to develop the models based on simulations informed with real but limited data. The models can then be validated without much delay when all clinical data arrives. Reporting on methodologies and preliminary results is considered to be an option.

The consortium will discuss and decide on this issue in the third Consortium Meeting in October 2015 and subsequently seek the Commission’s advice and agreement on how to proceed.

WP3: Economic modelling studies Based on new insights, the WP3 team discussed and decided to extend the work and resulting deliverable to also include Discrete Event Simulation (DES) modelling. This enables to compare both generic models and include the results of both in the synthesis in WP5. This decision has been taken in accordance with the recently published literature and following a systematic literature review carried out by the work package 3 members, which results are presented below (see Task 3.2.1). The work package is led by Beneficiary 15.INSERM (dr. Karine Chevreul). The following tasks have been executed in accordance with the DoW.

Task 3.1. Literature review on the course of depression and its treatment A systematic review and meta analysis has been performed to examine the positive (remission from depression, response to treatment) and negative (deterioration of depressive symptoms) effects of TAU on MDD. The results will provide input in the economic modelling in WP3 further on.

In the analyses of 38 studies including 2,099 patients with MDD receiving TAU, we found that 27% of the patients remitted from depression at the end of the treatment. Studies that used intention-to-treat analysis reported lower remission rates (0.21) than studies that did not use a method to handle missing data (0.42; p<0.000). The multivariate regression analysis revealed that the within-group effect size for depression was a significant predictor of remission rates. After TAU, 28% of the patients showed an improvement in depressive symptom severity. Finally, 12% of the patients suffered from deteriorated depressive symptomatology at the end of treatment.

Therefore we concluded that many patients can benefit from TAU for MDD, but also a small number of patients suffer from worsened depressive symptoms at the end of the treatment. We recommend that researchers provide a thorough description of the TAU offered to patients.


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Task 3.2. Development of a model to describe the natural course of depression For task 3.2 the results from task 3.1 are used to define the states that describe the natural course of depression in order to build the structure of both the Markov and the DES models. In a second step, based on clinical trial protocol developed in WP2, for each model, treatment strategies will be defined that include the Internet-based ‘blended’ depression treatment. The content of treatment of usual (TAU) will be based both on the trials executed within E-COMPARED and the review in Task 3.1.

Following discussions among WP3 members, the task 3.2 has evolved and has been divided into three subtasks as follows: - Task 3.2.1. Literature review comparing modelling techniques to perform cost-

effectiveness analyses in the field of depression - Task 3.2.2. Development of a Markov model (MM) to describe the natural course of

depression - Task 3.2.3. Development of a Discrete Event Simulation (DES) model to describe the

natural course of depression

The work performed for each subtask and the reasons of this deviation are described below.

Task 3.2.1. Literature review comparing modelling techniques to perform cost-effectiveness analyses in the field of depression A recently published literature review concluded that DES modelling would be more suitable than MM to perform cost-effectiveness analyses when individual patient history may considerably impact future events (Standfield et al., 2014). These new insights gave rise to discussion among WP3 members regarding which modelling technique would be the best fit to carry out a cost-effectiveness analysis to address the objectives of WP3.

Following these discussions, a literature review has been conducted to take an inventory of the strengths and weaknesses of MM and DES models, in particular when they are used in the field of depression but also in the context of other disorders.

Overall, advantages and disadvantages of the two models identified in the literature may be summarized as followed: the DES model has better ability to take into account patient history, events can occur simultaneously, and it has greater face validity due to the more realistic representation of disease course. Conversely, this model is complex and time consuming, populations need to be observed over a long period of time, and it has rarely been described in literature. The MM struggles to precisely capture the natural course of the disease but it requires less time and expertise to develop; it is more transparent, which permits more confidence to decision makers; and it has been used frequently in literature, which allows for better comparisons with previous studies.

Taking into account the review, the WP3 team decided to include both MM and the DES modelling the analyses of the data in WP3. The differences in results and in resource allocation decision will be compared and related to the differences in terms of practicability to provide empirical knowledge in supporting policy- and decision-making. This means that the work for Deliverable D3.4 will be extended to cover also the DES model.

In line with the DoW and now for both models, a cycle length based on the timing of critical events in the course of depression will be used. The effectiveness of the treatments will be expressed in Quality-Adjusted Life Years (QALYs) and percentage of patients who recover from depression. The costs will be assessed from the perspective of health care payers (including two scenario, all payers (statutory health insurance, private health insurances, and patient out-of-pocket expenses) and only public funders), and the societal


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perspective (including the costs assessed through the “all payers” perspective and the indirect costs of productivity losses). Cost-effectiveness planes presenting the simulated incremental costs and effects of the Internet-based ‘blended’ depression treatment by comparison with the “TAU” will be created. Cost-effectiveness acceptability curves will also be estimated to show the probability of the Internet-based ‘blended’ depression treatment being cost-effective at different values of willingness to pay.

Task 3.2.2. Development of a Markov model (MM) to describe the natural course of depression The literature review performed in Task 3.1 allowed the identification of several health states/events that have been used in cost-effectiveness analyses to describe the natural course of depression. Among them, the states/events “response”, “remission”, “relapse” and “death” were the most used. Several states are identified as being relevant but discussions are on going on their precise definition to allow the description of the natural course of depression. In particular, in order to ensure the mutually exclusive and collectively exhaustive nature of health states required in a MM, the measurement tools and the related thresholds are currently under development for the states response and remission. Meetings with clinicians have been planned for that purpose.

For the technical implementation, the WP3 team decided to assess the level of adaptation of an existing Cohort MM developed by the Trimbos Institute in The Netherlands. This model is dedicated to the modelling of depressive disorders and called DepMod (Lokkerbol et al., 2014). In order to assess the reliability of adapting the DepMod model to the objectives of the E-COMPARED project, members of the 15.INSERM team attended a workshop with the authors of the model on the 20th of August 2015.

Task 3.2.3. Development of a Discrete Event Simulation (DES) model to describe the natural course of depression The review conducted within Task 3.1 has supported us in identifying important events that should be included within the model (health states like remission, recovery, relapse, etcetera). An unstructured review of the literature resulted in an overview of attributes that should be included in the DES model. These attributes are characteristics of patients that are simulated in the model. Attributes that will be taken into account are well-known risk factors for depression such as the number of previous depressive episodes, severity of depression symptoms and duration of depressive complaints. The next step is to create a framework for the DES model and, subsequently, to implement it.

Development of a DES model was not included in the DoW. However, based on the literature review described in Task 3.2.1 it was decided to also develop a generic DES model, because this type of model offers great advantages in handling different patient profiles, multiple events and complicated scenarios through the more flexible handling of time.

Tasks 3.3 – 3.8 These tasks are pending the development of the generic Markov and DES models and planned for to start in reporting period 2.

Involvement of partners and resource allocation The 1.VUA (dr. Judith Bosmans, Spiros Kolovos) together with the team at 15.INSERM have conducted the literature study described in task 3.1. The subsequent discussion was lead by 15.INSERM and all WP3 team members and the PMT were involved. The study investigating the health states for DES has been performed by 1.VUA (dr. Judith Bosmans, Spiros Kolovos) in collaboration with 8.UL (prof. dr. John Forbes).


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spend 11.93 0 0 0 2.08 0 0


spend 0 0 0 0 0 0 5.73

Please note that the involvement of prof. dr. John Forbes (8.UL) is not claimed under the E-COMPARED project as his position is contributed in-kind to the project.

Status and deviations from DoW Considering the review conducted in the course of task 3.2.1, the WP3 team choose to extend the work for WP3 to include both Markov and DES modelling. The benefit from this for the E-COMPARED project and its stakeholders are: 1) Ensuring comparability of the E-compared project results with the published articles

having performed cost-effectiveness analyses using MM and/or DES models; 2) Provision of knowledge, based on empirical comparisons, about the impact of the

modelling technical choice on: the cost-effectiveness analysis results; the resulting resource allocation decision; and the time, data and human resources requested: • If the MM and the DES model give similar results and lead to the same resource

allocation decision, the fact that the DES model is more time, data and human resources consuming would conduct to recommend the use of MM for policy decision making in the field of depression.

• If the DES model appears to be more relevant to describe the natural course of depression and provides more accurate results than the MM, then the empirical comparison of the two models in terms of results and practicability (time, data and human resources requested) will allow assessing the incremental cost of providing more precise information.

Due to the importance and scientific benefit of investigating both models in the framework of E-COMPARED, the involved partners decided to budget neutrally perform the extra work and proposes to extend the delivery date of Deliverable D3.4 from month 24 (December 2015) to month 27 (March 2016). There are no negative influences foreseen to other work and work packages other than a short delay of the related tasks in WP3, notably tasks 3.3 and 3.4.

WP4: Personalised Depression treatment modelling WP4 runs on schedule. WP4 is lead by beneficiary 7. ULG (prof. dr. Burkhardt Funk) closely collaborates with 1.VUA (dr. Mark Hoogendoorn and dr. Michel Klein) in modelling personalised treatment for depression and with 12.INESC (dr. Artur Rocha) to build the technical infrastructure. Since data collection is still on-going in WP2, datasets from other studies and simulated data are used to develop and estimate predictive models. On March, 23rd and 24th, 2015 we had a 2-day workshop in Lüneburg to discuss intermediate results and future directions of WP4. The work in WP4 is divided in 4 tasks of which 3 tasks have started in this reporting period.

Task 4.1: Development of knowledge-based predictive models Progress towards objectives: The focus has been on developing techniques to tailor a computational model, called virtual patient model, which is based on existing theories in clinical psychology. Hereby, parameter estimation techniques have been developed, resulting in the publication R. Kop et al. (2014).


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The virtual patient model has been implemented in the statistical programming environment R to simulate datasets. These simulation routines have been shared across the participants involved in WP4 and used to evaluate the methodology developed in WP4.

During the last months, extensions have been developed to the virtual patient model in four ways. First, the concept of emotion regulation has been included to reduce the influences of negative events on the mental health state of a person. Emotions can be regulated in variety ways. This extension combines the short-term emotional reaction on stressful events with the long-term dynamics of mood. A re-interpretation (reappraisal) emotion regulation strategy is used to regulate emotions by re-interpretation of negative events (Gross, 2001). It involves changes in beliefs and the level of negative feelings.

Second, the effect of social support on appraisal and re-appraisal of negative events has been included. This extension explores the role of stress buffering and main effect models put forwarded by Cohen & Wills in 1985. Social support can either refer to the social resources that individuals perceive to be available or to the support that is actually provided in problematic situations. The proposed extension distinguishes between both roles of social support.

Thirdly, an extension is explored in which the online social support seeking process is modelled. This involves online self-efficacy (the ability of a person to seek support via online social networks) and the positive outcome expectations, which increase online activity to seek support through online social networks. It also increases the perception of the availability of online support. This work is still on going.

In the fourth extension, which is still in progress, the characteristics of the social networks (e.g. strong tie relations, weak tie relations, size, density etc.) and the role of perceived companionship are related to a person’s participation in positive social activities. Participation in social activities and maintaining social (network) relationships with community are frequently seen as indicators of happy and healthy life and it is widely accepted that a strong social network, social support as well as companionship have a strong protective effect on health. People usually have different social networks to which they are attached with different ties. Purpose of this study is to develop a model that can better predict mental health (depression trajectories) and can assess the effectiveness of social factors on mental health (mood) and able to suggest/ support the people about health related and social activities.

The four extensions will be validated later in the project within smaller user studies and / or with data collected during the trials.

In addition, joint work to map the current landscape of predictive modelling in mental health has been started to gain a good insight into the current methods as well as opportunities to move beyond the state of the art. As a result we developed a framework to categorize predictive modelling in e-Mental-Health.

Furthermore, we have used a combination of document classification and text mining techniques to implement an exploratory tool to perform sentiment analysis, over a collection of resources gathered in the scope of therapy, against a given lexicon file.

Task 4.2: Development of distributed infrastructure Progress towards objectives: An intensive collaboration has been set-up between 12.INESC, which is responsible for the storage infrastructure in WP2, 7.ULG, and 1.VUA, thereby discussing the setup of the infrastructure to generate predictive models. Several discussions with 12.INESC on available data and its format have taken place to facilitate a smooth process once the data from the trials becomes available. Currently, in this task, we


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evaluate and discuss ways to use the multi-criteria optimization framework described in Task 4.3 to estimate predictive models at scale. After answering the question to what extent additional computational power help to increase the predictive capabilities of models like those developed in Task 4.1, we will work on how to parallelize the optimization framework.

Task 4.3: Improvement of predictive models Progress towards objectives: The main focus has been on the development of more fundamental machine learning techniques that can be used to generate accurate predictive models for therapy success. Here, the main goal has been to develop techniques that allow for more fine-grained predictions of the mental health state of the patient. Having such fine-grained predictive models not only allows prediction of the most suitable therapy, but also prediction of the course of the depression. The latter establishes the possibility of identification of patient clusters by means of their depression trajectories (contributing to task 4.4). At this stage, there is no data available from the E-COMPARED trials; therefore other datasets have been used to evaluate model performance. One dataset is from one of the clinical partners in the project, prof. dr. Matthias Berking (3.FAU). Results are promising and have been published in R. Kob et al. (2014). Next, a framework has been developed to evaluate fine-grained predictive models in an accurate way (Breda et al. 2015). This framework allows estimating the parameters of dynamic models using multi-criteria optimization. In addition, data obtained from the EU-funded project GET.ON (7.ULG) was used to examine the predictive power of the virtual patient model compared to more generic modelling approaches. This includes advanced methods for time series analysis such as state space models or hidden Markov models as well as established methods from Machine Learning such as support vector machines and decision trees. Results indicate that the predictive power of the two approaches (top-down/virtual patient model vs. bottom-up/generic ML methods) is comparable.

Task 4.4: Patient cluster identification This task will commence once clinical trial data from WP2 are in the central database.

Involvement of partners and resource allocation 1.VUA tailored the computational model for benefit of task 4.1. 7.ULG developed the R based simulation code. 12.INESC implemented the text-mining tool.

12.INESC is responsible for the data infrastructure. 7.ULG and 1.VUA bring in their work from tasks T4.1 and T4.3 and develop and evaluate ways to parallelize model estimation. The amount of resources used somewhat exceeds the anticipated amount of resources. This can be fully explained by the number of PM’s that exceeds the original planning. The main cause if this is that we have performed more of the theoretical developments of the predictive modelling approach at this stage than we initially planned. We do not expect this to cause any problems in achieving the WP objectives as the research is currently at a much more advanced stage than we anticipated at the start of the project. Hence, fewer resources will be needed for the second period of the project.


spend 49.16 0 0 0 0 0 9.6


spend 0 0 0 0 3.1 0 0


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Status and deviations from DoW Content-wise there are no deviations. From a technical perspective we are in the process of investigating whether the newly developed algorithms are feasible to run without a distributed infrastructure. Having said that we might not have the necessity to set up a Hadoop cluster and use MapReduce as the computational backbone. However, computational complexity for estimating models is high and we currently evaluate and discuss a concept for distributing the model estimation process.

WP5: Synthesis of results, EU recommendations and business case development Beneficiary 6. UJI (prof.dr. Cristina Botella) leads WP5 and closely collaborates with 10.UVEG (prof.dr. Rosa Baños), 1.VUA (prof.dr. Heleen Riper, Christiaan Vis) and 9.UBERN (prof.dr. Thomas Berger, dr. Tobias Krieger) in developing the framework for the synthesis of results. WP5 runs on schedule and consists of 8 tasks. Work on tasks 5.2 – 5.8 start after month 18 when results from WPs1-4 are available.

Task 5.1: Design of data-analytic format and results of WPs 1-4 For the first reporting period, the effort of WP5 team was focused on completing task 5.1. This task aimed to develop a first draft of key variables and relevant stakeholders involved in the E-COMPARED project in order to generate a route map to the future development of guidelines and recommendations. In order to achieve this objective, WP5 has developed the following task and actions:

First, given the interplay with the other WPs in the project, several telephone conferences were organized in order to coordinate, share and exchange the information needed for the data-analytic format. Particularly, the task of identifying stakeholders and important outcomes are essential for several WPs, specially WP1, WP5 and WP6.

In order to elaborate the guidelines and recommendations, it is necessary to identify the relevant results that each WP will generate. In order to organize these outcomes, we analysed the purpose and objective of each WP to detect the key variables involved in the E-COMPARED project and generated a first categorization of relevant information. In a second step we requested feedback for each WP leader regarding this information. This categorization will be refined along the project according the WPs progress. This resulted in the variables presented in figure 4 relevant to each WP.

Figure 4: relevant variables for each WP


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A crucial task for the goals related to both WP5 and WP6 is to identify the relevant stakeholders (patients, policymakers, health care professionals, health insurers and employers) on an international and national level of the participating partners. Relevant stakeholders have been identified in each country taking into account the information given by each partner involved in E-COMPARED. The process followed to delimitate this information was addressed by WP1. WP5 has organized and developed a stakeholder categorization following the information collected by WP1 (see figure 5). It is important to

highlight that this information is a preliminary categorization that might change throughout the project depending on the new information and progress in the different WPs.

Based on the stakeholders’ analysis and our previous analysis of the key outcomes of each WP, a first organizational scheme was made. This scheme guides the development of the guidelines and recommendations. Table 2 shows the first scheme developed by the stakeholders per variable.

E-COMPARED aims to give an answer to several questions regarding the use of ICTs in the field of the treatment of depression. But the diversity of questions formulated whether the ICT treatment is more effective, or it is more or less expensive than the traditional treatment (TAU) is not important in the same way for all the stakeholders. In this sense, in order to know the information that is relevant for each stakeholder is an important issue for both, the generation of recommendations

and guidelines, and for the dissemination of the E-compared results. Table 2 seeks to organize this flow of information and the relationship between the key variables in order to prepare the information for its dissemination according to the profile and expectations of each type of stakeholder.

In correspondence with WP1, the stakeholders were characterised into six groups. Regarding the expected outcomes, we considered that researchers would be interested in almost all the outcomes of the project except on those related with the practical organization of the services or with the actual policies in mental health.

Care providers are more interested in those outcomes related to the current state of the Health system and the results that E-COMPARED will obtain regarding the comparison between both treatments (TAU vs. Blended) in their different aspects assessed (satisfaction,

Figure 5: Stakeholder categories


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efficacy, cost-effectiveness, etc.). In addition, the information generated regarding personalization will be important for them.

We expect the outcomes to be relevant to funders, especially to those related to the comparison among treatments and the impact in the patients and in the economy outcomes.

Technology providers will be more interest in the technical outcomes, but also those related to the efficacy of the treatment and the results on cost-effectiveness.

Consumers will be interested in the current state of the treatment and the results obtained when comparing both treatments, in particular those related to clinical outcomes.

Finally, governing the mental health care sector will be interesting in the outcomes obtained related to the current state of the mental health system, its treatments, and the efficacy of those. The results will also be important for them in terms of economic and clinical outcomes of the treatments and their impact.

All the work done was reviewed by the WP-leaders and the feedback received was considered in order to improve the analytical framework. In order to establish the best way to deliver the information to the stakeholders, different dissemination strategies were elaborated. In this sense, several teleconference meetings were organized with WP6 (dissemination) in order to start the definition of the different dissemination strategies to be done.

Please note that the above-mentioned framework is work in progress and will be refined in the coming months.

Tasks 5.2 – 5.8 These tasks will commence as soon as the data from the clinical trials (WP2), economic modelling (WP3), and patient modelling (WP4) are ready and transferred to WP5.

Involvement of partners and resource allocation All partners were involved in defining the stakeholder categories and reviewing the first drafts of the analytical framework. WP-leaders were involved to ensure optimal connection with their work. Partners also engaged in actively involving stakeholders to enhance acceptance of eMental health when introducing Internet interventions to the current

Table 1: Variables related to stakeholder categories


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mental health practice requires more fundamental changes in mental health policies. For example, SWPS In Poland engaged in preparatory activities to increase stakeholders’ acceptance of the Guidelines and Recommendations. To achieve this goal, members of the E-COMPARED consortium take part in the organisation and scientific committees of the 3rd Meeting of the European Society for Research on Internet Interventions (September 2015, Warsaw, Poland). The relevant stakeholders participated in a pre-conference expert meeting with the representatives of the E-COMPARED research team.


spend 0.23 0 0 0 3.66 5.67 0


spend 0 0 0.02 5.8 0 0 0

Status and deviations from DoW Until now, there were not any deviation from the DoW in the work performed and the planning of the following steps is maintained as it was stipulated. The first task allowed us to made a preliminary planning for Guidelines and Recommendations. The work generated from the active WPs and the synergy between partners has started generating outcomes, so the planning of Guidelines and Recommendations will be constantly updated and deepened taking into account the new data during the execution of the E-COMPARED project.

Our next steps are oriented to the following task planned, the task 5.2 (analyse and combine results WP1-4). This task depends directly on the work of other WPs, given that implies the management of information generated by other partners. In this sense, we are planning to have a close communication among the partners involved and start to summarized and combine the data.

WP6: Dissemination The main objective of the work package (WP) 6 is to disseminate the project results to all relevant stakeholders and to maximize its exploitation potential. The specific objectives are (a) to define an integrated strategy for E-COMPARED dissemination activities, (b) to regularly inform all stakeholders about the project and progress, and (c) to offer a platform for continuous exchange of information with all stakeholders.

In the first reporting period the E-COMPARED project has been presented in more than 40 national occasions, 4 international meetings and 4 scientific publications.

So far, this WP is on track and there have only been minor deviations from the DoW.

Task 6.1: Development and maintenance of the dissemination plan. We developed a dissemination plan and are regularly maintaining it. Herein, we have described in detail the dissemination strategies with regard to target audiences, key messages, methods, frequency and responsibilities. Additionally, we have described the next steps of the dissemination strategies. Finally, we have created an online database in order to collect relevant stakeholders and a categorization of them. Please refer to the Dissemination plan for more information.

Task 6.2: Development and maintenance of the project website Since month 3 of the project the website is online and can be found under 1.VUA.E-COMPARED.eu. It includes a public and a private part. In the public part we inform about the project and the partners that are involved. Furthermore, we provide a list of dissemination activities that have taken place so far. In the secured part of the website,


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involved partners can download relevant documents and templates of the project. The homepage has been updated regularly. In parallel, we created dissemination materials such as templates for reporting and press releases, and also a twitter account. The design, technical implementation and functionalities are detailed in Deliverable D6.1.

Task 6.3: Execution of the dissemination plan We constantly execute parts of the dissemination plan. So far, the execution has been limited to provide information about the project. However, in the first reporting period the E-COMPARED project has been presented in more than 40 national occasions, 4 international meetings and 4 scientific publications.

Furthermore, a secured database for completed and planned regional/national dissemination activities of the regional partners is online; a regular reminder to update the database is sent to all the partners. We plan to disseminate these results from WP1 as first results from the E-COMPARED project as soon as possible via scientific peer-reviewed journals.

A list of all dissemination activities is included in Annex 2.

Involvement of partners and resource allocation 9.UBERN developed the dissemination plan. All partners provided input and reflection on the dissemination plan. Partners 9.UBERN and 1.VUA developed the website. 9.UBERN takes responsibility for maintenance of the website. All partners are included in the execution of the dissemination plan both on a central level and on a local level.


spend 1.15 0 0 0 0.73 0.3 0


spend 0.39 1.52 0.4 0.3 0 2.67 0

Status and deviations from DoW The DoW included the functionality of conferencing and real-time file sharing. At the kick-off the consortium choose not to include this in the website as there are good alternatives which are available for free (Skype, GoToMeeting, drop box, Google drive). For file sharing, we choose to include a secured repository (read-only) accessible by all partners as to prevent errors in synchronisation, unintended deletions and security issues. This approach proved both to be effective and efficient. Furthermore, we included a dedicated stakeholder database, local dissemination plans and a database for keeping track of the local dissemination activities. This database is also used for the stakeholder survey in WP1 T1.2 and for shaping the synthesis activities in WP5 – synthesis. The deviations mentioned have no foreseen negative impact on the budget of WP6 and tasks of other WPs.

2.3. Project Management All managing and coordinating activities are grouped in WP7 that aims to ensure a smooth execution of the project and compliance with the project plan (DoW). The guiding principle determining all project management activities for E-COMPARED has been that of decentralised, flexible decision-making. While day-to-day control of the project is in the hands of the Project Management Team, the responsibility for the project as a whole lies with the General Assembly and is supported by the Executive Committee.


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Management Structure For E-COMPARED, a three layered management structure has been installed and still is active (see the organogram presented in figure 6).

The General Assembly (GA) is the main decision making body in E-COMPARED and consists of one representative of each project partner. The GA advised the Executive Committee and Project Management Team during two Consortium Meetings and reviewed the project progress and results so far. Issues discussed included amongst others the Publication Policy, the liaison strategy with the MasterMind project and consortium composition.

The Executive Committee is responsible for overall monitoring of the scientific and financial progress of the project activities towards the main objectives of the project. All Work Package leaders are seated in this committee and report to the General Assembly. Work Package Leaders (WPLs) are responsible for the detailed management of the work packages within the budget of expenses and resources that is allocated to the work package.

Figure 6: Organogram E-COMPARED


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The Project Management Team is responsible for day-to-day management of E-COMPARED. Tasks range from liaison with the European Commission and with other projects and networks, to financial, legal and administrative support to the consortium.

Please refer to the table below to review the persons in charge.

Table 2: key persons involved in E-COMPARED

Work package Leader Affiliation 1. Adult depression treatment in primary healthcare and routine specialised mental healthcare services

Prof. dr. Gerhard Andersson

Professor of Clinical Psychology at Linköping University in the Department of Behavioural Sciences and Learning

2. Comparing the clinical and cost-effectiveness of internet- based treatment and treatment as usual

Prof. dr. Pim Cuijpers Professor of Clinical Psychology and head of the department of Clinical Psychology at the VU-VUmc

3. Economic Modelling Studies Dr. Karine Chevreul Head of ERASM (applied research team in mental health), deputy head of URC Eco and researcher in the Public health dept. of the Henri Mondor teaching Hospital

4. Personalised Depression Treatment Modelling

Prof. dr. Burkhardt Funk Professor for information systems research and vice president for Information Technology at Leuphana University Lüneburg

5. Synthesis of results, EU recommendations and business case development

Prof. dr. Cristina Botella Professor of Clinical Psychology at 6.UJI (Spain) and director of Labpsitec

6. Dissemination Prof. dr. Thomas Berger Professorship of the Swiss National Science Foundation on internet-based treatments / eMental health, Institute of Psychology, Bern

7. Project Management Prof. dr. Heleen Riper Professor of eMental health, working at the department of Clinical Psychology of the VU University Amsterdam and the University of Leuphana in Luneburg, Germany.

Prof. dr. Jan Smit Research chair “Methodology of Longitudinal Psychiatric Research” and managing director of research and innovation at 5.InGeest, The Netherlands

Mr. Christiaan Vis, MA. Expert in European Funding, project manager and Ph.D. candidate at the department of Clinical Psychology at the VU University Amsterdam, The Netherlands

Anna van Berkel MSC Project and research assistant. Master degree in clinical psychology. Therapist in training.

Due to its complexity, appropriate management of the trial is crucial to obtain high quality data and be able to draw scientifically sound conclusions. Therefore, the Project Management Team together with the Executive Committee decided in due course to include three central trial coordinators and coordinators at the individual trial centres in the management of the project. The multi-centre trial needs specific and close attention in three distinct but related dimensions: 1) trial logistics and protocol, 2) technical platforms offering treatment, and 3) data management. Central coordinators have the task to manage, control and report on the international multi-centre trial on a central level. Local trial coordinators have the task to execute and control the local trial in every detail. The local site coordinators are responsible for all operational aspects in conducting the local trial. The central coordinators are responsible for providing the local site coordinators with relevant information and advice so they can operate the trials in line with the DoW and


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the planning. Please refer to the description of WP2 to review the practical implications of this structure.

Scientific Advisory Board A Scientific Advisory board was presented and installed at the first General Assembly. The external Advisory Board provides expert opinion and advises to the project to ensure sound execution of the project towards its goals. The persons listed in table 4 take seat in the SAB.

Table 3: Experts seated in Scientific Advisory Board

Name Affiliation Expertise Prof. dr. Per Carlbring Professor in Clinical Psychology, Internet

Interventions, Stockholm University, Sweden

Development and evaluation of eMental-health treatments for depression, anxiety and gambling

Ine van Hest, LLM

Director of the Dutch Innovation Foundation (Health Insurers NL)

Innovation in Health Care, Policy Development, Health Insurance

Prof. dr. Lee Ritterband

Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, USA

Behavioural Science, Clinical Psychology, Health Psychology

The SAB was present at the second Consortium meeting in October 2014 and critically contributed to the design of the trial, alignment of the work packages and dissemination activities. Their expenses were reimbursed by beneficiary 1.VUA in accordance with the DoW.

Communication Tools and Procedures

E-COMPARED website The E-COMPARED website provides a platform for informing stakeholders about the project and to facilitate knowledge exchange within and beyond the consortium. Two important facilities are available: 1) a publicly accessible site for informing stakeholders and those who are interested in E-COMPARED, and 2) a secured part that enables for knowledge and document exchange within the consortium. Several email lists are included as well as a dedicated and centrally managed stakeholder database that enables for efficient exchange of stakeholder information within several Work Packages. A database to keep track of the consortium’s dissemination activities is included as well.

Online repository All the documents and communications related to the E-COMPARED project are accessible for project members through the secure area at the E-COMPARED website. This space is used as document repository that contains: contracts; final official deliverables submitted to the EC; final internal deliverables; meetings (agenda, presentations, minutes); templates for the administrative and financial reporting; templates for documents (deliverables, presentations); and Contact lists.

Stakeholder database and Dissemination database Also included are a dedicated stakeholder database and a database for keeping track of the local dissemination activities. These databases are also used for the stakeholder survey in WP1 T1.2 and for shaping the synthesis activities in WP5 – synthesis. In Annex 2 an overview of all dissemination activities is provided.

E-mail and distribution lists Official communications from the Project Management Team (e.g. information requests, setting deadlines for preparation of reports, convening meeting, agendas and minutes,


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etc.) are sent by email to all participants. Contact lists are available on request at the PMT. The following mailing groups have been created and used: - [email protected]: all researchers working on the project - [email protected]: all PI’s of involved beneficiaries - [email protected]: all members of the executive committee (WP leaders) - [email protected]: project management team.

The project website is delivered by beneficiary 9.UBERN in month 3 and maintained periodically. Please refer to Deliverable D6.8 for more information. The website can be accessed at: http://1.VUA.E-COMPARED.eu/.

Contracts and binding documents The official reference documents that set out the rights and obligations of the Consortium are represented by: - The Grant Agreement (GA) signed between the EC, the Coordinator and the partners.

It defines EC grant amount, duration of the project and financing rules. It includes Description of Work (DoW) that contains the detailed description of the activities to be carried during the project.

- The Consortium Agreement (CA) signed by all the partners. It rules internal distribution of funding, project governance, voting mechanisms and IPR management.

- The Publication Policy provides consortium wide agreed guidelines on the publication of results obtained by E-COMPARED.

Reporting Research is difficult to manage due to its unpredictable nature and is therefore more activity than result driven. The key in project management is a realistic planning and clarity on responsibilities. Therefor, there are two external (to EC) reporting periods: months 1-18 and months 19-36. Besides the formal reporting to the Commission’s Services, the PMT issued two interim reports to track and document the project’s progress more accurately. The interim reviews are scheduled at month 9 and month 28. The reports covers progress, results/deliverables, justification of changes in work, planning and suggestions for changes to work plan if needed. The reporting procedures are summarized as follows: - WP leaders are required to consult their collaborators to provide the required

information (i.e. WP progress reports). - Work in progress is discussed in the monthly Executive Committee Meetings. - Partners fill-out the reporting template one month before the end of the reporting

period and are required to fill-out and sign the Form C in the EC portal. - PMT evaluates and scrambles input into one report. - The reports are made available to all consortium members and discussed within

Executive Committee and General Assembly for e.g. in deciding corrective measures.

Project meetings

Consortium Meetings Since the project teams of E-COMPARED are spread all over the EU, it has been and remains is important to organize periodic face-to-face Consortium Meetings. This gives the involved teams the opportunity to keep in contact with each other and to see and hear what work has been done, and to resolve issues. The meetings are also be used to discuss and decide at the General Assembly on important issues that arose during the execution of the project. The following E-COMPARED Consortium Meetings took place during the first reporting period.


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Table 4: Consortium meetings

Dates Venue Subject Lead partner Attendees 30/01/2014 – 31/01/2014

Amsterdam, NL at 1.VUA premises – conference centre

Kick-off including 1st General Assembly

1.VUA All beneficiary’s involved research teams

20/10/2014 – 21/10/2014

Valencia, SP at 10.UVEG premises – Fac. of Psychology

2nd Consortium meeting incl. 2nd General Assembly

1.VUA in collaboration with 6.UJI and 10.UVEG

All beneficiary’s involved research teams

Executive Committee meetings Every month of the first year and bi-monthly for the second year, the Executive Committee Meetings were held. These meetings are used for both the Project Management Team as well as all the WP Leaders to keep track of the trial preparations, execution, data analyses, modelling work and synthesizing the data. Furthermore, the alignment of WPs is discussed to ensure correct timing and expectations. The Meetings are taking place by Telephone Conference and are hosted by the PMT.

Table 5: Executive Committee meetings

Dates Venue Subject Lead partner Attendees 04/03/2014 Teleconference 1st Executive Committee meeting 1.VUA WP leaders 01/05/2014 Teleconference 2nd Executive Committee meeting 1.VUA WP leaders 05/06/2014 Teleconference 3rd Executive Committee meeting 1.VUA WP leaders 27/09/2014 Teleconference 4th Executive Committee meeting 1.VUA WP leaders 19/02/2015 Teleconference 5th Executive Committee meeting 1.VUA WP leaders 19/03/2015 Teleconference 6th Executive Committee meeting 1.VUA WP leaders 30/04/2015 Teleconference 7th Executive Committee meeting 1.VUA WP leaders 11/06/2015 Teleconference 8th Executive Committee meeting 1.VUA WP leaders Please note that we did not convene a meeting in October – January as we met at the consortium meeting in October and due to the holidays in December.

WP specific meetings The kick-off set out the first priorities for each work package. To maintain speed and ensure connectedness of the various aspects of the work packages, WP leaders initiated face-to-face meetings as well as online teleconferences and bi-lateral discussions between their collaborators and team-members. The following table provides an overview of the various face-to-face WP meetings held their subject.

Table 6: WP specific meetings

WP Dates Venue Subject Lead partner WP2 18/02/2014 Paris, FR at URC Eco,

Hotel Dieu Preparatory meeting for WP2: Clinical and cost-effectiveness of Internet-based TAU routine

1.VUA, 15.INSERM

WP4 28/03/2014 Amsterdam, NL, at 1.VUA premises – fac. of exact sciences

Initiating work on WP4: Virtual Patient Model and learning approaches

7.ULG, 1.VUA

WP3 05/05/2014 Paris, FR, at 15.INSERM premises

Initiating work on WP3: Markov modelling and systematic review

15.INSERM

WP2 20/06/2014 London, UK, at 4.LSHTM premises

Development and adaptation of the trial protocol and the technical platform in UK

1.VUA, 4.LSHTM

WP2 23/06/2014- 24/06/2014

Warsaw, PL at 11.SWPS premises

Development and adaptation of the trial protocol and the technical platform in PL

1.VUA, 11.SWPS

WP2 04/07/2014 Paris, FR at URC Eco, Hotel Dieu

Development and adaptation of the trial protocol and the technical platform in France

1.VUA, 15.INSERM

WP2, WP4

07/07/2014-08/07/2014

Amsterdam, NL, at 1.VUA premises – fac. of psychology

ICT4D developers workshop: detailing system requirements and design specificities.

7.ULG, 1.VUA


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WP2 03/10/2014 Amsterdam, NL, at 1.VUA premises – fac. of psychology

ICT4Partners met in Amsterdam for a Translation Workshop, to start input system and treatment protocol translations.

1.VUA

WP4 23/03/2015-24/03/2015

Lüneburg, GE, at 7.ULG premises

WP4 workshop: progress and next steps 7.ULG

Cooperation with other projects The PMT has sought active cooperation with the MasterMind project, which is financed under the CIP ICT-PSP program (GA. 621000). This project aims to implement and up scale evidence based eMental health in routine practice in 11 European regions. The project is lead by Region Syd Denmark (RSD), dr. Claus Duedal Pederson. Amongst others, the MasterMind project and E-COMPARED have common ground in addressing stakeholders. Additionally, data is obtained regarding the implementation costs that might provide a valuable addition to the cost-effectiveness analysis in WP3 (and vice-versa).

Financial management The PMT ensures correct and timely administering and distributing the financial contribution of the European Commission to the partners as agreed in the GA and CA.

The payment schedule is linked to the reporting periods and can be summarized as follows: - Pre-financing: 53,3% of the requested

grant after signing the contract. - 1st Financial Statement (after the

approval of the costs related to the Period 1-RP1).

- 2nd Financial Statement (after the approval of the costs related to the Period 2-RP2).

The pre-financing has been transferred to the partners as indicated in table 8. Financial Statements are paid once the reports have been submitted and validated by the Commission’s services.

Furthermore, the PMT can and has assisted and advised beneficiaries in occurring financial issues and compliance with EC regulations. To that end the PMT developed a spread sheet that is used to support the consortium partners in keeping track of their expenses and to collect the required information for the periodic and final reports. The initial budget is included and enables for critical reflection on the spending and progress towards the deliverables of the project. The reporting tools are tailor made to the specifics of each beneficiary and contains - Time sheets; - Sheets for calculating costs for consumables and travelling; - Subcontracting costs; - Realization sheet, which provides a consolidated overview of the effort, personnel

costs, costs for consumables, travel and subcontracting and relates this to the initial budget. This sheet is generated automatically;

- Explanation of Use of Resources and Activity report: Each partner is asked to provide a brief description of the activities performed during the reporting period.

- Budget: shows the initial budget that forms the basis of the budgets in the DoW.

Beneficiary Accounting date Amount (EUR) 15.INSERM 30-10-2014 305,820.17 14.Gamian 16-09-2014 28,600.00 4.LSHTM 16-09-2014 271,644.97 8.UL 16-09-2014 196,058.91 7.ULG 16-09-2014 193,255.23 3.FAU 17-03-2014 248,832.65 12.INESC 17-03-2014 143,918.41 2.LiU 17-03-2014 269,590.85 5.InGeest 17-03-2014 103,657.47 11.SPWS 17-03-2014 174,314.71 6.UJI 17-03-2014 237,545.14 10.UVEG 17-03-2014 86,104.01 9.UBERN 17-03-2014 234,654.75 Total 2,493,997.27

Table 7: Pre-financing paid to beneficiaries


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At any time, the PMT was and will remain to be available to support beneficiaries in the reporting process step by step, providing personalized assistance and advice.

Changes in the consortium After acceptance by the General Assembly, the Project Management Team started an amendment procedure mid January 2014. Following the Commission’s consent, the procedure ended successfully in June 2014. The amendment concerns the termination of beneficiary 13.UPEC’s involvement due to a transfer of dr. Karine Chevreul’s team to 15.INSERM. 15.INSERM is added as a beneficiary to the consortium and the amendment entered in to force the 1 of January 2014. All responsibilities and budget is transferred from UPEC to 15.INSERM. No pre-financing is paid to UPEC and UPEC claims no costs for this Reporting Period.

Beneficiary 12. INESC Porto changed their name in INESC TEC. The legal entity remains the same.

Changes to the legal status of the beneficiaries No changes in legal states of beneficiaries have occurred during the reporting period.

Project planning and status The project is currently in the phase of recruitment and treatment of patients and is collecting data within WP2. WP1 has finished according to the planning and WPs 4-7 are running as planned.

However, as detailed above and in the distinct descriptions of the WPs, the start of recruitment in three of the eight trial sites has been delayed substantially and recruitment falls behind the anticipated inclusion rates. Furthermore, the decision to include the DES modelling technique together with the Markov modelling in WP3 has led to an expected 4-month delay in delivering D3.4.

Problems occurred and envisaged solutions In conducting research projects like E-COMPARED, much issues arise of which some are substantial and need a resolving answer that fits the goals of the project. The following substantial issues arose and require appropriate attention: - At the start of the project, new knowledge became apparent reviewing the possibilities

of Discrete Event Simulation (DES) modelling in estimating cost-effectiveness of innovative interventions in healthcare. On the basis of this review, the WP3-team decided to include DES in the WP3 work plan. This has led to an estimated delay in the delivery of D3.4.

- Due to the complexity of a multi-centre trial like the one in E-COMPARED, the project management team issued an extension of the WP-team by including a central trial coordinator, a central technical platform coordinator, and a central database coordinator. All central coordinators have local counterparts ensuring quick and efficient communication, reporting and decision-making.

- The DoW does not detail the management of data collected in the eight trials in a central and collective manner. 5.InGeest together with 1.VUA developed a central database, data quality, data management and data issuing procedures to which all partners adhere and connect their local databases to. This solution has been developed in WP2, task 2.7.

- Learning from other trials, close monitoring of inclusion rates is important. Soon in the inclusion period the picture emerged that the inclusion rates were falling behind with the numbers that we expected to reach. The trial sites engaged in various counter measures such as including more local mental healthcare clinics, recruiting more


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therapists, informing potential patients, et cetera. Based on an elaborate set of scenarios, various solutions are proposed and currently discussed within the consortium to determine the best feasible approach. It is expected that a decisive consensus will be reached at the third consortium meeting in October 2015. Please refer to the progress report on WP2 above for more information on the possible scenarios.

- Due to the various (scientific) interest the various teams in E-COMPARED have, a detailed Publication Policy has been developed by 9.UBERN together with 1.VUA. The General Assembly accepted and acknowledged the document.

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