Work Package 1: Health care interventions (HCI)
In this work package (WP) current health care interventions have been evaluated, using both established core outcome sets (COS) and COS that are newly developed within the MDS-RIGHT project. Health care use and associated health care costs have been quantified and evaluated. National policies regarding pharmacological treatment options for MDS have been evaluated as to their cost-effectiveness. Data from WP2, 3 and 4 has been used to stimulate personalised medicine, e.g., to identify which health care intervention works best for which patient, based on clinical and (epi)genetic information. The outcomes of this WP contribute to better clinical and regulatory decisions, which lead to reduction of overtreatment (and therefore more efficient use of health care resources), effective patient management, evidence based therapy use and healthier ageing.
Partners in this work package
- University of York
- Groupe Francophone des Myélodysplasies
- Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Deliverables
- D1.1: Interim core dataset for model development and report on detailed statistical analysis plan.
- D1.2: Preliminary analyses of clinical and cost effectiveness data based on D1.1.
- D1.3: Final dataset incorporating data generated from WP2, WP3 and WP4.
- D1.4: Updated models of D1.2 and generation of new core outcome sets incorporating data generated from WP2, WP3 and WP4.
- D1.5: Final analyses of models and data from D1.3 to produce output to feed into WP5 and WP6.
- D1.6: Final report of WP1 and preparation of manuscripts.
Work Package 2: Diagnostics and bioinformatics
The improvement of diagnostic procedures has been an important driver of this WP. Up to now bone marrow biopsies are still required to diagnose MDS. This procedure is invasive and demanding. Besides that, existing techniques of BM examination are not always diagnostic of MDS in subgroups of patients. The application of less invasive new molecular methods using peripheral blood and flow cytometry within the elderly AoE population has been explored and compared to bone marrow biopsies. In addition, genetic research has been performed. Genome-wide methylation patterns of 500 patients have been and continue to be studied and related to genetic mutational analyses. Also, a large set of clinical, biological and quality of life data has been integrated, to assess the added diagnostic, prognostic and predictive value of the individual techniques used in WP2. The work in WP2 contributes to new and improved diagnostic methods and to individualized therapeutic choices.
Deliverables
- D2.1: Periodic reports on mutational sequencing and epigenetic profiling in various cohorts.
- D2.2: Periodic reports on immunophenotyping in various cohorts.
- D2.3: Reports on ms data comparing 100 blood samples with 100 paired bone marrow samples.
- D2.4: Periodic report on bioinformatic integration of data.
Work Package 3: Health-related quality of life issues in elderly patients with anaemia
Health related quality of life (HRQoL) is an important indicator of treatment efficacy. To correctly assess HRQoL, a new questionnaire (QUALMS-1) has been implemented and is currently being validated. Electronic and patient friendly versions were implemented to improve patient compliance to complete these type of questionnaires. Items and domains from HRQoL instruments considered relevant by patients have been identified and combined with existing core outcome sets (COS; WP1) to create new COS. Predictors for low HRQoL have been identified. HRQoL has been used to evaluate the effect of different treatment regimes on the different and newly identified subtypes (WP2) of MDS. Overall, the measures of HRQoL have been used for effect measurement of health care interventions and to evaluate the cost-effectiveness of interventions stratified for subgroups.
Deliverables
- D3.1: A specific HRQoL questionnaire for MDS patients (QUALMS-1) validated in a large population of European MDS patients.
- D3.2: A new treatment outcome set including patient reported, disease specific outcomes.
- D3.3: Report of new predictors and prediction functions for impaired HRQoL.
- D3.4: A list of HRQoL adapted treatments for each biologic MDS-subtype.
- D3.5: Causal diagram with a description of direct and indirect effect estimates for different health-care interventions on HRQoL.
- D3.6: Report on the newly defined burden of MDS on HRQoL by comparison with non-MDS matched reference cohorts.
- D3.7: A set of measures and prediction functions of HRQoL.
Work Package 4: Outcome prediction
The aim of this work package was to improve the tailoring of interventions to the individual patient. Therefore, new and better treatment-outcome prediction models are being developed for use in clinical practice. Molecular defects with prognostic value identified in WP2 are being integrated in these models. Statistical techniques have been used to identify new biological subgroups of MDS with specific biological pathways that might be good candidates for the development of targeted therapies. Data from WP2 has been used to identify if molecular defects associated with MDS exist in elderly patients with unexplained anaemia. This enables better diagnosis of anaemia and use of therapeutic clinical interventions proven to be effective in MDS treatment.
Deliverables
- D4.1: Report describing prognostic impact of newly defined individual genetic defects and groups of associated genetic defects on response to the existing health care interventions (HCI) (together with WP1).
- D4.2: List of newly identified genetic defects which support development of novel drugs.
- D4.3: Report of early treatment response indicators supporting a targeted use of existing HCI.
- D4.4: Report of new specific genetic signatures which support minimal diagnostic criteria recognizing MDS in older individuals with anaemia, and guiding appropriate treatment.
- D4.5: Report on newly generated, high-quality health economic evidence of benefit arising from implementation of personalised MDS care strategies.
Work Package 5: Guideline development
Existing guidelines were mainly based on expert opinions and retrospective observational data in selected patient groups. The European guidelines published in 2013 by the European LeukemiaNet (ELN) has been evaluated and updated in close co-operation with both European and non-European MDS-experts. In parallel, new and evidence-based guidelines have been developed, based on newly identified prognostic subgroups within MDS-RIGHT as well as newly published evidence. The new evidence-based guidelines are interactive web-based and publicly available in the 'Patient management' section of the European MDS competence network website (www.mds-europe.org). The interactive guideline algorithms have been developed to allow professional health care providers to enter individual patient data and obtain advice for individual patients based on existing and newly defined dynamic prognostic response parameters. The European MDS competence network developed in WP6, serves as a platform for providing up-to-date, evidence-based information and regulatory guidance to health care providers.
Deliverables
- D5.1: Approved European and international guidelines uploaded at new ELN-linked website.
- D5.2: Yearly electronic updates of the evidence-based therapeutic guidelines based on the ongoing analyses of MDS-RIGHT (WP1-4) and consensus within the Steering Committee.
- D5.3: Report of socio-economical aspects of the elderly low risk MDS population.
- D5.4: Scientific report describing the flexible electronic web-based system with permanently updated evidence-based guidelines for MDS treatment.
- D5.5: Report on the endorsement of the new evidence-based guidelines for MDS patients in all institutes of the MDS-RIGHT consortium and for MDS patients outside the MDS-RIGHT institutions.
- D5.6: Updated patient handbooks of the national MDS patient groups containing relevant information on the MDS-RIGHT guidelines.
- D5.7: Panel methodology and annual panel meetings.
Work package 6: Dissemination, exploitation and communication
All new findings on health care interventions, HRQoL, new diagnostic tools, new treatment-outcome prediction models and new guidelines have to find their way to the health care providers treating MDS-patients. This was (and continues to be) the ultimate goal of WP6, in which a European MDS competence network and a platform/website for communication with stakeholders has been developed. The MDS competence network closely collaborates with the national MDS patient groups in Europe and the international MDS Foundation. The stakeholder network serves as an easily accessible information source for both patients and professionals, as a platform for discussion and as a lobby organisation for MDS-patients towards other stakeholders. Stakeholders and end-users have been continuously involved in WP6 to increase acceptance and compliance with treatment. The organisation of workshops and conferences, participation in exhibitions, scientific publications and PR activities have also been an important aspect of this WP.
Deliverables
- D6.1: Report of dissemination plan.
- D6.2: Discussion platforms and a common website for stakeholder interaction.
- D6.3: Completed catalogue of all MDS caregiver cooperative groups patient support groups and existing documents (written, website) in participating countries.
- D6.4: Yearly MDS Stakeholders Newsletters.
- D6.5: Report on the participation in international patient support group meetings.
- D6.6: Report on two meetings with physicians (professional stakeholders) to inform about state-of-the-art in the field of MDS.
- D6.7: Yearly updates of MDS website.
- D6.8: Promotion of educational and scientific meetings, pocket cards, posters, flyers, exhibition booth for meetings.
Work Package 7: Project management and consortium
This WP mainly consisted of managing, monitoring and coordinating the different WPs and other aspects of MDS-RIGHT. Besides this, the organisation of project and project related meetings and the reporting to, and liaising with, the European Commission (EC) were important parts of WP7.
Deliverables
- D7.1: To manage and monitor a large prospective, longitudinal, observational European-wide study on current health care interventions for elderly patients with lower-risk MDS.
- D7.2: To manage implementation of new technological diagnostic methodologies.
- D7.3: To manage implementation of new COS in the established HCI.
- D7.4: To monitor, track and control deviations due to progress, costs, financial and scheduling changes.
- D7.5: To ensure that the required reporting is prepared and delivered in a timely manner according to quality assurance standards and homogeneity.