BJD Work package

Main project / The Low Back Pain Study
Sub project
Project leader / John Anker Zwart
Project group / The Bone and Joint Research Group, Treliske
Project type / iProject – internal / aProject – associated / cProject – collaborative
Collaborating partners / 1. (Coordinator)
Prof. John-Anker Zwart Institute of Clinical Medicine, University of Oslo
2. Prof. Jan Hartvigsen, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark
3. Ass.prof Eva Kosek Department of Clinical Neuroscience, Karolinska Institute, Stockholm
4. Prof. Aarno Palotie Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland and the Broad Institute of MIT and Harvard, Boston, USA
5. Prof. Ansgar Espeland Department of Radiology, Haukeland University Hospital and Department of Clinical Medicine, University of Bergen
6. Prof. George Peat Research Institute for Primary Care & Health Sciences, Keele University
7. Prof. Thomas Tolle Department of Neurology, Technische Universitaet Muenchen
8. Prof. Anthony Woolf The Global Alliance for Musculoskeletal Health and European Musculoskeletal Information and Surveillance Network
9. Prof. Benedicte Lie Department of Medical Genetics, Oslo University Hospital
Timeline / Expected start (2015-07) / Estimated completion (2018-12)

PROJECT DESCRIPTION (Max 1 page, full details in project plan)

Project – Aim (150 words)
The main objective of the current proposal is to uncover the underlying pathophysiological mechanisms and determine how these interact with psychological and social factors in causing recurrent and chronic LBP in order to improve preventive, diagnostic, therapeutic and preventive strategies. This objective will be addressed in eight work packages (WP), including project management (WP1), aimed at identifying novel biomarkers and disease mechanisms by combining genetic, molecular, imaging, environmental and clinical information in our unique cohorts.
·  We aim to coordinate and facilitate collaboration between top research institutions with an outstanding record in pain and low-back pain research
·  We aim to create an accessible inventory for LBP researchers worldwide of LBP phenotype data currently held within large European birth cohorts, population cohorts and biobanks, as well as clinical registries and cohorts.
·  We aim to assess, identify and validate determinants for LBP across the lifespan, identify and validate candidate physical, psychosocial and lifestyle exposures with strong main effects on LBP at different life stages and explore the effect of cumulative exposures on the occurrence and persistence of LBP and develop a prediction model based on prior cumulative exposure rather than current status.
·  We aim to assess the “biological spinal age” in LBP patients based on structural degenerative findings on MRI that are combined with systematically collected clinical information and develop clinical prediction models based on MRI phenotypes.
·  We aim to improve and develop new MRI assessment protocols of lumbar degenerative disc changes (like Modic Changes (MCs)), so that patients can be classified more consistently according to the underlying lesions and evaluate the predictive value of rapidly progressing MRI findings in adolescents in relation to development of LBP.
·  We aim to identify and characterize biomarkers for chronic LBP and lumbar disc degeneration (MCs) by assessing changes in systemic gene expression, identify cell-types and pathways involved, presence of infectious agents and whether a low-grade inflammation is reflected by an altered gene or protein expression of inflammatory biomarkers and reversed by successful treatment.
·  We aim to unravel nociceptive and neurobiological mechanisms modulating LBP and chronification by deciphering the interaction between relevant genetic variants/polymorphisms and effects on; a) altered brain activation patterns, b) pain sensitivity and modulation, and c) assess the predictive value of neurophysiological testing in a clinical setting
·  We aim to assess whether: a) patients with acute temporary, recurrent and chronic LBP have different genetic susceptibility spectra, b) assess whether genetic profiles and functional polymorphisms can predict treatment response and affect pain modulation, and c) assess the interaction between environmental and genetics susceptibility profiles
·  We aim to widely disseminate across biomedical researchers, physicians, allied health professions, health workers, patients, patient organizations, the general public, and health care decision makers, the new knowledge generated by this study on: a) how LBP best should be diagnosed by using a diagnostic tool set and biomarkers; b) how pain is generated and how this process can be blocked, alleviating the pain; c) how chronification of LBP may begin and progress, and d) how these results should be implemented in targeted treatment and preventive programs.
Objectives for Work Package 8 - Dissemination
1.  To inform the scientific community on scientific results from the Low-Back Pain project
2.  To share results from separate working packages with the overall consortium to improve coherence of the total project
3.  To inform relevant stakeholders (e.g. scientists, clinicians, patients and European policy makers) about the scientific value of the Low-Back Pain project
4.  To provide public access to all non-confidential information of the project
5.  To facilitate the use and implementation of the results in European health care practice
6.  To protect actively all newly generated knowledge with economic potential
7.  To ensure sure that all research in the Low-Back Pain Study will respect and involve gender innovation aspects
Project - Background (300 words)
Understanding health, ageing and disease: determinants, risk factors and pathways, and will focus on Low-Back-Pain.
The main objective of the current proposal is to uncover the underlying biological mechanisms and the combined effects of factors causing recurrent and chronic LBP in order to improve diagnostic, therapeutic and preventive strategies. This will be achieved by combining genetic, molecular, imaging, environmental and clinical information from existing and ongoing cohorts.
Low-back pain (LBP) is the single leading cause for disability worldwide, affects all age groups from adolescents to elderly and has increased from 58 million years lived with disability (YLDs) in 1990 to 83 million YLDs in 2010 1. The burden is accordingly substantially higher than previously assessed, in particular within the EU, causing activity limitation and work absence with subsequently enormous economic burden on individuals, families, communities, industry, health services and governments.
About 70 – 85 % of the population experience LBP during adult life. Clinical guidelines suggest that recovery from an episode of recent onset LBP is usually rapid and complete, but recent high-quality studies report that recovery is much slower and many do not recover within a year 2,3. There is good evidence to suggest that psychological constructs are significant predictors of outcomes such as more severe pain, greater functional disability, and work loss, and these constructs also play a role in the transition from acute to persistent pain and disability 4. On the other hand, biological findings like degenerative disc changes on magnetic resonance imaging (MRI) are present in more than two thirds of patients with chronic LBP (CLBP). There is, however, no reliable means for its diagnosis or treatment and the underlying biological mechanism for the transition from an acute to a chronic pain state is not known 5.
Despite considerable research efforts, LBP remains a poorly understood condition. The “biopsychosocial model” of LBP has been the standard approach over the last decades 6 and clinical guidelines promote an approach where 85-90% of patients do not receive a patho-anatomical diagnosis. The clinicians are accordingly left with a trial and error approach and are often unable to predict which patients will respond to which treatment. Since a patho-anatomic diagnosis is not pursued, clinicians apply generic symptomatic treatments such as advice to stay active and avoid bed-rest, analgesic medications, reassurance and exercises. Systematic reviews reveal that existing treatments have, at best, only small effects 7. Understanding the underlying principles of a condition is a prerequisite for designing effective interventions and preventing strategies. The biopsychosocial model has increased our knowledge of the complexity of LBP, but there is a strong need for a better understanding, in particular of the underlying biological factors, in order to improve diagnostic and therapeutic strategies as well as generate evidence based preventive measures.
It is generally recognized that the etiology of LBP is multifactorial with a complex pathogenesis. It is well known that LBP is associated with several negative determinants of health and that there are individual differences in pain perception, but too little is known about the interaction between environmental, biological and genetic factors. The absence of a good understanding of the underlying biological causes for why LBP becomes chronic has hampered the development of effective prevention and treatment.
In acknowledgement of the huge burden and impact of musculoskeletal disorders in Norway as well as globally, the National Co-operation Group on Health Research (NSG) endorsed in 2012 a national effort to focus on research within the field of musculoskeletal disease (www.muss.no), and The European Parliament has recently signalled that research on rheumatic and musculoskeletal conditions shall be among the areas prioritized within the EU Research Framework Programme for 2014 to 2020 (Horizon 2020).
Project – Plan (400 words (target audience, population, methods , feasibility etc)
Description of work (where appropriate, broken down into tasks), lead partner and role of participants
The Low-Back Pain consortium will ensure optimal dissemination and exploitation of knowledge to stakeholders.
Six tasks with associated sub-tasks have been identified:
Task 8.1 Set up a Low Back Pain website (Deliverable 8.1 - Delivery of The Low-Back Pain project website (MO 6)
1. The WP8 lead produce an initial design for a Low-Back-Pain website that will be partly open to the general public with an intranet-restricted part designated for internal communication between participants and external communication to the EU. The WP8 lead will agree the initial design with the WP1 lead.
2. The WP8 lead and the WP1 lead will agree and identify the appropriate resources that are qualified to build and deliver the Low-Back-Pain website.
3. The WP8 lead and the WP1 lead will provide the identified resources with the required design to develop and deliver the Low-Back-Pain website.
4. The WP8 lead will maintain the content of the website in line with the Dissemination Plan throughout the life of the Low-Back Pain project. The Low-Back Pain website will be accessible by links from other websites, including those of the member organisations of the consortium and those of the Global Alliance for Musculoskeletal Health – the Bone and Joint Decade.
5. Beyond the project end, the website will continue to be accessible from the linked sites to sustain dissemination of the results.
Task 8.2 Identify the Stakeholder Map (Deliverable 8.2 – Stakeholder Map (MO 3)
1. The WP8 lead will contact the member organisations of the consortium who will be responsible for providing stakeholder details based on specified criteria.
2. The WP8 lead will combine the lists received and will draw up one list – the draft Stakeholder map. The list will be circulated among all the member organisations of the consortium to reach consensus.
3. The stakeholder map will be placed on the LBP web site in the area confidential to members of the consortium, and will be regularly updated by the WP8 lead during the life span of the study.
Task 8.3 Prepare and Publish Newsletter (Deliverable 8.3 - Regular newsletters (every 6 Mo)
1. The WP8 lead will collate information about the achievements of the study, including reports, published articles and press releases, presentations and media appearances by its members and will also collate details of relevant events scheduled throughout the life of the LBP study.
2. The WP8 lead will prepare and publish an internal newsletter every 6 months. The newsletter will be circulated among all the member organisations of the consortium.
3. The WP8 lead will prepare and publish interim newsflash items on the LBP website to keep members of the consortium informed of progress and dissemination achievements.
Task 8.4 Maintain schedule of Scientific Meetings (Deliverable 8.4 – Schedule of Scientific Meetings (every 3 Mo)
1. The WP8 lead will contact the member organisations of the consortium and ask for details of scientific meetings / conferences relevant to dissemination of the LBP results.
2. The WP8 lead will collate the information received and draw up a schedule of events. The schedule of events will be circulated among all the member organisations of the consortium to reach consensus.
3. The WP8 lead will contact the organisers of scientific meetings and get details of the criteria and timescales for preparing and presenting abstracts and posters and for being invited to present.
4. The schedule of Scientific Meetings and criteria and timescales will be placed on the project web site and will be regularly updated by the WP8 lead during the life span of the study.
Task 8.5 Dissemination of Scientific Articles and Press Releases; record of achievements (Deliverable 8.5 - List of all published Low-Back Pain scientific papers and press coverage (MO 36)
1. Each of the member organisations of the consortium will prepare papers of the outcomes of the study for publication in scientific journals as required by the WP1 Lead.
2. The WP8 Lead will be informed of publication plans and will collate finalised papers.
3. The WP8 lead will disseminate the papers to other members of the consortium and to external stakeholders as agreed by the WP1 Lead.
4. Each of the member organisations of the consortium will inform the WP8 lead of opportunities for press releases and the open access media that is being targeted.
5. The WP8 lead will prepare and distribute press releases for review and consensus approval by the member organisations of the consortium.
6. The WP8 lead will distribute the agreed press release to the open access journals, as identified.
7. The WP8 Lead maintain a record of dissemination achievements that will include the presentations, posters, media appearances and other dissemination achievements of the Low-Back-Pain study, as advised by each of the member organisations of the consortium.
8. The WP8 lead will publish the record in the six monthly newsletter and on the LBP website.
Task 8.6 Prepare Dissemination Plan (Deliverable 8.6 – Dissemination plan (MO 36)
1. The WP8 lead will draft a dissemination plan in conjunction with the WP1 lead which will include: the overall dissemination strategy, the map of the stakeholders, the criteria for research to respect and involve gender innovation aspects, the terms of reference for an IPR task force that guarantees that Low-Back Pain data is adequately protected.