A Programme for ALS Care in Europe (ALS-CarE)

Lead Research Organisation: King's College London
Department Name: Clinical Neuroscience

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that strikes in the prime of life. There are currently no effective disease modifying therapies for ALS and death usually occurs within 3 years of symptom onset. Management is palliative and is aimed at maximising quality of life and minimising the burden of disease. The complexity and rapidly progressive nature of ALS requires a responsive multidisciplinary care system that that is built on reliable disease staging and evidence based symptom management.

The purpose of ALS-CarE is to incorporate detailed clinical information drawn from population based sources into a responsive care programme. A standardised staging system will be validated, and quality of life and patient experiences will be measured and management optimised across disease stages from diagnosis to end of life. Health economic analysis will identify key differences in resource utilisation and will be useful for pharmaco-economic analyses of new therapeutics. The completed project will provide a user-friendly best practice framework for ALS that can be modified for management of other neurodegenerative diseases.

Planned Impact

For an Impact Summary relating to societal and economic impacts, please see the attached document "Pathways to Impact". This is a summary of the Academic Impact.

Although our partners come from six countries with very different health care systems and different cultures, all are members of a highly successful European ALS Consortium (ENCALS), with extensive existing collaborations in basic, translational and clinical aspects of ALS. The strength of this application, underpinned by our collective experience as key European ALS clinician scientists and healthcare researchers, gives us a unique opportunity to study and learn, both from the common elements and the differences between our systems and our services. The benefits of this proposal are further enhanced by existing support provided by the Health Research Board in Ireland to ALS-CarE Partner 1 (Dublin). Thanks to the work already undertaken within this three-year project, much of the infrastructure and methodological approaches needed for ALS-CarE are currently under development and will be readily available to the ALS-CarE consortium at the start of the project, thus expediting the research programme. The outcome will provide an expert-led evidence-based and user-friendly protocol for management of ALS in Europe that can also operate as a guide and
educational tool for non-specialist services and voluntary groups providing care for ALS. Moreover, on completion, the entire programme will be available for adaptation to other neurodegenerative conditions such as Alzheimer's Disease, Parkinson's Disease and frontotemporal dementia.

In order to establish a metric by which care can be measured from a health economic perspective, a strong focus will be placed on the components of the care matrix that are considered most useful by the users (patients and families). This will be achieved by integrating the outcome of a qualitative project currently funded by the Irish Health Research Board to examine user attitudes towards ALS care with the care matrix. As part of this process, patients and carers, (including international stakeholder organizations such as PatientslikeMe http://www.patientslikeme.com/research) will be provided with an opportunity to comment extensively on the usefulness of the care programme, yielding qualitative data that will be analysed to identify core themes that can be incorporated into existing and novel health economic tools.

ALS-CarE will seek regular advice through the Executive Board from eminent Health Services Researchers and Health Economists assembled in the Scientific Advisory Board (SAB) and stakeholders in the Stakeholder Platform. The SAB will provide expert advice on the content, quality of the deliverables, ethical issues, general philosophy and direction of the project, corrective measures in the content of the work if necessary and the dissemination and exploitation of project results. The SAB will be chaired by Dr. Brian Dickie from MNDA. The Consortium has obtained full commitment from ALS patient organisations from all participating countries.

Knowledge exchange within the consortium will be facilitated by yearly consortium meetings and an exchange program. Once every year a consortium meeting will be organised. During this meeting all the partners will discuss the project progress and will exchange other relevant knowledge in their field. For the last consortium meeting representatives of all national funding agencies and policy bodies will be invited to share the final results of the project. The ALSCarE consortium acknowledges that training of young researchers and mobility within the consortium will be beneficial for maximal knowledge transfer. Therefore, all consortium partners will exchange three of their (PhD) students and/or postdoctoral researchers for 2 - 4 months during the duration of this project. The aim will be to exchange knowledge of the main research techniques between different consortium members.

Publications

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Agosta F (2015) The El Escorial criteria: strengths and weaknesses. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Al Khleifat A (2019) Telomere length is greater in ALS than in controls: a whole genome sequencing study. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Aragones JM (2016) Amyotrophic lateral sclerosis: A higher than expected incidence in people over 80 years of age. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Balendra R (2019) A standard operating procedure for King's ALS clinical staging. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Balendra R (2014) Estimating clinical stage of amyotrophic lateral sclerosis from the ALS Functional Rating Scale. in Amyotrophic lateral sclerosis & frontotemporal degeneration

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Balendra R (2015) Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials. in Journal of neurology, neurosurgery, and psychiatry

 
Title YouTube educational video on ALS 
Description Educational video on ALS research available on YouTube 
Type Of Art Film/Video/Animation 
Year Produced 2018 
Impact Patient information and understanding about ALS and research 
URL https://www.youtube.com/watch?v=7KVSbwe7bHo
 
Description An analysis of survival by symptom burden in ALS showed that disease burden confined to a neurological segment is associated with a worse prognosis than more diffuse disease. Quantitative and qualitative analyses of the factors influencing patient decision-making at different clinical stages emphasize the need for a precision medicine, individualised approach. Clinical staging has been applied retrospectively to two clinical trial datasets, showing that clinical stage has a role in clinical trial design. A combined staging system has been proposed incorporating both the Kings Clinical Staging System and the MiTOS Staging System to more meaningfully represent the illness throughout its complete course. Factors influencing decision making for gastrostomy and non-invasive ventilation show that person, care-giver and clinician-centred factors interact in a complex way requiring multi-professional input and a personalised approach to care. The patient's evaluation of quality of life, the desirability of prolonging life, and acceptance of the disease and its progression by both patient and caregiver were the most important factors in decision making about gastrostomy or non-invasive ventilation. A mapping review of international guidance on the management and care of ALS found that certain domains in ALS care, mainly disease-specific domains such as breathing and swallowing, are extensively addressed in the literature whereas other subjects, such as care coordination, receive little attention. This mapping review provides a scientific basis for targeting and developing the clinical content of a quality improvement intervention for the management of ALS. In an analysis of the clinical characteristics and palliative approaches in ALS patients a low ALSFRS-R, high incidence of ophthalmoplegia and extended ventilator dependency were found before withdrawing from long-term ventilation (WLTV). The key finding was that the presence or absence of ventilator-free tolerance determined the approach to the management of symptoms, the setting for immediate end-of-life care and the course of dying in WLTV.

Clinical staging is now being included as an end-point in ALS clinical trials and in international consensus guidelines for ALS.
Exploitation Route These findings can be used by pharmaceutical industry to inform clinical trial design, by multidisciplinary health care teams to inform care given to patients, how information should be given to patients, caregivers and health professionals, and palliative care and communication specialists in understanding communication needs and other interventions at end of life. In addition, new technologies for communication for example, need to be developed. These outcomes are the result of our findings in understanding phenotypic presentations and their relationship to the disease journey, our findings on clinical staging, our findings on understanding decision making factors, and our findings on end of life changes and interventions.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We developed an ALS staging system which is being refined within the ALS-CarE programme and applied within the STRENGTH programme. ALS Staging systems have been used for harmonised clinical trials training across Europe, for analysis of the timing of cognitive change in ALS, and for consultancy and advisory work for multiple pharmaceutical companies. The staging systems are now included as endpoints in commercial clinical trials and in international consensus ALS guidelines.
First Year Of Impact 2015
Sector Healthcare
Impact Types Economic,Policy & public services

 
Description Advisory Committee for large pharmaceutical company
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
Impact A new drug for ALS is now available, an outcome influenced by this advisory panel. The drug influences quality of life.
 
Description Advisory committee for a small pharmaceutical company
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
 
Description Airlie House ALS Clinical Trials Guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact This was an international consultation on best practice for clinical trials in ALS, facilitated through a Delphi process. The best practice guidelines are still in review but almost finalized.
 
Description Association of British Neurologists Genetics Advisory Committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Guideline Title Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry
Description Citation of ALS clinical staging in FDA guidelines for clinical trials
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Recommendation for commercial and academic-led trials in ALS to consider disease stage for inclusion and outcome
URL https://www.regulations.gov/document?D=FDA-2013-N-0035-0973
 
Description Guidelines for pain management in MND/ALS
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact As a result of a study of pain in MND/ALS, we have published advice for patients and for health care professionals for the management of pain, and this has been adopted by the patient organisation, the Motor Neurone Disease Association
URL https://www.mndassociation.org/forprofessionals/mndmanagement/pain/
 
Description Influencing government policy on Continuing HealthCare (CHC)
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Guideline Title Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials
Description King's Clinical ALS Staging
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact The clinical staging system is now recommended for ALS clinical trials, and is required by the FDA for future trials.
 
Guideline Title Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials
Description King's clinical staging - in consensus guidelines for clinical trials in ALS
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
URL https://n.neurology.org/content/neurology/early/2019/03/08/WNL.0000000000007242.full.pdf
 
Description Staging for clinical practice and clinical trials
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact The influence is a clinical staging system for ALS. This has been used by 12 European countries, all trained in assessment and certified. It has also been used for research and clinical practice in at least one US ALS clinic.
 
Description Standard operating procedure for King's ALS clinical staging
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact King's ALS clinical staging is now widely used in clinical practice and in clinical trials and other clinical research. This standard operating procedure ensures practice is uniform worldwide.
URL https://www.ncbi.nlm.nih.gov/pubmed/30773950
 
Description Standardised method for application of ALSFRS-R
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact The ALSFRS-R is a rating scale for assessing function in ALS. The influence is a standardised method for application of the ALSFRS-R, trained and certified across 12 European countries, ensuring standardised assessment and harmonised outcomes.
 
Description Timing of Riluzole use by clinical stage of ALS
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact We showed that Riluzole extends the last stages of life with ALS. It has since also been shown that it extends the very early stages too by replicating our methods applied to a different dataset. These findings have impact on the advice given to patients, and mean that RIluzole should be started early, but also its use in late stage needs discussion with the patient, since it will simply extend life at a stage where health related quality of life is poor.
URL https://www.ncbi.nlm.nih.gov/pubmed/29525492
 
Description JPND ALS-CarE
Amount £78,400 (GBP)
Organisation JPND Research 
Sector Academic/University
Country Global
Start 02/2014 
End 01/2017
 
Description MNDA Project Grant (The UK National MND Registry)
Amount £277,101 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2019
 
Description NIHR Healthcare
Amount £9,237 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2014 
End 09/2017
 
Description Programme Grant (MIROCALS)
Amount £387,723 (GBP)
Funding ID 633413 
Organisation European Commission 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start 09/2015 
End 08/2019
 
Description Research Grant (ALSoD)
Amount £40,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 01/2020
 
Description Research Grant (ALSoD)
Amount £102,469 (GBP)
Organisation ALS Association 
Sector Charity/Non Profit
Country United States
Start 02/2017 
End 01/2020
 
Description Research Grant (ATXN2 penetrance)
Amount £134,207 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2015 
End 08/2019
 
Description Research Grant (Bioinformatics)
Amount £171,749 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description Research Grant (COMMEND)
Amount £1,373,735 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 12/2012 
End 05/2022
 
Description Research Grant (JPND BRAIN-MEND)
Amount £2,044,052 (GBP)
Funding ID MR/R024804/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2021
 
Description Research Grant Fellowship
Amount £265,000 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2016 
End 02/2019
 
Description Research Grant Studentship
Amount £95,574 (GBP)
Organisation Motor Neurone Disease Association (MND) 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2018 
End 06/2021
 
Title ENCALS Survival Model for ALS 
Description This mathematical tool allows a personalized survival prediction for patients. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact The tool allows a personalized survival prediction for any individual patient. This is used in clinic by neurologists to counsel patients, but is particularly useful for the design of clinical trials, and is now being used as an inclusion criterion in trials. 
URL http://encalssurvivalmodel.org/
 
Title King's Clinical Staging for ALS 
Description King's Clinical Staging is a system for describing ALS disease stage using simple clinical parameters. It was first published in 2012, but as a result of the award ALS-CarE, has been developed further, validated, used by multiple other research groups, and implemented into clinical practice internationally. It has also been used and developed for analysis of genetic outcomes in the award STRENGTH. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2014 
Provided To Others? Yes  
Impact 1. Multiple other research groups have used this method for analysis (eg Association between estimated total daily energy expenditure and stage of amyotrophic lateral sclerosis. Lee J et al. Nutrition. 2017 Jan;33:181-186. PMID: 27544003; Amyotrophic lateral sclerosis: a comparison of two staging systems in a population-based study. Ferraro D et al. Eur J Neurol. 2016 Sep;23(9):1426-32. PMID: 27238551; Neuropsychological assessment in different King's clinical stages of amyotrophic lateral sclerosis. Trojsi F et al. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(3-4):228-35. PMID: 26905940 and others). 2. Several pharmaceutical companies have started to use the method as an outcome measure in clinical trials for ALS 3. An academic led clinical trial is using ALS staging as an outcome measure 4. ALS Staging is now included as a formal outcome measure in international consensus guidelines from the World Federation of Neurology (see section 3 in URL below) 
URL https://www.rarediseasesnetwork.org/cms/Portals/5/Final%20Draft%20of%20ALS%20CT%20Guidelines%20for%2...
 
Title Latent class cluster analysis 
Description Patients are stratified into clinical subgroups based on latent class cluster analysis of variables ascertained at first clinic visit. This strongly predicts survival, may predict genetic subgroups and can be replicated in multiple populations 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2015 
Provided To Others? Yes  
Impact This method is now used across European ALS research groups to stratify patients for research, and is being studied in two different programme grants as a stratification method. 
 
Title Multistage model of ALS 
Description We have applied a model derived from the cancer field to neurodegeneration. We have shown that ALS is a 6-step process rather than a dose-dependent process. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2014 
Provided To Others? Yes  
Impact This represents a large change in the prevailing disease model and will allow new approaches for identification of risk factors and prevention strategies. 
URL http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70219-4/fulltext
 
Title Standard Operating Procedure for King's ALS Clinical Staging 
Description Clinical staging method for people with ALS. The King's system is now widely used internationally in clinic, research and clinical trials. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? Yes  
Impact Clinical trial design now incorporates King's staging to understand the timing of treatment benefit, for analysis as an outcome measure, and for health economics analysis. 
URL https://www.ncbi.nlm.nih.gov/pubmed/30773950
 
Title Latent Class Cluster Analyses (LCCA) 
Description A latent class cluster analyses is a latent variable model where the latent variable is a categorical variable with k possible latent classes and the observed items are either categorical or continuous. It is used to classify ALS patients on the basis of the described variables into symptom clusters. In our study the cluster solution needs to be controlled for country. This is done by multi-group latent cluster modelling, which compares the structure of measurement models across groups (in this case: countries) and allows to control for differences between countries. It is similar to factorial invariance assessment in factor analyses. Multi-group latent class cluster analyses were performed by including "country" as a categorical predictor variable of the latent class in the model (Kuha 2013). 
Type Of Material Computer model/algorithm 
Year Produced 2015 
Provided To Others? Yes  
Impact For each cluster solution the measurement model equivalence with latent cluster probabilities varying between countries (proportion of clusters can differ between countries) but the same measurement model between countries (the relationship between items and latent variables is the same between countries) fits data best. After selecting the specification of the multi-group latent variable model the number of classes was determined by comparing goodness of fit measures. Figure 2 shows the information criteria (smaller is better model) for the different number of clusters. It can be seen that information criteria decrease with increasing number of clusters but decrease slows down after 4 to 5 clusters. After 5 clusters, clusters split in smaller ones or new clusters become extremely small. We therefore decided to select the 5 cluster solution which is similar to the previous studies. The entropy of the selected model was very good (0.95). 
 
Title National MND Register 
Description A national population register capturing every case of ALS in the UK with clinical information 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact The database will be used as the basis of a funded research programme, AMBROSIA, designed to identify biomarkers for ALS 
 
Title Project MinE databrowser 
Description Summary statistics and output from the Project MinE whole genome sequencing consortium 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Increased ability for researchers to identify ALS genes or interpret their own findings. Increased collaboration. 
URL http://databrowser.projectmine.com/
 
Title Survival prediction model for ALS 
Description A comprehensive survival prediction tool for ALS 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? Yes  
Impact Use of the model by pharmaceutical company analyzing clinical trial data 
URL http://encalssurvivalmodel.org/
 
Description ALS-CarE 
Organisation Trinity College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution Epidemiology, cognitive and phenotyping data
Collaborator Contribution Epidemiology, cognitive and phenotyping expertise, as well as qualitative expertise
Impact See form under publications. Multidisciplinary including health services research, environmental studies and phenotyping.
Start Year 2014
 
Description BRAIN-MEND 
Organisation EU Joint Programme - Neurodegenerative Disease Research (JPND)
Country European Union (EU) 
Sector Public 
PI Contribution Coordinator. Samples, expertise, data, infrastructure
Collaborator Contribution Samples, expertise, data, infrastructure
Impact None yet
Start Year 2018
 
Description MIROCALS consortium 
Organisation Brighton and Sussex University Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution We have helped design the project, recruited patients to a clinical trial, and we are now performing whole genome sequencing on the samples to determine responder genotypes
Collaborator Contribution Setup of the study, recruitment of patients, basic science research in RNA and immunology
Impact Publications: https://www.tandfonline.com/doi/full/10.1080/21678421.2018.1562553 https://www.tandfonline.com/doi/full/10.1080/21678421.2017.1349151 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558284/ https://link.springer.com/article/10.1186/s40478-019-0724-4 https://eprints.soton.ac.uk/430197/1/Telomere_length_is_greater_in_ALS_than_in_controls_a_whole_genome_sequencing_study.pdf
Start Year 2015
 
Description MIROCALS consortium 
Organisation Pitié-Salpêtrière Hospital
Country France 
Sector Hospitals 
PI Contribution We have helped design the project, recruited patients to a clinical trial, and we are now performing whole genome sequencing on the samples to determine responder genotypes
Collaborator Contribution Setup of the study, recruitment of patients, basic science research in RNA and immunology
Impact Publications: https://www.tandfonline.com/doi/full/10.1080/21678421.2018.1562553 https://www.tandfonline.com/doi/full/10.1080/21678421.2017.1349151 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558284/ https://link.springer.com/article/10.1186/s40478-019-0724-4 https://eprints.soton.ac.uk/430197/1/Telomere_length_is_greater_in_ALS_than_in_controls_a_whole_genome_sequencing_study.pdf
Start Year 2015
 
Description Project MinE 
Organisation Trinity College Dublin
Department Neurology
Country Ireland 
Sector Academic/University 
PI Contribution This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding
Collaborator Contribution The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com
Impact Various genetics papers listed under STRENGTH programme
Start Year 2014
 
Description Project MinE 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding
Collaborator Contribution The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com
Impact Various genetics papers listed under STRENGTH programme
Start Year 2014
 
Description Project MinE 
Organisation University of Massachusetts
Department University of Massachusetts Medical School
Country United States 
Sector Academic/University 
PI Contribution This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding
Collaborator Contribution The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com
Impact Various genetics papers listed under STRENGTH programme
Start Year 2014
 
Description STRENGTH 
Organisation Cantonal Hospital St. Gallen
Country Switzerland 
Sector Hospitals 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Catholic University of Louvain
Country Belgium 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation National Institute of Health and Medical Research (INSERM)
Department Nimes (INSERM)
Country France 
Sector Public 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation Trinity College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Leuven
Department laboratory for cognitive neurology
Country Belgium 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Sheffield
Department Sheffield Institute for Translational Neuroscience (SITraN)
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Turin
Country Italy 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description STRENGTH 
Organisation University of Ulm
Country Germany 
Sector Academic/University 
PI Contribution This is a JPND Consortium for which I am coordinator
Collaborator Contribution We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise.
Impact Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics
Start Year 2014
 
Description TRICALS 
Organisation ENCALS
Country Netherlands 
Sector Private 
PI Contribution Expertise in setting up a Europe wide clinical trials consortium. Training of staff in King's clinical ALS staging
Collaborator Contribution Access to data from large pan-European population ALS registers. Expertise in setting up a clinical trials consortium
Impact Training programme for TRICALS at https://www.encals.eu/meetings/tricals-workshop/
Start Year 2016
 
Title Lighthouse Trial 
Description Phase 2 trial of Triumeq in ALS now complete and published. Seeking Phase 3 start. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2019
Development Status Actively seeking support
Clinical Trial? Yes
Impact Increased collaboration internationally on ALS clinical trials 
URL https://www.tandfonline.com/doi/full/10.1080/21678421.2019.1632899
 
Title Lithium PRELUDE trial 
Description We have shown that Lithium carbonate, while ineffective in ALS as a whole, is effective in people with a poor prognosis genetic variant in the UNC13A gene (homozygosity for the CC genotype). We are now seeking funding for a trial of lithium in patients with ALS who carry this poor prognosis variant. This will be a precision medicine approach in ALS. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact The initial findings have been published, and if the trial confirms the analysis, this will become a new treatment for ALS. 
URL https://www.ncbi.nlm.nih.gov/pubmed/28978660
 
Title MIROCALS 
Description A clinical trial of low-dose interleukin-2 for amyotrophic lateral sclerosis, currently in a Phase 2 clinical trial, funded by Horizon 2020 and the MND Association 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2015
Development Status Under active development/distribution
Impact The trial includes an assessment of Riluzole therapy, the first of its kind 
URL http://www.mirocals.eu/en/
 
Title Survival model for ALS 
Description A tool for predicting survival in ALS 
Type Of Technology Webtool/Application 
Year Produced 2018 
Impact Use of the prediction tool for analysis of clinical trial phase 2 data 
URL http://www.encalssurvivalmodel.org
 
Title Unique global ID for ALS research 
Description We have developed a tool to convert clinical information into a unique global ID using SHA2 encryption. The method allows sharing of IDs between research groups to identify duplicates or match participants, without breaking anonymisation. It uses a salt to protect against brute force breaking of anonymity. 
Type Of Technology Webtool/Application 
Year Produced 2016 
Impact This method is now being used across Europe in several studies including ALS-CarE, STRENGTH, the UK National MND Register and others, including retrospective application of the system to previous studies such as LiCALS and the UK MND DNA Bank, allowing further analyses to take place. 
 
Description 25th International Symposium on ALS/MND (Brussels) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact At the International Symposium on ALS/MND this year over 800 people came together to hear the latest research findings.
The 26th annual event was a truly international affair, with scientists and health professionals from over 30 countries attending. The clinical trials session was a great example of this and featured presentations from Japanese, American and South Korean researchers.
Everyone who attended the Symposium was encouraged by the biomedical and care research that was discussed, including interesting conversations on how we classify MND, and how MND originates and spreads from one part of the body to another. There was a particularly thought provoking session on the way neurologists communicate a diagnosis of MND, put very eloquently by Juliet Jacobsen as 'delivering the horrible information in a hopeful way'.
Year(s) Of Engagement Activity 2014
URL http://www.mndassociation.org/research/international-symposium/
 
Description 26th International Symposium on ALS/MND (Orlando) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The symposium is the largest medical and scientific conference specific to MND and is the premier event in the MND research calendar for discussion on the latest advances in research and clinical management.

Each year, the symposium attracts over 800 delegates, representing the energy and dynamism of the global MND research community.
Year(s) Of Engagement Activity 2015
URL http://www.encals.eu/past-meeting/encals-satellite-meeting-2015-orlando/
 
Description Amsterdam City Swim 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Professor Ammar Al-Chalabi took part in the 2 km Amsterdam City Swim 2015 which took place on Sunday, 06 September in Amsterdam's Central Canal and successfully raised £540.00 for the Motor Neurone Disease Association.
Year(s) Of Engagement Activity 2015
URL https://www.justgiving.com/AmmarAl-Chalabi
 
Description Ask the Experts Panel at International Symposium 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact A live audience and online audience watched a presentation and then asked questions on ALS research
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=U98WU4Zzu8s
 
Description ENCALS meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact About 50 people attended the European Network for the Cure of ALS satellite meeting at the International ALS Symposium in Dublin. There was significant discussion around clinical staging, multistep models, and genetics of ALS
Year(s) Of Engagement Activity 2016
URL http://www.encals.eu/wp-content/uploads/2016/09/20161206-program-ENCALS-satellite-Dublin.pdf
 
Description ENCALS meeting 2014 Leuven 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact ENCALS is a network of ALS centres in Europe. It was established to help develop the standards of clinical and biomedical MND research across Europe and create a more collaborative environment for researchers, industry, funding agencies and Patient Associations. However, the meeting had a very transatlantic flavour, thanks to the participation of several of the leading researchers from North America.

With around 40 speakers, as well as numerous poster presentations, there is too much to cover in a few hundred words, so I'll focus on just a few of the key themes that were covered.
Year(s) Of Engagement Activity 2014
URL http://www.encals.eu/past-meeting/encals-meeting-2014-leuven/
 
Description ENCALS meeting 2015 Dublin 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact The ENCALS meeting is an important forum for the European MND community. The aim of the meeting is to encourage younger researchers to present their data, and to meet and interact with more established members of the community.

The program highlighted state-of the-art science and clinical practice in the field of ALS. The focus was on Genes and Genomics, Cognition, C9orf72 and Novel Therapeutics, Imaging, TDP: RNA Metabolism and Disease Pathogenesis, Disease Models and Pathogenesis and Novel Biomarkers. Top international speakers provided cutting edge overviews.

The meeting in Dublin was a great success with over 30 oral presentations and 80 poster presentations and many opportunities for young researchers to enhance their network.
Year(s) Of Engagement Activity 2015
URL http://www.encals.eu/news/encals-meeting-2015-dublin/
 
Description General research dissemination videos on YouTube 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Multiple videos on YouTube, responding to interviews on ALS research
Year(s) Of Engagement Activity 2014,2015,2016
URL https://www.youtube.com/results?search_query=ammar+al-chalabi+als
 
Description JNNP Podcast 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was interviewed for a podcast about our recent finding that genetic variants that increase ALS risk, also lower the age of onset. Our paper was Editor's Choice.
Year(s) Of Engagement Activity 2019
 
Description Joint JPND Consortia Meeting, London Heathrow 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Joint JPND Consortia Meeting, 06 - 07 October 2014, London Heathrow:
In October 2014 a 1.5-day Joint JPND Consortia Meeting was organized by Project Coordinator (UK1) in London Heathrow, UK. The new format of involving four different JPND-funded project consortia (STRENGTH, SOPHIA, ALS-CarE and NEEDS in ALS) and compiling a meeting programme out of thematic sessions across four projects was a great success and all project coordinators are willing to continue this in the future. Fifty stakeholders including project coordinators, project partners, external collaborators, as well as special guests attended the sessions over two days in London.
Year(s) Of Engagement Activity 2014
 
Description Keynote presentation at International Symposium of ALS/MND Associations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Extensive discussion of the content

Invitations to speak at further conferences, two invitations to write reviews for Nature Reviews Neurology (both taken up), invitation to submit paper to Lancet Neurology and to visit the offices.
Year(s) Of Engagement Activity 2012
 
Description Lecture tour for researchers, patients and clinicians to South America 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Lectures and Question and Answer sessions were held at several locations in Uruguay and Argentina, including a university in Montevideo, 3 universities in Buenos Aires region, and a hotel in Buenos Aires city. The sessions included simultaneous translation Spanish and English and were live streamed on Facebook, as well as remaining available now. The question and answer session was with patients and carers, and lasted nearly two hours. The entire trip was coordinated by the ELA Association, a South American ALS association, which is now affiliated with the international alliance of ALS/MND Associations.
Year(s) Of Engagement Activity 2018
URL http://www.asociacionela.org.ar/index.php/pregunta-a-los-expertos-1
 
Description MND Connect 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Patient-researcher-clinician question and answer session also live-streamed
Year(s) Of Engagement Activity 2019
URL https://www.youtube.com/watch?v=KRb1HWv08gQ
 
Description MNDA Legacy Event 2019 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Tour of labs and clinics with talks by researchers and clinicians
Year(s) Of Engagement Activity 2019
 
Description MNDA Legacy Event September 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact The event was to educate the general public and those engaged with the MND Association about the research done that is funded by the MNDA, with the aim of increasing knowledge and encouraging a legacy to such research,
Year(s) Of Engagement Activity 2018
 
Description MNDA Legacy Event at King's College London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Between 40 and 70 people attended each event, consisting of research presentations, a tour of the labs, and an Ask the Experts session. The events were to raise awareness of our research, to improve donations to the patient organisation (MNDA), and to improve public understanding of our clinical and research programme. Increased donations have been reported, and feedback shows a high demand for future events.
Year(s) Of Engagement Activity 2017,2018
 
Description MNDA Legacy Video 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact During the MNDA legacy event a video was shot with the purpose of engaging with the public as much as possible.
Year(s) Of Engagement Activity 2018
URL https://youtu.be/gbESPsGZyZo
 
Description MNDA information video on our research 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A YouTube video posted also on the Motor Neurone Disease Association website, describing our research.
Year(s) Of Engagement Activity 2016
URL https://youtu.be/tKz81aFVB04
 
Description Mitsubishi Tanabe Pharma workshop on clinical staging measures in ALS 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A formal workshop on different outcome measures for clinical trials in ALS, and specifically the benefits of clinical staging systems. Clinical staging (and specifically King's Clinical Staging for ALS) was regarded as a major benefit for clinical trials and the basis of a research output (two poster presentations and a platform presentation) from the pharmaceutical company at the December International ALS Symposium in Dublin.
Year(s) Of Engagement Activity 2016
URL http://www.als.net/news/global-als-research-progress-a-report-from-2016-international-symposium-in-d...
 
Description NIHR MND Engage 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A study day on PPI
Year(s) Of Engagement Activity 2019
 
Description New Zealand Inaugural MND Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact I gave the plenary talk at the inaugural MND New Zealand research symposium which sparked multiple questions and disussions
Year(s) Of Engagement Activity 2019
URL https://anzasw.nz/events/motor-neuron-disease-mnd-new-zealand-research-conference-2019/
 
Description Scientific Advisory Board and Workshop for Platform Trials at the MGH Healey Center 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Current clinical trials are performed sequentially in ALS, which is a very slow method for a devastating fatal disease. Platform trials offer a perpetual trial design, with 3:1 active to placebo participation, and multiple simultaneous trials, greatly accelerating drug discovery and improving patient participation. This board and series of workshops aims to make such trials a reality in ALS.
Year(s) Of Engagement Activity 2018,2019
 
Description Staging presentation at Cytokinetics meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact About 220 participants attended in person, with more attending online. This was a set of three presentations on outcome measures for ALS clinical trials, with major audience participation, including voting on different measures. The number of people stating they would incorporate clinical staging as a routine part of their everyday practice increased from 5% to 25% by the end of the discussion.
Year(s) Of Engagement Activity 2016
URL http://alsmndmeasures.com/
 
Description TRICALS training 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Training in clinical staging for ALS for members of the TRICALS consortium. An analysis of responses from the training has been submitted for publication.
Year(s) Of Engagement Activity 2014,2015,2016
URL https://www.tricals.org/#1487071717028