Trajectories of Outcome in Neurological Conditions (TONiC)

 TONiC is a national study examining the factors that influence quality of life in people with neurological conditions. It is the largest study of its kind ever performed in the world. So far, about 1 in 4 people with MND living in the UK have joined TONiC. The more people join and contribute their experiences and view points, the more powerful the results.

The results from TONiC will be used to improve services by identifying aspects of MND that are important to people living with MND, but which might be underestimated by current service provision. As part of TONiC we will develop ‘outcome measures’ that can be used for future studies.
People with MND at any stage of their illness are welcome to participate, the “tick box” questionnaires are easily done at home at your own pace. If you cannot write, someone can tick your chosen response on your behalf. If you would like to take part you can contact the local TONiC champion at a centre near you – visit https://tonic.thewaltoncentre.nhs.uk, or you can contact the study team direct (0151 529 5668/2980) or e-mail tonic@thewaltoncentre.nhs.uk

Study titleTrajectories of Outcome in Neurological Conditions (TONiC)
UK Chief InvestigatorProfessor Carolyn Young
Research summaryQuality of Life (QoL) for people with disabling neurological conditions is affected by a range of factors, which have received considerable previous research attention. However, clinicians’ knowledge could be enhanced by two areas of additional enquiry.
1) Wide consultation:
a) Interviewing a range of people with the conditions (First stroke, traumatic brain injury, multiple sclerosis, neuromyelitis optica, spinal conditions, motor neurone disease), about factors influencing QoL;
b) Multi-disciplinary Panel- patients and clinicians- experienced in the conditions;
c) Draft Questionnaire assessed for relevance by people with the conditions.
Our earlier work suggested the importance of QoL factors like fatigue. We will utilise suitable previously-validated condition-specific QoL measures. It is possible that unvalidated or little-tested QoL factors will be suggested. If so, we will develop a new measure and test using
d) Focus Groups- patients’ and clinicians’ opinions on QoL factors, and priority factors for analysis.
Such analysis would have greater validity than that used previously as it would reflect a wide range of patient and clinician opinion.

2) Testing factors for QoL-influence:
e) Self-report Questionnaire data from a large Cross-Section of people with the conditions;
f) To assess QoL over time, questionnaire participants offered the choice to volunteer to complete the Questionnaire 6 months, 12 months, and 2 years later.
Data would be analysed using statistical techniques to determine the nature and strength of relations between different factors.
The researchers will develop and test models of factors affecting QoL and compare whether models vary between conditions.
The model structure reflects World Health Organisation impairment, activity, and participation areas. The benefit of this approach is that we are testing factors which reflect concerns of people experienced in the conditions, to develop a model which may assist interventions to improve Quality of Life.
Inclusion/exclusion criteriaInclusion criteria:
1. Diagnosed with one of the following diseases (first stroke, traumatic brain injury (TBI), multiple sclerosis (MS),neuromyelitis optica (NMO), spinal conditions or motor neurone disease (MND)). 2. Adults who are capable of answering questionnaires. 3. Capable of informed consent. 4. Have given informed consent. 5. For interviews, adults with the condition who are able to speak to a researcher, for any people with communication difficulties we will interview people with the assistance of a speech therapist or other support if necessary. For the questionnaire phase, we will not exclude people with difficulty writing due to their neurological condition and allow use of a scribe who records the answer chosen by the participant. 5. Participants wanting to do the qualitative work and cross sectional questionnaire stage can be at any time after diagnosis and participants wanting to do the longitudinal questionnaires commence within one year of diagnosis.

Exclusion criteria:
1. Not capable of informed consent 2. Have not given informed consent 3. Suffering from a concomitant serious medical or psychiatric condition
Current statusActive – recruiting
LocationsSites recruiting MND patients:

England:
Barnstaple
Basildon
Brighton
Bury St. Edmunds
Cambridge
Cumbria Partnership Community Care (Site details TBC)
Dartford
Kings Lynn
Leicester
United Lincolnshire Hospitals NHS Trust (Site details TBC)
Liverpool
London (King's College Hospital)
London (North East London NHS Foundation Trust) (Site details TBC)
London (Northwick Park Hospital)
London (Royal Free Hospital)
Maidstone and Tunbridge Wells NHS Trust (Site details TBC)
Newcastle
Norwich
Oxford
Peterborough
Plymouth
Portsmouth
Preston
Salford
Sheffield
Southampton
Stoke (Haywood Hospital)
Stoke (Royal Stoke University Hospital)
Wonford, Devon
Worcester
York

Scotland:
Edinburgh

Wales:
Cardiff
Cwm Taf Morgannwg University Health Board (Site details TBC)
Llanelli
Swansea
Contact detailsCoordinating centre:
Telephone: 0151 529 5668 / 0151 529 2980 or email: tonic@thewaltoncentre.nhs.uk
Recruitment group(s)Patients with neurological conditions.
Recruitment target(s)16,500 patients nationally (This includes patients with MND and also patients with other neurological conditions).
Key datesRecruitment start date (actual): 01 June 2012
Recruitment end date (target): 30 November 2020.
Funder(s)Motor Neurone Disease Association
SponsorWalton Centre for Neurology & Neurosurgery NHS Foundation Trust
Study designLongitudinal, Observational (questionnaire).
Intervention (if applicable)Not applicable.
Phase (if applicable)Not applicable.
Outcome measures- To develop a biopsychosocial model of factors affecting quality of life (QoL) in different neurological conditions: multiple sclerosis (MS), motor neurone disease (MND), neuromuscular (NM) disorders, traumatic brain injury (TBI), spinal conditions, first stroke and neuromyelitis optica (NMO).
- To examine the validity of the model over time.
- To develop scales that measure different aspects of QoL in neurological illnesses, where generic scales are not available.
- To test the validity of some existing generic measures.
Publications / Results reportsPublished papers:
Risk factors for social withdrawal in amyotrophiclateral sclerosis/motor neurone disease, 2018
Mapping ALSFRS-R and ALSUI to EQ-5D in Patients with Motor Neuron Disease, 2018
Development and validation of Spasticity Index—Amyotrophic Lateral Sclerosis, 2018
Economic Studies in Motor Neurone Disease: A Systematic Methodological Review, 2017

Platform presentations:
- Professionals’ opinions on the physical factors affecting quality of life in multiple sclerosis and motor neurone disease: pilot work from the Trajectories of Outcomes in Neurological Conditions study. O'Sullivan B, Rose N, Griffiths J, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions (TONiC) Study Group (2013). Abstract in Journal of Neurology 2013;260, S1: 26. Presented at 23rd Meeting of the European Neurological Society, Barcelona, Spain. June 2013.
- Perceptions of quality of life in motor neurone disease: views of patients and patient family support group. Qualitative results from the Trajectories of Outcome in Neurological Conditions study. Ando H, Cousins R, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions (TONiC) Study Group (2013). Abstract in Journal of Neurology 2013;260 (S1): 23-24.Presented at 23rd Meeting of the European Neurological Society, Barcelona, Spain. June 2013.
- Understanding Quality of Life in Motor Neurone Disease: Qualitative Explanations from the Trajectories of Outcome in Neurological Conditions Study (TONiC). Ando H, Cousins R, Young CA. Abstract in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2013;14(sup2):7. DOI: 10.3109/21678421.2013.838413/011.Presented at 24th International Symposium on ALS/MND, Milan, Italy.
- The role of hope in MS and MND. Young CA (2016). Presented at Palliative Care in Neurology, London. 2016.
- Physical and Psychological influences upon Quality of Life in Motor Neurone Disease/ALS. Young CA, Mills RJ, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group (2016). Abstract in Amyotrophic Sclerosis & Frontotemporal Degeneration 2016;17 (S1):26.Presented at 27th International Symposium on MND/ALS Dublin. 7-9 December 2016.
- Development and validation of Spasticity Index – Amyotrophic Lateral Sclerosis (SI-ALS). Young CA for TONiC Study Group (2017).Presented at ABN, Liverpool, UK. 3-5 May 2017.
- Understanding quality of life in ALS/MND by modelling patient-reported outcomes. Young CA for TONiC Study Group.Presented at 29th International Symposium on ALS/MND, Glasgow, Scotland, UK. 7-9 December 2018.

Posters:
- Perceptions of quality of life in motor neurone disease: views of patients and patient family support group. Qualitative results from the Trajectories of Outcome in Neurological Conditions study. Ando H, Cousins R, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions (TONiC) Study Group Presented at 23rd Meeting of the European Neurological Society, Barcelona, Spain from 8 – 11th June 2013. Abstract in Journal of Neurology 2013;260, S1: 23-24
- Bulbar symptoms as physical determinants of quality of life in patients with Amyotrophic Lateral Sclerosis: A systematic review. Mohammad MH, Young CA on behalf of the TONiC Study Group Presented at 24th International Symposium on MND Milan from 6-8 December 2013
- Psychosocial factors affecting quality of life in motor neurone disease: A systematic review of the literature. Nee LD, Goldstein LH, Young CA (2013). Presented at 24th International Symposium on MND Milan from 6-8 December 2013
- Functioning, fatigue and psychosocial features of ALS/MND: associations, change over time and impact on patient quality of life. Gibbons CJ, Young CA on behalf of the TONiC Study Group Presented at 24th International Symposium on MND Milan from 6-8 December 2013
- What is unique about quality of life in Motor Neurone Disease? A qualitative query. Young CA, Ando H, Cousins R on behalf of the TONiC Study Group Presented at 25th International Symposium on MND Brussels from 5-7 December 2014
- ALS symptoms, disability and quality of life: Literature review and model generation. Aynsley G, Goldstein L, Young CA (2014). Presented at 25th International Symposium on MND Brussels from 5-7 December 2014
- The patient experience of spasticity in motor neurone disease. Milinis K, Young CA, on behalf of the TONiC study group Presented at 25th International Symposium on MND Brussels from 5-7 December 2014
- The structure and use of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. Young CA, Tennant A on behalf of the TONiC study group Presented at 26th International Symposium on MND Orlando from 11 – 13 December 2015
- The Fatigue to Quality of Life relationship in MND: Is gender moderating the effect? Young CA, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 26th International Symposium on MND Orlando from 11 – 13 December 2015
"- Coping strategies used by people with MND. Holland D, Mills RJ, Tennant A, Young CA on behalf of the Trajectories of Outcomes in Neurological Conditions Study Group
Presented at 26th International Symposium on MND Orlando from 11 – 13 December 2015 "
- Psychological Distress in Motor Neurone Disease and its correlation with use of Alcohol or Drugs and other negative Coping Strategies. Holland D, Mills RJ, Tennant A, Young CA on behalf of the TONiC group (2015). Presented at 26th International Symposium on MND Orlando from 11 – 13 December 2015
- Coping Strategies, Gender and Disease Subtype in MND/ALS. Young CA, Mills RJ, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Influences on Quality of Life for people with MND/ALS: Progress of the Trajectories Of Outcome in Neurological Conditions Study. Young CA, Dyas-Wolff L, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Co-morbidities In People With Motor Neurone Disease/ALS. Sangheli A, Mills RJ, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Onset type and consequent health status in MND/ALS. Young CA, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Stigma in people with Motor Neurone Disease/ALS. Young CA, Mc-Sloy Poli C, Tennant A on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Depression and anxiety in People with Motor Neurone Disease/ALS. James E, Mills RJ, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- The WHO disability assessment Scale in the measurement of activity and participation in Motor Neurone Disease/ALS. James E, Tennant A, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Economic evaluations, cost studies and utility studies in Motor Neurone Disease/ALS: a systematic methodological review. Moore A, Hughes D, Young CA on behalf of the TONiC study group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- The relationships between fatigue, sleep and disability in Motor Neurone Disease. Mills RJ, Tennant A, Young CA on behalf of the Trajectories of Outcome in Neurological Conditions Study Group Presented at 27th International Symposium on MND/ALS Dublin from 7-9 December 2016
- Risk factors for social withdrawal in Motor Neurone Disease/Amyotrophic Lateral Sclerosis. Schlüter DK, Tennant A, Young CA on behalf of the TONiC group Presented at 28th International Symposium on MND/ALS Boston from 8-10 December 2017
- Use of coping strategies in Motor Neurone Disease/Amyotrophic Lateral Sclerosis: association with demographic and disease-related characteristics. Schlüter DK, Mills R, Young CA on behalf of the TONiC group Presented at 28th International Symposium on MND/ALS Boston from 8-10 December 2017
- Physical and mental factors affecting perceived stigma amongst people with Motor Neuron Disease/ALS. Edge R, Young CA on behalf of the TONiC group Presented at 28th International Symposium on MND/ALS Boston from 8-10 December 2017
- Associations between pain, mood and quality of life in Motor Neurone Disease/Amyotrophic Lateral Sclerosis. Edge R, Au Yeung J, Young CA on behalf of the TONiC group Presented at 28th International Symposium on MND/ALS Boston from 8-10 December 2017
- Mapping to the EQ-5D-5L from clinical data in people with Motor Neurone Disease/Amyotrophic Lateral Sclerosis. Moore A, Young CA, Hughes D on behalf of the TONiC group Presented at 28th International Symposium on MND/ALS Boston from 8-10 December 2017
- Risk factors for depression in motor neurone disease. Schlüter DK, Miele G, Mills R, Young CA on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Neuropathic pain in ALS/MND. Syrimi ZJ, Mills RJ, Young CA on behalf of TONiC study group . Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Investigating depression and disability in a cross-sectional sample of people with ALS/MND. Granger N, Schlüter DK, Bredin A, Mills RJ, Young CA on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Social factors and their contribution to quality of life in ALS/MND: a systematic review of the literature. Nee L, Granger N, Young CA. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Smoking is associated with younger age of onset in motor neurone disease. Mills RJ, Tennant A, Young CA on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Can you validly use a total ALSFRS-R score? A Rasch analysis to provide interval scale estimates. Young CA, Paris-Davies J, Mills RJ, Tennant A on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Coping in motor neurone disease/amyotrophic lateral sclerosis: qualitative analysis of themes. Young CA, Ando H, Cousins R on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Equity of access to Riluzole for individuals with MND/ALS in the UK. Schlüter DK, James BE, Mills R, Young CA on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- Hope in motor neurone disease/amyotrophic lateral sclerosis: qualitative analysis of concepts and domains. Young CA, Ando H, Cousins R on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
- World Health Organisation Disability Assessment Schedule (WHODAS-2.0) in MND/ALS. James ECA, Mills RJ, Tennant A, Young CA on behalf of TONiC study group. Presented at 29th International Symposium on ALS/MND, Glasgow from 7-9 December 2018.
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