Title: Patient centred research for Degenerative Cervical Myelopathy
Funder: Department of Health and Social Care

Abstract: Degenerative Cervical Myelopathy (DCM) is a disabling condition affecting up to 2% of adults. It arises when arthritic changes compress and injure the cervical spinal cord, causing a progressive spinal cord injury. Despite treatment, less than 5% patients will make a full recovery and instead live with lifelong disabilities: a recent study found sufferers have amongst the worst quality of life of chronic diseases. Scientific advancements are therefore sorely needed. Currently the end-users, particularly patients, are poorly represented in DCM research design. This is likely contributing to the research duplication, ineffective research synthesis and a mistargeted research agenda I have found. Specifically, early insights from our engagement of patients (>1000) through Myelopathy.org, has shown frustrations focus on inadequate clinical assessments, contributing to issues with diagnosis [70% face delays, 50% initial misdiagnosis and most are never diagnosed] and accurate prognostication.Magnetic Resonance Imaging (MRI) is the hallmark of DCM diagnosis, but it is unable to specify DCM or stage and prognosticate. I have recently demonstrated its qualitative reporting is subjective and may negatively influence patient management. New quantitative, microstructural sequences have shown promise for spinal cord imaging and could offer an objective characterisation. Moreover, the value of measuring secondary, adaptive changes within the brain, is unconfirmed. This fellowship aims to build on these experiences, to incorporate patients into the direction and design of DCM research by: Establishing the top 10 research uncertainties, the core dataset for research, audit and clinical surveillance through a multi-stakeholder consensus process [RECODE-DCM] Exploring the value of advanced MR imaging techniques to improve clinical assessment [IMAGE-DCM]RECODE-DCM can be considered a series of parallel, multi-stakeholder consensus processes, including a NIHR James Lind Alliance priority-setting partnership and a minimum data set. This project is already underway, with infrastructure support from AO Spine (www.recode-dcm.com). Opinions will be gathered and refined using an eDELPHI, with final consensus recommendations made using face-to-face meetings. This fellowship period will therefore principally be used to report the findings, whilst implementing and evaluating a dissemination strategy, including the role of PodCasts and Patient Spokespersons.IMAGE-DCM will be a prospective observational study. Patients (N=30) will be recruited from the NIHR RECEDE-Myelopathy [EudraCT 2017-004856-41], a multi-centre, Phase III CTIMP of a neuro-regenerative adjuvant to surgical decompression for patients with DCM. Participants will undergo brain and spinal cord imaging, before and after treatment. Imaging sequences will include structural imaging (to assess atrophy), diffusion tensor imaging (to assess white matter and selective neuronal loss), and resting state functional MRI (to establish their functional consequences). Imaging will be compared to healthy controls (N=20) and with clinical assessments.This study will be the first to combine spinal cord and brain imaging and do so longitudinally. It will offer unique insights into their role in clinical assessment. This will have wider relevance to other spinal cord fields. This project aims to deliver international recommendations that can help researchers change outcomes sooner, whilst initiating an imaging study in response to patient concerns, to optimise the delivery of treatment and better inform sufferers.

Lay abstract: Degenerative Cervical Myelopathy (DCM) occurs when wear and tear arthritis ('degenerative') changes in the neck ('cervical') compress and injure the spinal cord ('myelopathy'). It affects up to 2% of adults, causing a progressive loss of dexterity, walking and balance, and sometimes total paralysis. As a wear and tear condition it is becoming more common with our aging population. Despite treatment less than 5% patients will make a full recovery and instead live with lifelong disabilities: a recent study found sufferers have amongst the worst quality of life of chronic diseases. Scientific advancements are therefore desperately needed.Unfortunately, we have identified that DCM research does not often answer questions that matter to DCM patients and professionals. Our early experience through Myelopathy.org, a partner charity, has shown patients are frustrated with challenges in diagnosis and clinical assessment; 70% face delays and 50% initial misdiagnosis. It is well-known most DCM sufferers are never diagnosed. However, our review of DCM research has shown that of the 4 million patients studied over the last 20 years, half were involved in studies evaluating surgical technique (not shown to change outcomes) yet imaging studies (important for diagnosis) were few and declining. Moreover, pain is a recovery priority for patients and measured in only 27% of studies. In addition, researchers are using different terminology or measurements in their investigations which makes it difficult to compare studies. These issues will slow progress. This fellowship sets out to address these problems. It aims to continue and complete an ongoing project called RECODE-DCM I started. RECODE-DCM (www.recode-dcm.com) aims to agree what questions should be answered and produce recommendations to help researchers design studies to answer them. Alongside this, I will explore the value of new imaging techniques to assess DCM (IMAGE-DCM), the early patient research priority.RECODE-DCM is already underway using early support from the AO Foundation. It combines a James Lind Alliance Priority Setting Partnership with a Core Outcomes Initiative. It will use a series of online questionnaires distributed as widely as possible, to all parties involved (patients, their supporters and professionals). These surveys are designed to gather preliminary ideas, and later work towards preliminary consensus. They will inform a final face-to-face meeting where recommendations will be produced. More information, including an explanatory animation, can be found at www.recode-dcm.com.IMAGE-DCM will apply sophisticated imaging techniques, already applied in other healthcare conditions, to thirty DCM sufferers, participating in an existing NIHR funded trial called RECEDE-DCM. By comparing these new techniques to normal assessments, before and after treatment, I aim to understand whether any of these techniques could improve assessment, and which should be further evaluated.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL