Neurological diseases cause a massive burden, which will increase as populations age. Rapid advances in our understanding of disease mechanisms must be translated into human benefits. We cannot stop once technologies have been developed, but must ensure that evidence and pipelines are in place for their implementation to reduce burden and inequalities.
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The global burden associated with neurological diseases is increasingly being recognized. On the basis of data from 2017, the estimated total number of disability-adjusted life years associated with neurological diseases in the WHO European region was 41.1 million, and the total number of deaths was 1.97 million. These numbers equate to 13.3% of total disability-adjusted life years and 19.5% of total deaths in this region, and these statistics are likely to get worse as the population ages1. In response to these and other findings, many campaigns have been initiated to increase investment into research, improved services, training and education. The European Academy of Neurology (EAN) — the ‘home of neurology’ — is integral to these initiatives.
Few would argue against investment in science that will lead to major breakthroughs in our understanding of the pathophysiology of disease and the development of new treatments, biomarkers and other technologies. However, translation of new discoveries into benefits for patients, populations and wider society is also vital. The temptation has been to focus on bridging the first translation gap by turning discoveries into interventions and technologies, while neglecting the second translation gap that must be addressed to implement those interventions and technologies in everyday clinical practice2.
Consider the development of relatively simple interventions, such as anti-seizure medications or treatments for Parkinson disease. The first translation gap is typically bridged via a pathway that terminates with the licensing of treatments on the basis of short-term randomized, placebo-controlled trials3,4. But the evidence derived from these trials does little to inform everyday decision making for long-term conditions, when a choice among alternatives must be made. Less attention is paid to the generation of evidence to close the second translation gap in order to ensure that services are accessible and minimize, rather than exacerbate, health inequalities and associated burdens5,6. Similarly, for more complex interventions, such as thrombectomy for stroke, we need good evidence to inform the co-ordination of a complex emergency system that ensures access to appropriate treatment and aftercare.
This second translation gap is the overarching theme of the 2022 EAN Annual Congress, the programme for which includes plenary sessions and focused workshops that address a range of challenges and solutions. The aim of this theme is to highlight the fact that we have a major opportunity to reduce the burden of neurological diseases by ensuring that currently proven technologies are implemented and widely accessible. Similarly, the theme highlights the fact that we must ensure that new treatments and technologies are developed using paradigms and methodologies that enable unimpeded implementation into clinical practice. Failure to do so will inevitably result in the maintenance, and probable worsening, of health inequalities among people with neurological conditions, and will leave unaddressed uncertainties about whether treatments and services represent good value for money and the extent of health gains and savings that can be made. The range of challenges that need to be overcome is broad.
“we have a major opportunity to reduce the burden of neurological diseases”
One major challenge is to ensure that randomized controlled trials — which remain the primary method for assessing the efficacy of treatments — generate clinically useful information. When undertaking clinical trials in neurological conditions, it is important to consider whether we are measuring the right outcomes at the right time points, and whether international consensus exists with respect to what those outcomes should be. The use of appropriate outcome measures is particularly important in trials that assess the clinical and cost effectiveness of interventions. The COMET initiative7 provides a methodology and framework to develop core outcome sets, and several core outcomes sets for neurological conditions have been developed or are in development. This process involves bringing clinicians and patients together and using consensus methods to determine what the core outcome measures should be. This approach should ensure that trials address patients’ needs and should reduce the research waste and inefficacy that can result from the use of different outcomes in different trials, which makes it difficult to get an overview of existing evidence.
A particular challenge is posed by the development and testing of treatments for rare diseases — which, in combination, account for a substantial proportion of patients seen in neurology clinics — because the sample sizes required for clinical trials can be difficult to achieve. Nonetheless, treatment options are emerging as a result of important advances in our understanding of the mechanisms that underlie these diseases, so international collaboration and the development of effective international networks is vital to overcome the difficulties caused by small populations8 and to close the translation gap. Even some apparently common neurological diagnoses, such as epilepsy, are really umbrella diagnoses that include many rare diagnoses9, and similar challenges must be overcome to develop specific treatments that truly influence the underlying biology of these rare conditions.
Another considerable challenge is the assessment of interventions other than therapeutics, such as diagnostic technologies and biomarkers. Paradigms for testing these are less established10, particularly where technologies are evolving or rapidly advancing. For example, MRI is widely available, but new MRI sequences are continually evolving and seeping into clinical practice, and adequate evaluation of their effectiveness is rarely undertaken. Similarly, the use of genomics and other ‘omics’ technologies is generating biomarkers for susceptibility, severity, treatment responses and more in many neurological diseases, but evaluation of these biomarkers can come at a substantial cost to health services, hindering their translation into clinical use.
Finally, the development and implementation of clinical guidelines is an important element of translating evidence into practice. The EAN, along with other stakeholders, has an established programme of guideline development, and such guidelines inform policy and practice. When done well, the generation of these guidelines can be a labour-intensive endeavour, including critical appraisal and assimilation of available evidence, that ultimately produces graded, evidence-based guidance. However, the production of guidelines is only one step in the pipeline — action also needs to be taken to ensure that guidance is implemented and adopted by healthcare systems. This step is also challenging, particularly when guidance comes from organizations that are external to the local health systems that are being asked to implement them.
“Bridging the second translation gap is vital if people […] are to benefit from important advances in our understanding of disease”
Bridging the second translation gap is vital if people with neurological conditions are to benefit from important advances in our understanding of disease and therapeutic development. The challenges and opportunities discussed above are just a few examples, but they give a flavour of the complexities. There are countless more, many of which are addressed by the programme at the 2022 EAN Congress, where the focus is on ‘getting evidence into practice’.
Deuschl, G. et al. The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017. Lancet Public Health 5, e551–e567 (2020).
Cooksey, D. A Review of UK Health Research Funding https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/228984/0118404881.pdf (HM Treasury, 2006).
Stowe, R. L. et al. Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database Syst. Rev. 2, CD006564 (2008).
Lattanzi, S. et al. Adjunctive cenobamate for focal-onset seizures in adults: a systematic review and meta-analysis. CNS Drugs 34, 1105–1120 (2020).
Taylor, C. et al. Care in Europe after presenting to the emergency department with a seizure; position paper and insights from the European Audit of Seizure Management in Hospitals. Eur. J. Neurol. 29, 1873–1884 (2020).
Hillmann, S. et al. Temporal changes in the quality of acute stroke care in five national audits across Europe. BioMed Res. Int. 2015, 432497 (2015).
Kirkham, J. J. et al. Core Outcome Set-STAndards for Development: The COS-STAD recommendations. PLoS Med. 14, e1002447 (2017).
Reinhard, C. et al. The European reference network for rare neurological diseases. Front. Neurol. 11, 616569 (2021).
Epi25 Collaborative. Sub-genic intolerance, ClinVar, and the epilepsies: a whole-exome sequencing study of 29,165 individuals. Am. J. Hum. Genet. 108, 2024 (2021).
National Institute for Health and Clinical Excellence. Diagnostics Assessment Programme Manual https://www.nice.org.uk/media/default/about/what-we-do/nice-guidance/nice-diagnostics-guidance/diagnostics-assessment-programme-manual.pdf (NICE, 2011).
A.G.M. is a National Institute for Health Research (NIHR) Senior Investigator and also part funded by NIHR ARC North West Coast. The views expressed in this article are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care.
The author declares no competing interests.
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Marson, A.G. The importance of getting evidence into practice.
Nat Rev Neurol (2022). https://doi.org/10.1038/s41582-022-00689-8