{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:52:20Z","timestamp":1776847940681,"version":"3.51.2"},"reference-count":48,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"unspecified","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014076","name":"Stichting ALS Nederland","doi-asserted-by":"publisher","award":["Project EVIDENCE"],"award-info":[{"award-number":["Project EVIDENCE"]}],"id":[{"id":"10.13039\/501100014076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,9,20]]},"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disease with no effective treatment to date. Despite numerous clinical trials, the majority of studies have been futile in their effort to significantly alter the course of the disease. However, these studies may still provide valuable information for identifying patient subgroups and generating new hypotheses for future research. Additionally, synthesising evidence from these studies may help overcome the limitations of individual studies. Network meta-analysis may refine the assessment of efficacy in specific patient subgroups, evaluate intervention characteristics such as mode of administration or biological mechanisms of action, and rank order promising therapeutic areas of interest. Therefore, we aim to synthesise the available evidence from ALS clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will conduct a systematic review to identify all clinical trials that assessed disease-modifying pharmaceutical therapies, cell therapies, or supplements in patients with ALS. Outcomes of interest are clinical disease progression outcomes and survival. We will conduct this search in the period Q4 2024 in three databases: PubMed, Embase and ClinicalTrials.gov for studies from 1999 to 2023. Individual patient data and aggregate data will be collected and subsequentially synthesised in meta-analytical models. The final model will be presented as an open-source web application with biannual updates of the underlying data, thereby providing a \u2018living\u2019 overview of the ALS clinical trial landscape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>No ethics approvals are required. Findings will be presented at relevant conferences and submitted to peer-reviewed journals. Data will be stored anonymously in secure repositories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-087970","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T06:00:58Z","timestamp":1730440858000},"page":"e087970","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Living systematic review and comprehensive network meta-analysis of ALS clinical trials: study protocol"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4871-2567","authenticated-orcid":false,"given":"Floris T","family":"Van Loon","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-1892","authenticated-orcid":false,"given":"Georgios","family":"Seitidis","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Ioannina, Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-4592","authenticated-orcid":false,"given":"Dimitris","family":"Mavridis","sequence":"additional","affiliation":[{"name":"Department of Primary Education, University of Ioannina, Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi W J","family":"van Unnik","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daphne N","family":"Weemering","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard H","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilianna","family":"Bethani","sequence":"additional","affiliation":[{"name":"School of Medicine, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Nikolakopoulos","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Ioannina, Ioannina, Greece"},{"name":"Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-5967","authenticated-orcid":false,"given":"Ruben P A","family":"van Eijk","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands"},{"name":"Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"2025121602354296000_14.10.e087970.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.153"},{"key":"2025121602354296000_14.10.e087970.2","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-4-3","article-title":"Amyotrophic lateral sclerosis","volume":"4","author":"Wijesekera","year":"2009","journal-title":"Orphanet J Rare 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