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Thus, <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> may be used as an early to intermediate end\u2010point in survival studies. The aim of the present study was to test <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> as a predictor of survival in <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an observational retrospective study of <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> patients from a tertiary referral centre over a 5\u2010year follow\u2010up period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 212 <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> patients, <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> was associated with time to death\/tracheostomy [R 0.62, 95% confidence interval (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) 0.53\u20130.70; <jats:italic>P<\/jats:italic> &lt; 0.001]. In a time\u2010to\u2010event analysis, longer <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>) 0.98, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.97\u20130.99] and multivariate Cox analyses (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 0.98, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.96\u20130.99). <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> predicted death\/tracheostomy at 4 years (<jats:italic>C<\/jats:italic>\u2010statistic 0.58; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.53\u20130.63) and at 5 years (<jats:italic>C<\/jats:italic>\u2010statistic 0.58; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.53\u20130.62).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on the present results from a large clinical cohort, <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> may be used as a new early to intermediate end\u2010point to describe the <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> natural history. <jats:styled-content style=\"fixed-case\">TTG<\/jats:styled-content> may be potentially useful as a new primary outcome measure for clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12994","type":"journal-article","created":{"date-parts":[[2016,3,26]],"date-time":"2016-03-26T12:02:12Z","timestamp":1458993732000},"page":"1117-1125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Time to generalization and prediction of survival in patients with amyotrophic lateral sclerosis: a retrospective observational 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