Development of a Prognostic Model of Respiratory Insufficiency or Death in Amyotrophic Lateral Sclerosis.

A clinically useful model to prognose onset of respiratory insufficiency in amyotrophic lateral sclerosis (ALS) would inform disease interventions, communication, and clinical trial design. We aimed to derive and validate a clinical prognostic model for respiratory insufficiency within six months of presentation to an outpatient ALS clinic.We used multivariable logistic regression and internal cross-validation to derive a clinical prognostic model using a single-center cohort of 765 ALS patients who presented between 2006 and 2015. External validation was performed using the multicenter Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database with 7083 ALS patients. Predictors included baseline characteristics at first outpatient visit. The primary outcome was respiratory insufficiency within six months, defined by initiation of non-invasive ventilation, forced vital capacity <50% predicted, tracheostomy, or death.Of 765 patients in our center, 300 (39%) had respiratory insufficiency or death within six months. Six baseline characteristics (diagnosis age; delay between symptom onset and diagnosis; forced vital capacity; symptom onset site; ALS Functional Rating Scale-Revised (ALSFRS-R) total score; and ALSFRS-R dyspnea score) were used to prognose the risk of the primary outcome. The derivation cohort c-statistic was 0.86 (95% confidence interval (CI), 0.84-0.89). Internal cross validation produced a c-statistic of 0.86 (95% CI, 0.85-0.87). External validation of the model using the PROACT cohort produced a c-statistic of 0.74 (95% CI, 0.72-0.75).We derived and externally validated a clinical prognostic rule for respiratory insufficiency in ALS. Future studies should investigate interventions on equivalent high-risk patients.