Linear estimates of disease progression predict survival in patients with amyotrophic lateral sclerosis

We have shown that linear estimates of rates of disease progression (LEP), derived from isometric myometry [grip or foot dorsiflexion (FD) strength] a nd forced vital capacity (FVC%), are clinically and statistically significa nt predictors of survival of patients with amyotrophic lateral sclerosis (A LS) from date of disease onset and, except those based on grip strength, of survival from the date of measurement. We tested these results in 2 additi onal groups of patients: 1) those who participated in a previously reported Protropin (GH) study; and 2) those enrolled in two other clinical trials ( group 2), The LEP were derived and tested as predictors of survival. In a C ox proportional hazards model, LEP based on all measures predicted survival from disease onset in both groups of patients. Using cutoff points determi ned within the original group to stratify patients in the validation groups into faster and slower progressing subgroups resulted in statistically sig nificant separation of survival curves from disease onset in group 2 for al l LEP and in group 1 (the GH group) for LEP derived from FD strength; and, for survival from date of measurement in group 2, when stratified by LEP ba sed on FD strength or FVC%, LEP based on data generated by myometry or pulm onary function studies have now been shown to predict survival in 3 unrelat ed groups of patients with ALS entering clinical trials. Their precise use in clinical trial design needs to be explored further. (C) 2000 John Wiley & Sons, Inc.