Table 5.
Estimated total sample size savings in a random slopes model of ALSFRS-R progression that includes the prognostic marker and covariate(s)
| Prognostic Marker | Unadjusted | Covariate(s) included | |||
|---|---|---|---|---|---|
| Core clinical predictors 1 | ENCALS Predictor score 2 | Core clinical predictors 1 + NfL | ENCALS predictor score 2 + NfL | ||
| ENCALS linear score | −9.0% | −10.4% | -- | −33.6% | -- |
| Serum NfL | −30.9% | −33.4% | −33.6% | -- | -- |
| Serum pNfH | −4.0% | −13.3% | −12.3% | −33.2% | −33.5% |
| Urinary p75 ECD | −7.6% | −13.2% | −16.4% | −37.2% | −37.5% |
| Serum uric acid | −0.8% | −8.2% | −8.2% | −33.2% | −33.3% |
| Serum creatinine | 1.2% | −8.3% | −7.8% | −33.0% | −33.2% |
| Serum albumin | 1.9% | −8.1% | −7.4% | −33.2% | −33.4% |
| Serum CRP | −0.3% | −10.3% | −9.3% | −33.5% | −33.4% |
| Plasma miR-181ab | −2.0% | −9.7% | −10.6% | −34.2% | −35.4% |
| NfL+miR181ab poor Px 3 | −20.7% | −9.9% | −24.8% | −34.5% | −34.1% |
| NfL+miR181ab poor Px 4 | −25.1% | −9.3% | −28.9% | −33.8% | −34.9% |
| NfL median split 5 | −26.5% | −29.2% | −29.4% | −34.2% | −34.4% |
| NfL 4-level split 6 | −31.4% | −33.8% | −33.4% | −34.8% | −34.6% |
Values indicate the combined percent sample size reduction when the prognostic identified by a row heading is added to covariates described in column headings, in a hypothetical clinical trial with ALSFRS-R as the outcome measure, assuming the experimental therapeutic has a 30% treatment effect.
Core clinical predictors of functional decline include bulbar onset, diagnostic delay, and ΔFRS.
ENCALS predictor score is derived from ΔFRS, bulbar onset, diagnostic delay, age at onset, SVC percent predicted, El Escorial definite ALS, presence of FTD, and presence of a C9orf72 repeat expansion.
Poor prognosis based on published optimal combination of NfL and miR-181ab, in which a poor prognostic factor is defined as either (NfL > 109.8 pg/mL) or (NfL > 59.0 pg/mL and miR-181ab > 39,300 UMI) 11.
Poor prognosis based on recalculated combination of NfL and mIR-181ab, using thresholds obtained from the current dataset; a poor prognostic factor is defined as either (NfL > 80.8 pg/mL) or (NfL > 44.8 pg/mL and mIR-181ab > 24,590 UMI2).
Median serum NfL = 67.9 pg/mL
Serum NfL 4-level split is at the 33rd, 50th, and 67th percentiles (44.8 pg/mL, 67.9 pg/mL, and 80.8 pg/mL, respectively) , i.e., tertiles and median, rather than quartiles to mimic construction of the NfL+miR18ab measure 11.