NEFL and amyotrophic lateral sclerosis: The relationship between treatment effects (e.g., assumption for the treatment effectiveness (%) in slowing neuronal loss relative to controls) and sample size for different biomarkers and fluid sources functioning as outcome measures is summarized in Figure 6A. Sample size estimates using longitudinal follow-up data based on expected changes in serum NfL over time are shown in Figure 6B. For an interventional trial of ALS, including CSF, plasma, or serum NfL, sample sizes of 25, 35, and 16 are required, respectively, per arm with a treatment effect of 25%.