Table 1.

Biomarker Types Recognized by the FDA

Biomarker Type	Description 2	Examples relevant to ALS
Diagnostic	Disease characteristics that categorize people by the presence or absence of a specific physiological or pathophysiological state or disease	EMG for demonstrating the presence and distribution of subclinical lower motor neuron pathology
Prognostic	Baseline characteristics that categorizes patients by degree of risk for disease occurrence or progression of a specific aspect of disease (i.e. inform the natural history of the disorder in a particular patient in the absence of a therapeutic intervention)	Mutations in ALS susceptibility genes categorize individuals as being at risk for developing ALS. Some specific mutations, such as the A4V mutation in the SOD1 gene, predict an aggressive form of disease and portend a very poor prognosis for survival.
Predictive	Baseline characteristics that categorize patients by their likelihood of response to a particular treatment relative to no treatment. Such biomarkers may be used as an enrichment strategy to identify a subpopulation likely to respond to treatment intervention in a particular way	The presence of mutations in the SOD1 gene or a hexanucleotide repeat expansion in the C9ORF72 gene might be used to select for a clinical trial those patients most likely to benefit from SOD1 and C9ORF72 antisense oligonucleotides.
Pharmacodynamic	Markers that show that a biological response has occurred in a patient who has received a therapeutic intervention	Biological measurements that are abnormal (e.g. elevated) but stable over time in the absence of therapy (e.g. neurofilament light chain) as well as biomarkers of disease progression May also be drug - rather than disease- specific, indicating that a drug has, for example, engaged its intended target and exerted the intended biological effect.