Table 2.

Primary, secondary and exploratory outcome measures in phase III trials for MS

Primary outcome measures
Clinical	Expanded Disability Status Scale (EDSS): 3 or 6 months confirmed disability worsening or improvement
	Relapses: annualized relapse rate, time to second relapse (conversion to clinically definite MS)

Secondary outcome measures
Clinical	MS Functional Composite (MSFC): timed 25-foot walk test, nine-hole peg test, paced auditory serial addition task or symbol digit modalities test
Paraclinical	T2-hyperintense lesions
	Gadolinium-enhancing T1 lesions
	Whole brain atrophy

Exploratory outcome measures
Clinical	As candidate component of MSFC: low-contrast letter acuity test
	Patient-reported outcome measures: e.g. quality of life, depression and anxiety, fatigue, specific functional domains
Paraclinical—imaging	Volumetric measures of specific structures (e.g. thalamus, upper cervical cord area)
	Persisting black holes
	Functional MRI for analysis of functional connectivity
	Diffusion tensor imaging to examine brain tissue integrity
	Magnetization transfer ratio MRI as a marker for brain myelin content
	Optical coherence tomography
Paraclinical—biomarkers	Biomarkers in body fluids: in CSF or blood
Composite	No evidence of disease activity (NEDA): typically covering (confirmed) EDSS progression, relapse rate and formation of MRI lesions; whole brain volume increasingly included (i.e. ‘NEDA-4’)
Electronic devices	Assess MS system, Glove analyzer, accelerometers, etc.

CSF cerebrospinal fluid, MRI magnetic resonance imaging, MS multiple sclerosis