Assessing treatment outcomes in multiple sclerosis trials and in the clinical setting

Key Points Many clinical response measures are used in clinical trials: relapse-derived measures reflect the clinical effect of inflammatory activity, whereas disability-derived measures reflect the effect of neurodegeneration Among the neuroimaging measures used in clinical trials, lesion-derived metrics capture inflammatory activity, whereas brain atrophy measures reflect neurodegeneration; the choice of measure should reflect the drug's mechanism of action Owing to technical, financial and logistical barriers, most of the clinical and neuroimaging response measures used in trials are not used in the clinical setting All clinical and neuroimaging response measures used in the clinic should have a clear meaning at the individual level Combined (clinical and MRI) outcomes can be used in both trial and clinic settings, although their increased sensitivity to detect treatment effects particularly favours their use in trials The use of patient-reported outcome measures is important because they capture the impact (and effects) of the intervention on clinical disability, MRI parameters, daily activities and quality of life In clinical trials, outcome measures might determine whether a drug is worthy of further development; in the clinic, they might guide important treatment decisions. Here, Tur and colleagues help clinicians and researchers navigate the maze of options for clinical, neuroimaging, patient-reported and composite outcome measures in multiple sclerosis. Increasing numbers of drugs are being developed for the treatment of multiple sclerosis (MS). Measurement of relevant outcomes is key for assessing the efficacy of new drugs in clinical trials and for monitoring responses to disease-modifying drugs in individual patients. Most outcomes used in trial and clinical settings reflect either clinical or neuroimaging aspects of MS (such as relapse and accrual of disability or the presence of visible inflammation and brain tissue loss, respectively). However, most measures employed in clinical trials to assess treatment effects are not used in routine practice. In clinical trials, the appropriate choice of outcome measures is crucial because the results determine whether a drug is considered effective and therefore worthy of further development; in the clinic, outcome measures can guide treatment decisions, such as choosing a first-line disease-modifying drug or escalating to second-line treatment. This Review discusses clinical, neuroimaging and composite