Table 6 Validation of magnetic resonance imaging lesion volumes as a surrogate outcome: explanations of possible discordance between clinical and surrogate lesion volume measures

If clinical endpoint shows a benefit but lesion volume does not:

   Imaging methods are insensitive to neuroprotection

   Clinical benefit not mediated by neuroprotection

If lesion volume shows a benefit but the clinical endpoint does not:

   Trial design or clinical measures are insensitive to detecting a

clinical effect

   Toxicity offsets neuroprotective effect