SUMMARY MEASURE STATISTIC FOR ASSESSING THE OUTCOME OF TREATMENT TRIALS IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS

Objectives-To review the outcome measures commonly used in phase III t reatment trials of relapsing-remitting multiple sclerosis and to intro duce a method of data analysis which is clinically appropriate for the often reversible disability in this type of multiple sclerosis. Metho ds-The conventional end point measures for disability change are inade quate and potentially misleading. Those using the disability differenc e between study entry and completion do not take into account serial d ata or disease fluctuations. Rigid definitions of ''disease progressio n'' based on two measurements of change in disability several months a part, do not assess worsening after the defined ''end point'', nor the significant proportion of erroneous ''treatment failures'' which resu lt from subsequent recovery from relapses that outlast the end point. Assessing attacks merely by counting their frequency ignores the varia tion in magnitude and duration. These problems can be largely circumve nted by integrating the area under a disability-time curve (AUC), a te chnique which utilises all serial measurements at scheduled visits and during relapses to summarise the total neurological dysfunction exper ienced by an individual patient on any particular clinical scale durin g a study period. Conclusions-The ''summary measure'' statistic AUC in corporates both transient and progressive disability into an overall e stimate of the dysfunction that was experienced by a patient during a period of time. It is statistically more powerful and clinically more meaningful than conventional methods of assessing disability changes, particularly for trials which are too short to expect to disclose majo r treatment effects on irreversible disability in patients with a fluc tuating disease.