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Objectives-To review the outcome measures commonly used in phase III treatment trials of relapsing-remitting multiple sclerosis and to introduce a method of data analysis which is clinically appropriate for the often reversible disability in this type of multiple sclerosis. Methods-The conventional end point measures for disability change are inadequate and potentially misleading. Those using the disability diVerence between study entry and completion do not take into account serial data or disease fluctuations. Rigid definitions of "disease progression" based on two measurements of change in disability several months apart, do not assess worsening after the defined "end point", nor the significant proportion of erroneous "treatment failures" which result from subsequent recovery from relapses that outlast the end point. Assessing attacks merely by counting their frequency ignores the variation in magnitude and duration. These problems can be largely circumvented by integrating the area under a disability-time curve (AUC), a technique which utilises all serial measurements at scheduled visits and during relapses to summarise the total neurological dysfunction experienced by an individual patient on any particular clinical scale during a study period. Conclusions-The "summary measure" statistic AUC incorporates both transient and progressive disability into an overall estimate 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 major treatment eVects on irreversible disability in patients with a fluctuating disease. (J Neurol Neurosurg Psychiatry 1998;64:726-729)

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Twenty‐four healthy male subjects participated in a study comparing plasma concentrations of nitroglycerin generated by single applications of Nitradisc 32 mg, Transiderm‐Nitro 50 mg and Nitro‐Dur 104 mg patches and from one inch of Nitrobid 2% ointment. The three patch preparations are designed to release 10 mg nitroglycerin systemically over a 24 h period. Nitrobid ointment is intended to deliver 15 mg nitroglycerin per inch of ointment, and to be reapplied at least every 8 h. Blood was taken for nitroglycerin assay up to and including 24 h after each application. Assay for nitroglycerin was performed using a gas chromatography‐mass spectrometry technique. Plasma concentrations of nitroglycerin were sustained up to the 24 h mark with all three patch preparations, but not with application of Nitrobid ointment. Nitrobid was associated with a rapid rise in nitroglycerin plasma concentrations maximal 1 h after application. Plasma concentrations of nitroglycerin absorbed from Nitrobid ointment fell below those absorbed from all three patch preparations after 8 h. Clinically, all four formulations were similar with respect to side effects, with headache and dizziness being the most common.