A placebo-controlled model to assay the onset of action of nonprescription-strength analgesic drugs.

The definition and detection of the onset of analgesic drug activity represent two of the more complicated methodologic challenges in clinical pharmacology. We addressed these issues by designing an analgesic assay with frequent posttreatment assessments to identify the first time when a subject experienced relief and when a nonprescription-strength analgesic could be distinguished from placebo. To test the feasibility of conducting this assay, 29 subjects with acute sore throat were randomized to receive 200 mg ibuprofen, 400 mg ibuprofen, or placebo under double-blind conditions. To identify the onset of analgesia, subjects used three rating scales at 5-minute intervals over the first hour. Subjects completed each series of assessments efficiently, most within 5 seconds. Each active agent was differentiated from placebo early after treatment (p < or = 0.05), and there was dose-separation. We conclude that the sore throat pain model can be used to evaluate the onset of action of nonprescription-strength analgesic agents.

Headache pain model for assessing and comparing the efficacy of over-the-counter analgesic agents.

To refine the assessment of over-the-counter analgesic agents in the treatment of muscle-contraction headache, we designed a single-dose model with attention to specific methodologic features and two relevant assessments--the percentage of subjects who achieve complete relief and the time until pain is no longer experienced. Subjects were randomly assigned to receive a single dose of 1000 mg acetaminophen, 1000 mg aspirin with 64 mg caffeine, or placebo. Under double-blind conditions, subjects rated headache pain intensity and relief over 4 hours and provided a Comparative Evaluation at the end of the trial. Both active agents were significantly distinguished from placebo on the time-point analyses (p less than 0.05) and summary end point measurements (sum of pain intensity difference [SPID], total of pain relief, percentage of patients with complete relief, percentage of treatment failures, and the Comparative Evaluation), as well as causing a faster elimination of headache (p less than 0.05). The aspirin-caffeine combination was rated higher than acetaminophen on all summary measurements, particularly SPID (p less than 0.05), with significantly more patients obtaining complete relief with aspirin-caffeine (p less than 0.01) than with acetaminophen. We conclude that this headache pain model can be used to demonstrate the efficacy of over-the-counter analgesic agents and to assess their relative efficacy.