Pain responder analysis: use of area under the curve to enhance interpretation of clinical trial results.
Interpretation of results on patient-reported pain outcomes from clinical trials should be meaningful to patients and healthcare providers. This study applied an area-under-the-curve (AUC) analysis to responder profiles in a clinical trial of pregabalin for the treatment of fibromyalgia (FM). Data were from a 14-week, randomized, placebo-controlled trial of pregabalin (300, 450, or 600 mg/day) for the treatment of FM in patients meeting American College of Rheumatology criteria for FM and with a baseline pain score of at least 40 mm on the 100-mm pain visual analogue scale. Pain was evaluated in a daily diary by patients using an 11-point numeric rating scale (0 = no pain, 10 = worst possible pain). Response profiles on pain improvement scores and their differences between pregabalin and placebo were assessed using the AUC (derived using the trapezoidal rule) from the responder curve (vertical axis, proportion of subjects; horizontal axis, minimum percent improvement in pain). The AUC can be interpreted as if all responders were improved by the same percentage equal to the AUC divided by 100. The AUCs (2,100 for placebo, and 2,944, 3,170, and 3,349 for pregabalin 300, 450, and 600 mg, respectively) can be considered as if every responder improved by 21, 29, 31, and 33.5% in the responder's respective treatment group. Pain improvement was significantly better with pregabalin (P < 0.05), with pregabalin responders improving by 8.4% (300 mg/day), 10.7% (450 mg/day), and 12.5% (600 mg/day) more than placebo responders. This novel approach demonstrates that responder profiles can provide an enhanced interpretation of pain outcomes for patient care and symptom management.