Twin crossover relative potency analgesic assays in man. I. Morphine vs. morphine

Although the four-point relative potency assay using crossover design has proven a powerful technique for the clinical evaluation of analgesics in patients with chronic pain, excessive dropouts have made this design impractical in postoperative pain. In a relative potency assay comparing single graded intramuscular doses of morphine standard and morphine test in postoperative patients, we have managed to circumvent this difficulty while preserving many of the advantages of a complete crossover by using the "twin-crossover" balanced incomplete block design, which requires that each subject receive only two of the four possible treatments. The "twin crossover" design, coupled with a sequential decision-making process that expedites choosing the doses of the test medication which are most closely equianalgesic with the standard, yielded excellent analgesic assay sensitivity and made efficient use of our population of postoperative patients.