In vivo drug‐drug interaction studies‐ A survey of all new molecular entities approved from 1987 to 1997

Ninety‐eight new molecular entities applications approved between 1987 to 1991 (period I) and 193 applications for new molecular entities between 1992 to 1997 (period II) were surveyed for drug‐drug interaction studies. In period I (used as a comparator), 32 applications contained drug‐drug interaction studies for a total of 117 studies. In period II, 106 applications reported drug‐drug interaction studies, and the number of studies per new molecular entity ranged from 0 to 15. Most studies (77%) were performed in healthy subjects, with 44% using crossover designs, 7% using parallel designs, and the remaining using fixed sequence designs. The most common dosing scheme for new molecular entities/interacting drug was multiple dose (47%), whereas single dose/multiple dose was used in 31% of studies, and single dose/single dose was used in 18% of studies. Of the 540 drug‐drug interaction studies submitted in period II, 80 (15%) resulted in clinically significant labeling statements. Submissions for new molecular entities to the Center for Drug Evaluation and Research divisions most likely to include drug‐drug interaction studies were neuropharmacology, cardiorenal, antiviral, and antiinfective drugs. Some drug classes such as oncology drug products and radioimaging products were least likely to include drug‐drug interaction studies in their submissions. We conclude that the use of drug‐drug interaction studies in the drug development process has increased between the two periods.