Article Consideration of Factors Affecting the Safety Index in Early Clinical Drug Development

In drug development, a safety index—the ratio of the highest exposure that does not induce toxicity to the exposure that exerts efficacy—is used to quantify the balance between the safety and efficacy of a test drug. Here, the phase 1 index (maximum area under the curve [AUC] in phase 1/therapeutic AUC) and no-observed-adverse-effect level (NOAEL) index (AUC at NOAEL/ therapeutic AUC) of recently approved drugs in Japan were calculated and characterized by therapeutic areas and indications. A large variation within both indices was observed, with a median of 3.2 for the phase 1 index and 3.5 for the NOAEL index. Furthermore, the safety indices were affected by the therapeutic area, which might be attributed to the difference in unmet med-ical needs for certain diseases. This study provides a qualitative measure for interpreting the phase 1 index versus the NOAEL index and might help inform the decision-making process following phase 1 trials