Overall success rate of a safe and efficacious drug: Results using six phase 1 designs, each followed by standard phase 2 and 3 designs.

ABSTRACT: To evaluate the overall success rate of a new drug, phase 1, 2, and 3 trials were simulated using eight toxicity and two non-decreasing efficacy profiles. Six phase 1 designs including the standard 3 + 3, CCD, BOIN, mTPI, mTPI-2, and CRM were considered with standard phase 2 and 3 designs. Based on our results, phase 1 design recommendations are provided when data informing the general shape of the dose-toxicity curve exist. If a large jump in toxicity between dose levels is expected, the standard 3 + 3 design is recommended; it more often recognized when the MTD was exceeded and had the highest overall success rates. If gradually increasing toxicity is expected, a nonstandard design other than the CRM is recommended. Nonstandard designs were more aggressive in dosing and MTD estimation th

SUBMITTER: Ruppert AS 

PROVIDER: S-EPMC6139598 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature