Shortening the Timeline of Pediatric Phase I Trials: The Rolling Six Design

@article{citeulike:2212318, abstract = {PurposeTo shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design. MethodsA comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients concurrently onto a dose level based on the number of patients currently enrolled and evaluable, the number experiencing dose-limiting toxicity (DLT), and the number still at risk of developing a DLT. Clinical trial simulations (n = 1,000) were based on historical data and were performed using SAS 9.1.3 (SAS Institute, Cary, NC). Study timelines and patient numbers were determined for each design, and safety was assessed as a function of the number of DLTs observed. ResultsIn twelve completed historical studies, the median time to study completion was 452 days (range, 220 to 606 days); number of evaluable participants enrolled was 22 (range, 11 to 33), and DLTs occurring per study was three (range, 0 to 5). In 1,000 study simulations, in which the average time to new patient accrual was 10 days, the average {+/-} standard deviation (SD) time to study completion was 294 {+/-} 75 days for the rolling six design versus 350 {+/-} 84 days for the 3 + 3 design, whereas the number of DLTs per study was the same (average {+/-} SD, 3.3 {+/-} 1.1 v 3.2 {+/-} 1.1 for the rolling six and 3 + 3 designs, respectively). ConclusionThe rolling six design may significantly decrease the duration of pediatric phase I studies without increasing the risk of toxicity. The design will be tested prospectively in upcoming Children's Oncology Group phase I trials. 10.1200/JCO.2007.12.7712}, author = {Skolnik, Jeffrey M. and Barrett, Jeffrey S. and Jayaraman, Bhuvana and Patel, Dimple and Adamson, Peter C. }, citeulike-article-id = {2212318}, doi = {http://dx.doi.org/10.1200/JCO.2007.12.7712}, journal = {J Clin Oncol}, keywords = {ab\_design, clinical\_trial, pediatric, phase\_i}, month = {January}, number = {2}, pages = {190--195}, posted-at = {2008-01-09 22:29:45}, priority = {2}, title = {Shortening the Timeline of Pediatric Phase I Trials: The Rolling Six Design}, url = {http://dx.doi.org/10.1200/JCO.2007.12.7712}, volume = {26}, year = {2008} }

TY - JOUR ID - citeulike:2212318 L3 - citeulike-article-id:2212318 N2 - PurposeTo shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design. MethodsA comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients concurrently onto a dose level based on the number of patients currently enrolled and evaluable, the number experiencing dose-limiting toxicity (DLT), and the number still at risk of developing a DLT. Clinical trial simulations (n = 1,000) were based on historical data and were performed using SAS 9.1.3 (SAS Institute, Cary, NC). Study timelines and patient numbers were determined for each design, and safety was assessed as a function of the number of DLTs observed. ResultsIn twelve completed historical studies, the median time to study completion was 452 days (range, 220 to 606 days); number of evaluable participants enrolled was 22 (range, 11 to 33), and DLTs occurring per study was three (range, 0 to 5). In 1,000 study simulations, in which the average time to new patient accrual was 10 days, the average {+/-} standard deviation (SD) time to study completion was 294 {+/-} 75 days for the rolling six design versus 350 {+/-} 84 days for the 3 + 3 design, whereas the number of DLTs per study was the same (average {+/-} SD, 3.3 {+/-} 1.1 v 3.2 {+/-} 1.1 for the rolling six and 3 + 3 designs, respectively). ConclusionThe rolling six design may significantly decrease the duration of pediatric phase I studies without increasing the risk of toxicity. The design will be tested prospectively in upcoming Children's Oncology Group phase I trials. 10.1200/JCO.2007.12.7712 IS - 2 JF - J Clin Oncol EP - 195 TI - Shortening the Timeline of Pediatric Phase I Trials: The Rolling Six Design VL - 26 SP - 190 KW - ab_design KW - clinical_trial KW - pediatric KW - phase_i AU - Skolnik, Jeffrey AU - Barrett, Jeffrey AU - Jayaraman, Bhuvana AU - Patel, Dimple AU - Adamson, Peter PY - 2008/01/10/ UR - http://dx.doi.org/10.1200/JCO.2007.12.7712 ER -