TY - JOUR
T1 - Observations on three endpoint properties and their relationship to regulatory outcomes of European oncology marketing applications
AU - Liberti, Lawrence
AU - Stolk, Pieter
AU - McAuslane, James Neil
AU - Schellens, Jan
AU - Breckenridge, Alasdair M.
AU - Leufkens, Hubert
PY - 2015
Y1 - 2015
N2 - Background. Guidance and exploratory evidence indicate that the type of endpointsand the magnitude of their outcome can define a therapy’s clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. Materials and Methods.We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Results. Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments.There was no difference (p =.3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p
AB - Background. Guidance and exploratory evidence indicate that the type of endpointsand the magnitude of their outcome can define a therapy’s clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. Materials and Methods.We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Results. Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments.There was no difference (p =.3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p
KW - Accelerated approvals
KW - Endpoints
KW - Marketing authorization application
KW - Oncology
KW - Overall survival
KW - Progression-free survival
UR - http://www.scopus.com/inward/record.url?scp=84933038474&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2014-0297
DO - 10.1634/theoncologist.2014-0297
M3 - Article
AN - SCOPUS:84933038474
SN - 1083-7159
VL - 20
SP - 683
EP - 691
JO - Oncologist
JF - Oncologist
IS - 6
ER -