TY - JOUR
KW - Abuse-Deterrent Formulations/statistics & numerical data
KW - Analgesics, Opioid/therapeutic use
KW - Data Interpretation, Statistical
KW - Humans
KW - Opioid-Related Disorders/drug therapy
KW - abuse-deterrent formulation
KW - clinical abuse potential study
KW - closed testing procedure
KW - gatekeeping testing procedure
KW - opioid product
AU - L. Chen
A1 - 
AB - The FDA Guidance for Industry: Abuse-Deterrent Opioids-Evaluation and Labeling was published in April 2015. Since then questions have been raised regarding how to determine the relative abuse-deterrent (AD) effect of an AD formulation (a test product) compared to an immidiate release (IR) or NonAD extended release (ER) formulation of the same opioid (a positive control) and how to define a responder for responder analysis in clinical abuse potential studies. These questions are reasonable and important for the assessment of AD effect of an AD formulation. This article discusses the principles of the statistical assessment in this area and gives details on how to calculate sample size for the primary comparison in the study and how to perform the statistical analyses. In addition, the article also discusses the reason why the non-inferiority test is not proper for the comparison between a test product and an approved AD version of the same opioid product. Finally, a gatekeeping testing procedure is proposed for this comparison with an example.
AD - Division of Biometrics VI, Office of Biostatistics, Office of Translational Science, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
BT - Therapeutic innovation & regulatory science
C5 - Opioids & Substance Use
CP - 1
CY - United States
DO - 10.1177/2168479017710062
IS - 1
JF - Therapeutic innovation & regulatory science
M1 - Journal Article
N2 - The FDA Guidance for Industry: Abuse-Deterrent Opioids-Evaluation and Labeling was published in April 2015. Since then questions have been raised regarding how to determine the relative abuse-deterrent (AD) effect of an AD formulation (a test product) compared to an immidiate release (IR) or NonAD extended release (ER) formulation of the same opioid (a positive control) and how to define a responder for responder analysis in clinical abuse potential studies. These questions are reasonable and important for the assessment of AD effect of an AD formulation. This article discusses the principles of the statistical assessment in this area and gives details on how to calculate sample size for the primary comparison in the study and how to perform the statistical analyses. In addition, the article also discusses the reason why the non-inferiority test is not proper for the comparison between a test product and an approved AD version of the same opioid product. Finally, a gatekeeping testing procedure is proposed for this comparison with an example.
PP - United States
PY - 2018
SN - 2168-4804; 2168-4790
SP - 7
EP - 13
EP - 
T1 - Principles and Methods of Statistical Assessment of Abuse-Deterrent Opioids
T2 - Therapeutic innovation & regulatory science
TI - Principles and Methods of Statistical Assessment of Abuse-Deterrent Opioids
U1 - Opioids & Substance Use
U2 - 29714622
U3 - 10.1177/2168479017710062
VL - 52
VO - 2168-4804; 2168-4790
Y1 - 2018
Y2 - Jan
ER -