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Statistical assessment of abuse-deterrent opioids
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Methods: A total of 74 treatment-seeking ketamine dependent patients (mean age: 30.2 ± 5.7 y/o) from Taipei City Psychiatric Center were recruited. Ketamine use was assessed using Time-Line Follow-Back method. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Diagnostic Interview for Genetic Studies were used to evaluate their psychopathology and Visual Analogue Scale (VAS) used for craving. Ketamine use amount and frequency were also investigated. We further dichotomized these patients into depressed and non-depressed group and compared their socio-demographics, psychopathology and ketamine use patterns. Pearson correlation was used to examine the association between craving and depression severity. Results: The average ketamine dose in our patients was 4.5 g/day while the duration of ketamine use was 7.5 ± 4.3 years. 59.5% of them reported moderate to severe depression (BDI > 19) and 42.9% met DSM-IV criteria of current major depression. Comparing subjects with depression to those without, we found the depressed group were less likely to receive college or above education (P = 0.004) and had a greater craving scores (P = 0.006). We also found a strong correlation between craving and depression severity (r = 0.46, P < 0.05). However, there was no association between craving scores and ketamine use frequency (r = −0.09, P > 0.05) or maximum amount (r = 0.19, P > 0.05). Conclusions: We found a high prevalence of depression in treatment-seeking ketamine-dependent patients and craving was associated with depression severity, not with ketamine use patterns. As craving was the major relapse risk factor for ketamine dependence, our finding highlights the significance of treating comorbid depression among ketamine-dependent patients. Financial support: NSC 102-2314-B-182 -007 and CMRPG2D0261. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.121 Statistical assessment of abuse-deterrent opioids Ling Chen FDA/CDER, Silver Spring, MD, United States Aims: In April of 2015, FDA finalized the FDA Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling. In the Statistical Analysis section under the section of Clinical Abuse Potential Studies, the Guidance specifies the unknown abusedeterrent margin ı1 in the primary hypothesis for the comparison of means between crushed, chewed, or otherwise modified test drug (T) and positive control (C) on Drug Liking VAS (bipolar scale), that is, ı1 = ı* (C-50), where C is the mean of C, and 0 < ı* < 1. The actual value of ı1 is related to C. Hence, it may vary according to abuse potential measures and the route of drug administration. For the responder analysis, the Guidance recommends to define a responder as a subject who had at least ı* 100% of reduction, in Emax for T relative to C, and also define the test margin DR% = ı* 100% in the analysis of median percent reduction. Since the Guidance published, questions have arisen on how to perform the primary and secondary analysis with an unknown ı* involved in the primary hypothesis, and in the definition of a responder as well as DR% in the analysis of the median percent reduction. In this presentation, I will give details on how to perform these analyses, and provide a closed testing procedure for obtaining possible better claim than the pre-specified one for the drug label. Conclusions: The recommended statistical methodologies in the 2015 FDA Guidance are applicable, and the results from
the statistical analyses can contribute to an informative drug label. Financial support: N/A. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.122 Smartphone enhanced behavioral activation treatment for substance use and depression Yun Chen 2,∗ , Joseph Anthony De Leo 2 , Laura Matalenas 1 , Anne Collins McLaughlin 1 , Antonio Petruzzella 2 , Elizabeth Jones 2 , Stacey B. Daughters 2 1 Department of Psychology, North Carolina State University, Raleigh, NC, United States 2 Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Aims: The Life Enhancement Treatment for Substance Use (LETS ACT) is a brief behavioral activation treatment for comorbid substance use and depression that has demonstrated effectiveness in improving environmental reward, depressive symptoms and rates of post treatment relapse. We developed a smartphone enhanced LETS ACT to increase the accessibility and quality of treatment engagement outside of clinician administered sessions. Methods: In study 1, 37 substance users (% female; % Caucasian/AA) entering inpatient treatment received standard LETS ACT clinician administered sessions. Participants were randomized to also receive either a smartphone enhanced LETS ACT web-based homework (n = 21), or the standard paper based LETS ACT homework (n = 16). In study 2, a mock smartphone wire-frame was developed and qualitative data was collect from substance users (n = 6) in inpatient treatment. Results: Study 1 data indicated high feasibility and acceptability of the web-based application with high rates of treatment engagement in the experimental group. Further, treatment engagement was associated with 1-month post-treatment abstinence among experimental participants, but not control participants. In study 2, user experience data informed application functions that need further iteration, such as simplicity in user interface, timely reminders, and effective gamification strategies. Conclusions: With a few limitations, preliminary studies demonstrated the feasibility and acceptability of smartphone technology in extending the accessibility and quality of treatment engagement outside of clinician administered sessions. These data informed the development of a highly-functional smartphone application for LETS ACT. Financial support: R01 DA026424. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.123 Male–female differences of antecedent cannabis use among newly incident young alcohol drinkers: Does age matter? Hui G. Cheng 1,∗ , Catalina Lopez-Quintero 1 , James C. Anthony 2 1 Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States 2 Michigan State University, East Lansing, MI, United States
Aims: We study cannabis use that predates onset of drinking, and estimate sex-, age-, and cohort-specific proportions of newly
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Methods: A total of 74 treatment-seeking ketamine dependent patients (mean age: 30.2 ± 5.7 y/o) from Taipei City Psychiatric Center were recruited. Ketamine use was assessed using Time-Line Follow-Back method. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Diagnostic Interview for Genetic Studies were used to evaluate their psychopathology and Visual Analogue Scale (VAS) used for craving. Ketamine use amount and frequency were also investigated. We further dichotomized these patients into depressed and non-depressed group and compared their socio-demographics, psychopathology and ketamine use patterns. Pearson correlation was used to examine the association between craving and depression severity. Results: The average ketamine dose in our patients was 4.5 g/day while the duration of ketamine use was 7.5 ± 4.3 years. 59.5% of them reported moderate to severe depression (BDI > 19) and 42.9% met DSM-IV criteria of current major depression. Comparing subjects with depression to those without, we found the depressed group were less likely to receive college or above education (P = 0.004) and had a greater craving scores (P = 0.006). We also found a strong correlation between craving and depression severity (r = 0.46, P < 0.05). However, there was no association between craving scores and ketamine use frequency (r = −0.09, P > 0.05) or maximum amount (r = 0.19, P > 0.05). Conclusions: We found a high prevalence of depression in treatment-seeking ketamine-dependent patients and craving was associated with depression severity, not with ketamine use patterns. As craving was the major relapse risk factor for ketamine dependence, our finding highlights the significance of treating comorbid depression among ketamine-dependent patients. Financial support: NSC 102-2314-B-182 -007 and CMRPG2D0261. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.121 Statistical assessment of abuse-deterrent opioids Ling Chen FDA/CDER, Silver Spring, MD, United States Aims: In April of 2015, FDA finalized the FDA Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling. In the Statistical Analysis section under the section of Clinical Abuse Potential Studies, the Guidance specifies the unknown abusedeterrent margin ı1 in the primary hypothesis for the comparison of means between crushed, chewed, or otherwise modified test drug (T) and positive control (C) on Drug Liking VAS (bipolar scale), that is, ı1 = ı* (C-50), where C is the mean of C, and 0 < ı* < 1. The actual value of ı1 is related to C. Hence, it may vary according to abuse potential measures and the route of drug administration. For the responder analysis, the Guidance recommends to define a responder as a subject who had at least ı* 100% of reduction, in Emax for T relative to C, and also define the test margin DR% = ı* 100% in the analysis of median percent reduction. Since the Guidance published, questions have arisen on how to perform the primary and secondary analysis with an unknown ı* involved in the primary hypothesis, and in the definition of a responder as well as DR% in the analysis of the median percent reduction. In this presentation, I will give details on how to perform these analyses, and provide a closed testing procedure for obtaining possible better claim than the pre-specified one for the drug label. Conclusions: The recommended statistical methodologies in the 2015 FDA Guidance are applicable, and the results from
the statistical analyses can contribute to an informative drug label. Financial support: N/A. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.122 Smartphone enhanced behavioral activation treatment for substance use and depression Yun Chen 2,∗ , Joseph Anthony De Leo 2 , Laura Matalenas 1 , Anne Collins McLaughlin 1 , Antonio Petruzzella 2 , Elizabeth Jones 2 , Stacey B. Daughters 2 1 Department of Psychology, North Carolina State University, Raleigh, NC, United States 2 Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Aims: The Life Enhancement Treatment for Substance Use (LETS ACT) is a brief behavioral activation treatment for comorbid substance use and depression that has demonstrated effectiveness in improving environmental reward, depressive symptoms and rates of post treatment relapse. We developed a smartphone enhanced LETS ACT to increase the accessibility and quality of treatment engagement outside of clinician administered sessions. Methods: In study 1, 37 substance users (% female; % Caucasian/AA) entering inpatient treatment received standard LETS ACT clinician administered sessions. Participants were randomized to also receive either a smartphone enhanced LETS ACT web-based homework (n = 21), or the standard paper based LETS ACT homework (n = 16). In study 2, a mock smartphone wire-frame was developed and qualitative data was collect from substance users (n = 6) in inpatient treatment. Results: Study 1 data indicated high feasibility and acceptability of the web-based application with high rates of treatment engagement in the experimental group. Further, treatment engagement was associated with 1-month post-treatment abstinence among experimental participants, but not control participants. In study 2, user experience data informed application functions that need further iteration, such as simplicity in user interface, timely reminders, and effective gamification strategies. Conclusions: With a few limitations, preliminary studies demonstrated the feasibility and acceptability of smartphone technology in extending the accessibility and quality of treatment engagement outside of clinician administered sessions. These data informed the development of a highly-functional smartphone application for LETS ACT. Financial support: R01 DA026424. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.123 Male–female differences of antecedent cannabis use among newly incident young alcohol drinkers: Does age matter? Hui G. Cheng 1,∗ , Catalina Lopez-Quintero 1 , James C. Anthony 2 1 Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States 2 Michigan State University, East Lansing, MI, United States
Aims: We study cannabis use that predates onset of drinking, and estimate sex-, age-, and cohort-specific proportions of newly