Guidance For Industry - Assessment Of Abuse Potential Of Drugs - U.s. Department Of Health And Human Services - 2017 Page 31
ADVERTISEMENT
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37Contains Nonbinding Recommendations
provide critical information regarding the abuse potential of a test drug. However, in HAP
studies, it is possible to directly correlate the appearance and duration of abuse-related AEs in
relation to responses on VAS subjective measures such as “Drug Liking” and “High”. If specific
abuse-related AEs are reported in earlier clinical studies, HAP study staff should be informed of
the need to increase appropriate monitoring of these AEs, as well as medical or psychiatric
responses, during or after a study session.
A test drug may induce AEs that can modulate subjective measure outcomes or interfere with the
collection of the measures. Examples of such AEs include sedation that prevents data collection
or mobility related to frequent urination that may heighten the subject’s awareness of the effects
of the drug. Considerations should be given in advance regarding how to reduce interruptions to
study procedures because of AEs.
Detailed case narratives for abuse-related AEs should be included with the study report.
Narratives for each AE should include time of onset and duration of the event, dose of drug
taken, severity and outcome. If available, pharmacokinetic values for each individual subject
who experienced these AEs should be provided to determine whether there is a temporal
correlation between drug plasma levels and AEs.
Pharmacokinetic Data
Many HAP studies include an analysis of blood samples collected throughout a study session in
order to monitor drug PK. This is done primarily to confirm that plasma levels of the drug are
equivalent between subjects and to evaluate whether subjective measures and AEs can be
correlated with drug levels over time. Typically, blood is drawn immediately after the collection
of subjective measures is completed at each time point. If an analysis shows that a subject had
low plasma levels of a drug, it may account for a lack of subjective responses in a drug session.
5.
Analysis of Data
The statistical analysis of a HAP study should address whether:
• The known drug of abuse (positive control) produces reliable abuse-related responses
compared to placebo.
• The test drug produces abuse-related responses that are smaller than the positive control.
• The test drug produces abuse-related responses that are similar to placebo.
To address these issues, the following hypotheses should be tested:
1. Validation test of the sensitivity and integrity of the study: Does the positive control (C)
produce mean responses that show greater abuse potential compared to placebo (P)?
Thus, the hypothesis should be tested as following:
µ
µ
δ
µ
µ
δ
−
≤
−
>
δ
>
H
:
H
:
versus
where
.
0
0
C
P
1
a
C
P
1
1
28
ADVERTISEMENT
0 votes
Related Articles
Related forms
Guidance For Industry And Food And Drug Administration Staff - U.s. Department Of Health And Human Services - 2012
Legal
Department Of Health And Human Services Family Medical Leave/family Illness Leave Request Form
Business
Form Nih 2762-3 - Undergraduate Scholarship Program (ugsp) - Academic Enrollment Certification And Service Obligation Deferment Request - U.s. Department Of Health And Human Services
Legal
Form Acf-196t - Administration For Children And Families - U. S. Department Of Health And Human Services
Legal
Related Categories
Parent category: Legal