Contains Nonbinding Recommendations
Draft — Not for Implementation
Clinical Trial Data Relative to Abuse Potential Assessments
688 The evaluation of the adverse events profile of a drug from clinical trials can provide a signal of
689 abuse potential. The systematic categorization, tabulation, and analysis of safety data for mood
690 elevation, sedation, and psychotomimetic events can provide useful information. The incidence
691 of euphoria-type adverse events (including euphoria, euphoric mood, elevated mood, mood
692 alteration, feeling drunk, feeling abnormal) and hallucination (visual and auditory) are a few of
693 the more prominent MedDRA terms that should be considered. MedDRA 12 terms for
694 inappropriate affect, which include the following lower level terms: elation inappropriate,
695 exhilaration inappropriate, feeling happy inappropriately, inappropriate affect, inappropriate
696 elation, inappropriate laughter, inappropriate mood elevation, should also be considered. A
697 prospective evaluation of withdrawal adverse events after abrupt discontinuation of treatment
698 can provide information relevant to dependence. Various quantitative measurements will be
699 useful in providing objective data to assess dependence (e.g., opioid and benzodiazepine
700 withdrawal scales and psychiatric rating scales). Data related to serious psychiatric and
701 neurological adverse events and the need for hospitalization is relevant to the public health risks
702 and abuse potential of the drug.
704 Phase 3 clinical trials evaluate the safety and efficacy of a product for a specific condition in
705 large multi-center trials involving the intended patient populations. Phase 3 trials provide
706 support for therapeutic dose recommendations; dose response data; and data relevant to abuse,
707 dependence potential, drug diversion, and accountability, as related to study subjects (completers
708 and dropouts).
709 Sponsors should make every effort to do the following:
1. Set criteria, collect data, and tabulate the abuse, misuse, noncompliance, and diversion
cases across the studies and study sites with special attention to aberrant drug behaviors
that may be indicative of drug abuse, misuse and/or diversion.
2. Provide complete information, including case report forms and final outcomes, on all
instances of addiction, abuse, misuse, overdose, drug diversion/drug accountability,
discrepancies in amount of the clinical supplies of the study drug, noncompliance,
protocol violations, lack of efficacy, individuals lost to follow-up, and any other reasons
why subjects dropped out of the study.
3. Provide information on the risks of addiction, abuse, misuse, overdose, and drug
diversion in the study populations.
724 Pertinent data can include measurements of drug accountability, tolerance, physical dependence,
725 or withdrawal symptoms, and the presence of signs or symptoms of drug abuse, misuse,
S.D. Passik, K.L. Kirsh, K.B. Donaghy, R.K. Portenoy, “Pain and Aberrant Drug-Related Behaviors in Medically
Ill Patients With and Without Histories of Substance Abuse,” in
, 2(2):173-81, Feb 2006.
http://sbirt.samhsa.gov/ Screening and brief intervention (SBI) can identify the severity of the “problem” in study
participant and identify the appropriate level of intervention.