Discover this groundbreaking webinar delving into the latest insights from the Cross-Company Abuse Liability Council (CCALC) and The Food and Drug Administration (FDA) in drug development and clinical evaluation of human drug abuse and dependence potential. This webinar aims to discuss current knowledge and recent updates on the clinical evaluation of the abuse and dependence potential of drugs. In September 2023, the CCALC, a group of representatives from the industry, held its first face-to-face meeting with members of the Controlled Substances Staff of The FDA since 2018. At this meeting, key opinion leaders discussed nonclinical and clinical assessments, current issues in the design and analysis of these studies and pertinent topics that have emerged based on recent trends in drug development (e.g., hallucinogens). The clinical portion of the meeting discussed a broad range of topics; however, the current webinar will focus on updating attendees on:

    1. Discussions relating to the design and statistical analysis of human abuse potential (HAP) studies
    2. Challenges related to recording and documenting abuse-related adverse events
    3. Regulatory requirements for assessing physical dependence and withdrawal within a clinical program

    The abuse and dependence potential assessment of a new molecular entity requires a comprehensive evaluation of both the nonclinical and clinical effects of the drug. In January 2017, The FDA released a final guidance on the evaluation of the abuse potential of drugs that included detailed guidelines on requirements for nonclinical and clinical assessments, as well as information related to the methodology of conducting a HAP study.

    HAP studies are randomized crossovers evaluating multiple dose levels of the new chemical entity (NME), positive control(s) with known abuse potential and placebo, using a range of subjective effects measures administered at multiple time points. Their designs include an enriched sample of “experienced recreational drug users”, as well as highly sensitive endpoints (“canary in the coalmine” approach). These safety studies are often geared towards excluding false negatives (i.e., concluding no abuse potential, when it exists), usually at the expense of false positive results (concluding abuse potential when there isn’t any).

    Non-linear dose responses (inverted U-shape) associated with drugs of abuse can present challenges in interpretation, as can the variability and “distributional” violations associated with the subjective measures. These factors can make the analysis and interpretation of these data difficult.