Implementation of Consistent Language as Outlined in FDA Draft Guidance on Drug Abuse and Dependence Labeling Will Support Drug Development, Labeling and Prescriber Decision-Making

Categories: Abuse Potential Assessment, FDA, Postmarketing Surveillance, Risk Management

By Jack Henningfield, Karen Gerlach, Judy Ashworth, Marion Coe, Sid Schnoll

Once finalized, FDA Draft Guidance “Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products — Content and Format” will help ensure more consistent language across drug products about abuse, misuse, addiction, dependence, and tolerance. Our experts in the development and evaluation of drugs with abuse potential, and post-marketing risk management for controlled substances submitted comments to the FDA (read more here) about the proposed definitions for abuse, addiction, physical dependence and withdrawal.

To support drug development, and clinical and regulatory strategy, drug developers would benefit from using the proposed definitions from the beginning of drug development to the development of the label.  During development, consistent language will facilitate the collection and characterization of appropriate data in clinical trials and clear communications with FDA when input is needed to guide the development strategy.  Further, consistent use of these definitions in drug labeling will help prescribers communicate the risks to their patients to minimize the occurrence and risk of substance-use related problems and those related to withdrawal and physical dependence.

Our experts’ comments encompassed the following:

 Physical Dependence and Withdrawal. Withdrawal symptoms are hallmark measures for determining physical dependence and are part of the pharmacology of many drugs regardless of whether the drug is considered to carry significant abuse potential. However, withdrawal symptoms by themselves are not sufficient to conclude that the patient is “addicted”, has developed a “dependency” or “or substance use disorder” by criteria of the American Psychiatric Association’s DSM-5 or World Health Organization’s ICD-10  The inappropriate conflating of withdrawal symptoms with “abuse” and “addiction” has led to the misunderstanding of the meaning and relevance of withdrawal. This can impact treatment decisions by healthcare professionals and safe and effective use of prescribed medicines by patients.

For drug developers, assessing the nature of the symptoms of physical dependence should encompass systematic collection and assessment of adverse events Clinical and non-clinical studies should be designed to determine if physical dependence symptoms occur with drug administration (per 2017 Guidance for Industry Assessment of the Abuse Potential of Drugs).

Abuse Potential.  FDA’s 2017 Abuse Potential Guidance describes the data needed for most aspects of the label to address the abuse potential, development of physical dependence, and withdrawal signs and symptoms. This new draft guidance on Drug Abuse and Dependence complements the 2017 Abuse Potential Guidance by proposing the approach by which labeling may include information, data, and study findings relevant to abuse potential.

Labeling on abuse may help differentiate drugs within the same schedule of the Controlled Substances Act This differentiation can be invaluable to health professionals making decisions about which drugs might be most appropriate for a particular patient (Dasgupta, Henningfield, Ertischek and Schnoll, 2011).

Addiction. Addiction is the most commonly used lay term for what is technically termed Substance Use Disorder (SUD) in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and Dependence in the World Health Organization’s International Classification of Diseases, tenth edition (WHO ICD-10).  In practice, the term addiction is used by the lay public for relatively benign substance use behaviors such as daily caffeine intake, daily consumption of a serving of wine or beer with dinner as well as for life-threatening alcohol, opioid and cocaine patterns of use.

Thus, our experts suggest that FDA make clear that its proposed definition of addiction is not intended to replace SUD, nor does it imply a subset of SUD for diagnostic, therapeutic, or medical disease coding for insurance purposes. Rather ‘addiction’ is a term that is widely used in general communications and warnings, much as other general terms when technical language might be less impactful and less generally understood, e.g., cancer, heart attack, kidney disease, and overdose.

Once finalized, the specific definitions and terminology established by FDA for use in prescription labeling will support harmonized labeling regarding abuse, misuse, addiction, physical dependence, and tolerance. Labeling that conveys more accurate information about these topics is important for patients, prescribers, caregivers and families, as well as pharmaceutical developers. It is also among the many steps needed to more effectively minimize the occurrence and risks of substance use related problems for individual patients and at the societal level.

You can read our comment to the FDA in its entirety here.