Effectiveness and framing of pharmaceutical opioid abuse-deterrent formulations

Summary:

Abuse-deterrent formulations (ADFs) of pharmaceutical opioids have limited capacity to reduce extra-medical use and harm; their impact is likely restricted to prevention of specific practices among population sub-groups. This debate highlights the importance of viewing ADFs as one component in a range of public health responses. Greater involvement of invested parties (e.g., prescribers, consumers) and reframing terminology will reduce discrimination and stigma.

Commentary:

We proposed a series of best practice recommendations for study methods, conduct, design and governance for evaluating the real-world impact of so-called ‘abuse-deterrent formulations’ (ADFs; ¹) in reducing pharmaceutical opioid extra-medical use and harms (2). The authors providing commentary on our framework (3–5) have raised insightful and valuable points in relation to the latter, with three common and intertwined themes that we explore further here.

The first theme relates to ADF effectiveness in reducing pharmaceutical opioid extra-medical use and harm. Both Jauncey (5) and Humphreys (3) reinforce our argument for measuring effectiveness using various outcomes, the former stating that ADFs must reduce the overall experience of harm (in addition to reducing specific aspects of extra-medical use) and the latter stating that ADFs may produce temporally-variable and different impacts across outcomes. Indeed, we contend that evidence of effectiveness needs to be weighed across a matrix of possible outcomes, time-points (e.g., short versus long-term) and populations (e.g., general population versus sentinel groups) (6).

As Nelson (4) rightly points out, the value of ADFs must also be considered in conjunction with, and in comparison to, alternative strategies to reduce pharmaceutical opioid-related harms. A major problem is the poor documentation of opioid harms; ICD-10/11 coding of both hospital admissions and deaths does not specify the specific opioid, route of administration or specific other contributing drugs. The proportion of harms due to injection of the relevant opioids is not known at a population level. However, many people prescribed opioids for pain do not engage in extra-medical use; of those who do, the most common behaviour is consuming a greater dose than recommended (7). Thus, ADFs are a costly intervention with minimal impact if used widely in all patients (8). Increased opioid-related mortality has arisen in part through overprescribing, but also as a result of serious economic and social disadvantage (9). Moving beyond approaches aimed at reducing opioid supply or changing the opioid market is critical, particularly when other strategies (e.g., access to opioid substitution therapy, naloxone availability) can positively impact a broader group but have not been scaled up, and when strategies which perpetuate harms (e.g., heavy prison sentences for drug-related crimes) continue to abound (10).

The second theme across the commentaries relates to the critical role of education about the risk-benefit profile of ADFs for prescribers, people working in pain management, in drug treatment services (3, 4), and in other harm reduction services.(5). Better education about ADFs could reduce discrimination against people with substance dependence requiring analgesia for pain, and ensure consumers are accurately informed about the risks of ADFs when used as prescribed or when attempting to circumvent ADF technology (3). We also agree with Jauncey (5) that meaningful involvement of people with lived experience of drug use must be gold standard practice with respect to development and evaluation of ADFs. We believe this also applies to the planning and evaluation of the full range of interventions to reduce pharmaceutical opioid harms, with consideration as to different modes of engagement for consumers that maximises their involvement (11).

The third theme relates to language choice, both specific to ADFs and within broader discussion of other responses to problematic use pharmaceutical opioid and harms. In our manuscript (2), we purposefully refrained from using the term ‘abuse’ except where referring to nomenclature used by the US Food and Drug Administration (i.e., ‘abuse deterrent formulation’; 1). We used the term ‘extra-medical use’, comprising use outside the bounds of a doctor’s prescription; this includes use without a doctor’s prescription or not as directed by a doctor, and does not exclude the possibility that a person may have a medically-driven reason for using the medication (12). As highlighted by Jauncey (5), use of the term ‘abuse’ to describe behaviours targeted by ADFs is stigmatising. We would also argue that use of the term ‘deterrence’ has additional moralistic connotations, typically being defined as the prevention of an outcome through the presence of a threat, and suggesting use is purely individually-motivated (ignoring structural drivers of use). We agree ‘abuse-deterrent’ can easily be misinterpreted, or misrepresented in marketing. There is clearly scope to revisit nomenclature in this field, which might be considered by the US Food and Drug Administration and other agencies. Significant attention on interventions to reduce opioid-related mortality in various countries serves as a unique opportunity to reframe discourse, and use language which supports strategies for positive health outcomes, and discourages punitive strategies (13).