Report recommends re-designating new opioid formulations as “tamper-resistant;” recognizes role in clinical practice, but advises cautious consideration of the financial and public health impact of broad substitution mandates– 

Boston, Mass., August 8, 2017 – A Final Evidence Report from the Institute of Clinical and Economic Review (ICER), containing evidence analyses and the results of voting by an independent appraisal committee, concludes that existing evidence is not adequate to demonstrate that abuse-deterrent formulations (ADFs) of opioids are effective in reducing overall abuse of opioids at a population level.  The report reviewed nine extended release ADFs and one immediate release formulation.  It was subject to public deliberation and voting during a meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC) on July 20, 2017. An accompanying Report-at-a-Glance provides a brief summary of the report’s key findings.

For several years, manufacturers have been working to produce opioids that are more difficult to crush, snort, or inject. The most common route of opioid abuse, however, is swallowing more pills. ICER’s report found very little evidence on the impact of ADFS on abuse in clinical practice, and there is some evidence suggesting that ADFs can lead those trying to abuse the drug to switch to other, potentially more dangerous drugs, including heroin and fentanyl.

“Those opioid formulations today being identified as “abuse-deterrent” – which our report suggests should more accurately be called “tamper-resistant” — will certainly be part of broader strategies to combat the opioid epidemic,” said Dan Ollendorf, PhD, ICER’s Chief Scientific Officer.  “However, while some evidence suggests that prescribing OxyContin, the first opioid to be produced in ADF form, did reduce the abuse risk among individual patients and decreased diversion of the drug into other hands, the New England CEPAC voted that the evidence is not sufficient to demonstrate that it or other ADF opioids are effective in reducing overall abuse of opioids on a population level.”

Discussion among clinical experts and others at the public meeting noted the tension between the potential benefits of ADF opioids and the complex outcomes that might occur with the removal of non-ADF opioids.  “While we would like to support widespread use of a product that may lower the abuse risk for individual patients, policies that mandate replacement of non-ADF opioid prescriptions with ADFs may have the unintended consequences of opioid users shifting abuse to other opioids or heroin, which may ultimately result in increased harm.  We need more evidence to fully understand the impact such policies will have,” noted Jeanmarie Perrone, MD, Professor of Emergency Medicine and Director of Medical Toxicology in the Department of Emergency Medicine at the Perelman School of Medicine at the University of Pennsylvania.

The ICER report also examined the potential costs that would accompany legislation being considered by many states to encourage rapid replacement of all non-ADF opioids with more expensive ADFs.  ICER’s report finds that, at current price premiums for ADFs, broad substitution would create substantial health care cost increases that could prove unaffordable for many health systems and also divert resources needed for other efforts to address the opioid crisis.

“The potential budget impact of these drugs has to be taken into consideration when thinking about mandating widespread use,” noted C. Bernie Good, MD, MPH, Chair of the Medical Advisory Panel for Pharmacy Benefits Management in the Department of Veterans Affairs. “We want to encourage innovation that may help to deter opioid abuse, but without significant discounts to the current prices, widespread or mandated use of ADF opioids will drive up costs for patients and the health system at an unsustainable rate.”

Analyses in ICER’s report estimated that, for every 100,000 individuals prescribed an extended-release ADF opioid, there would be a net $533 million increase in costs over five years. This estimate includes an assumption that ADFs reduce abuse and produce savings in abuse-related inpatient and outpatient costs, but these cost savings were outweighed by a much larger increase in prescription costs.  However, according to ICER analyses, abuse-deterrent opioids could have an average price premium of 18% above non-ADF versions and be cost-neutral within the health system, although these analyses did not consider the lowered costs of reduced diversion or increased costs associated with switching to other opioids.

Policy Recommendations
ICER’s final report includes policy recommendations to provide guidance to stakeholders faced with decisions on implementation of ADFs. The recommendations include:
  • The term “abuse-deterrent formulation” is confusing for prescribers, patients, and the public, contributing to a significant risk that the addictive and abuse potential of ADFs will be misunderstood.  The FDA should reconsider whether it can use the term “tamper-resistant formulation.”
  • ADFs should have a growing role in clinical practice since evidence suggests that they are safer for the individual patient. Still, policymakers should be aware that there is some evidence that demonstrates shifts in abuse towards other illicit drugs following introduction of ADFs. As a result, mandatory ADF substitution laws may cause more harm to the overall population, and policymakers and clinical leaders should consider measures to phase in ADFs while ensuring adequate support for other arms of a multi-pronged approach to the opioid crisis.
  • Manufacturers and payers must recognize a shared commitment to making ADFs affordable to patients and to the health system.  Manufacturers should moderate the exercise of monopoly pricing power, and payers should accept paying a premium for ADFs and reduce barriers such as increased out of pocket payments.
  • The federal government should convene clinical experts, clinical pharmacists, patients, and payers to develop consistent methods to identify patients whose environment represents a high risk for the abuse of opioids.
  • Public health policymakers at the federal level should educate the public about the risks of all opioids through a major public health campaign, perhaps modeled on the techniques employed nationally to reduce smoking.
To see the full list of ICER’s policy recommendations, along with additional explanation, please see ICER’s full report.
About ICER
The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.
ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.