Issue 19: Analysis of FDA's October Advisory Committee Meeting


	October/November 2010 \| ISSUE 19

	Welcome to the NAVIPPRO Signal. On October 21-22, the FDA held a “Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee” in Washington, D.C. At the meeting, the FDA Advisory Committee offered feedback and guidance to the FDA for post-marketing studies aimed at proving that certain new formulations of prescription opioids decrease the capacity for abuse or tampering. Details and information about questions posed at the meeting are available here. We hope this issue of NAVIPPRO Signal is useful. If you have any questions about NAVIPPRO or our research, please feel free to contact us. Sincerely, The NAVIPPRO team Back to top Analysis of FDA’s Advisory Committee on prescription opioid post-marketing studies Purdue Pharma LP and King Pharmaceuticals Inc. each proposed a series of post-marketing studies designed to look at different data streams and get an overall picture of the effects of new so-called “tamper-resistant” opioid medications which are currently, or will soon be marketed. Purdue has released a new formulation of OxyContin© which they believe is likely to be a tamper-resistant formulation (TRF). King Pharmaceuticals produced its own new product, EMBEDA®, a form of morphine sulfate which they believe is an abuse-deterrent formulation (ADF). (To date, the terms TRF and ADF have been used almost interchangeably. Although the Advisory Committee discussed which term is preferable, no decision was forthcoming.) King and Purdue both offered prescription drug abuse data captured by Inflexxion’s proprietary NAVIPPRO® data streams, which include abuse treatment center data from ASI-MV Connect®, Comprehensive Health Assessment for Teens (CHAT®) and internet monitoring data from Web Informed Services (WIS®). Several members of the NAVIPPRO research team were on hand at the Committee meeting to present or answer questions for each company. The proposed post-marketing studies are designed to assess the known serious risks of these products and whether product-specific properties, intended to deter tampering and subsequent abuse by alternative routes of administration (such as snorting, chewing and injecting), actually result in a decrease in the risks and consequences of this type of abuse. “The main conclusion that can be drawn from the meeting is that any company seeking an ‘abuse-deterrent’ or ‘tamper-resistant’ label is going to be required to have a series of epidemiological studies in place and collect data to support their contentions,” said Simon Budman, PhD, founder and CEO of Inflexxion and co-founder of NAVIPPRO. Budman added that the crux of these studies would be largely focused on lessening the use of the drug through routes of administration besides taking the drug orally by swallowing whole. Any opioid medication other than a transdermal patch must have the capacity to be used orally, but abusers often use alternative routes in order to achieve a better or faster “high.” Data from the NAVIPPRO system, for example, will be able to help determine if and how the new King and Purdue products are being used by alternatives routes compared to products without tamper resistance. A majority of the studies proposed by each company were based on proprietary data streams rather than publically available data. Both companies used NAVIPPRO data collected from substance abuse treatment clinics and internet monitoring, as well as RADARS® data from poison control centers. Presenters from the FDA, CDC, and other organizations said this data should be utilized because it provides background and information that publicly available data streams cannot. For example, proprietary data streams are able to provide data in near-real time, while public data may take years before any meaningful data becomes apparent. Although the FDA Advisory Committee did not commit to any single data stream or epidemiological approach, they believe using a multitude of studies and sources is the correct way to proceed. “The FDA has really come around on the value of internet monitoring and proprietary data,” said Budman. “These are sources of data that are timelier and more product specific than most of the public government supported systems.” NAVIPPRO data are collected at participating treatment centers each time a new patient is admitted. The data from each individual patient assessment is uploaded in real time to a central data center. These patient-level data are aggregated and analyzed by NAVIPPRO epidemiologists and research staff to detect patterns of abuse among the population. While Purdue stated it is not currently seeking “tamper-resistant” labeling for the new formulation of OxyContin© (an objective of the King proposed program), the FDA is open to such labeling, but data would need to be collected for at least three to five years or longer before these types of conclusions can be made and put on the label. The FDA continues to remain cautious about these issues, but has been dealing with them more and more as many companies are seeking to market new opioid formulations with ADF or TRF labeling. The Advisory Committee members did express some concerns during the meeting about whether these new formulations would have an impact on prescription practices of the drug, or whether an opioid abuser would simply move on to another, easily available non-abuse deterrent formulation. For now, the FDA seems to have provided guidance that can be useful for other opioid manufacturers seeking similar labeling. Click here for briefing documents concerning the last Advisory Committee meeting. If you have any questions about our comments or NAVIPPRO, please feel free to contact us. Back to top Summary of proposed post-marketing studies Below is a list of the studies King and Purdue presented at the Advisory Committee meeting on October 21-22. Note: At the meeting, King omitted their study to assess the street price differential between prescription opioids that they had previously submitted in their briefing document. Here are slides from the meeting. Purdue Pharma LLP proposed studies: Study 1: Assess changes in methods of preparation, routes of abuse and preferred pharmaceutical opioids in a cohort of abusers of OxyContin©, taken from a population of people abusing OxyContin© who reside in rural Appalachia, a region with one of the highest opioid overdose rates in the U.S. Study 2: Assess changes in routes of abuse of OxyContin© by entrants to substance abuse treatment programs relative to routes of abuse to comparator opioids, based on intake interviews of entrants to substance abuse treatment programs, including adults and adolescents. Study 3: Use internet dialogues to assess changes in the routes of ingestion and preparation methods that people report using to circumvent the new formulation. Data is taken from posts about the new formulation on the internet, including what routes of ingestion and preparation methods that people report using to circumvent the new formulation. Study 4: Assess changes in reported non-medical use of OxyContin©. Study 5: Determine the rates and changes in the frequency of “doctor-shopping” for OxyContin© following introduction of the new formulation. Study 6: Assess changes in rates of overdose associated with OxyContin© among patients and non-patients following introduction of the new formulation. Study 7: Assess changes in the number of exposures and case fatality rate for exposures to OxyContin©, categorized by age. Study 8: Querying 304 law enforcement and regulatory agency officials across 50 states on incidence rates for drug diversion events/cases. King Pharmaceuticals’ proposed studies: Study 1: A cross-sectional study of tampering in opioid substance abusers in treatment, to demonstrate that EMBEDA is associated with a lower proportion of abuse by tampering compared to other oral ER morphine products. Study 2: A cross-sectional prevalence survey among college students for non-medical use of opioids, to estimate the rate of non-medical use by tampering of EMBEDA relative to other oral ER morphine products. Study 3: A cross-sectional study of acute health events from opioid exposures arising from the U.S. population, to demonstrate EMBEDA is abused less by tampering relative to other oral ER morphine products among individuals placing calls to U.S. poison control centers. Study 4: A study of knowledge, attitudes and practices abuse by tampering of EMBEDA among experienced opioid abusers, to determine the differences between EMBEDA and other oral ER morphine products. Back to top About NAVIPPRO The National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) is a public health-oriented risk management solution that integrates the four key components of an effective Risk Evaluation and Mitigation Strategy (REMS): national, real-time, product-specific surveillance; signal detection; signal verification; and empirically validated prevention and intervention programs. NAVIPPRO began in 2001 with a series of grants from the National Institute on Drug Abuse (NIDA). In 2005, Endo Pharmaceuticals became the founding industry sponsor of NAVIPPRO and in 2006 Alpharma Pharmaceuticals LLC. (now King Pharmaceuticals, Inc.) became the second industry founder. Since that time, Shire Development, Inc. has joined in supporting the program, including providing founding sponsorship for the CHAT component. With NIDA’s continued support of ongoing research and product development, NAVIPPRO is constantly evolving to meet our goal of advancing public health. Learn more. Back to top		Analysis of FDA’s Advisory Committee on prescription opioid post-marketing studies Summary of proposed post-marketing studies About NAVIPPRO NAVIPPRO Surveillance Signal detection Signal verification Prevention & intervention DETER Model About Inflexxion Contact Contact us to find out how we can assist you with your risk evaluation and mitigation strategy planning. Subscribe Join the NAVIPPRO Signal mailing list. Support The NAVIPPRO team gratefully acknowledges the support of the NIH, King Pharmaceuticals, Inc., Endo Pharmaceuticals, and Shire Development, Inc.in the development of NAVIPPRO.

	The NAVIPPRO team gratefully acknowledges the support of the NIH, King Pharmaceuticals, Inc., Endo Pharmaceuticals, and Shire Development, Inc. in the development of NAVIPPRO. The contents of this newsletter are for informational purposes only and are not intended to be a substitute for professional medical advice, diagnosis or treatment. Reliance on any information provided in this newsletter is at your own risk. You should consult your physician or other qualified health provider if you have questions about a medical condition. If you think you have a medical emergency, call your doctor or 911 immediately. ©2010 Inflexxion, Inc. All rights reserved.