NAVIPPRO Signal e-newsletter: FDA to hold public meeting on REMS for certain opioid drugs


	MAY 5, 2009 \| ISSUE 9

	Welcome to the NAVIPPRO Signal. Over the next several weeks, organizations working to improve the risk/benefit balance of prescription pain medications will have important opportunities for sharing research, exploring innovative approaches to reducing risk, and finding new ways to work together. This week, on Thursday through Saturday, the American Pain Society (APS) will hold its 28th Annual Scientific Meeting, which brings together research scientists and health care professionals to discuss the latest findings related to the diagnosis, treatment, and management of acute pain, chronic cancer and non-cancer pain, and recurrent pain. Later this month, on May 27-28, the FDA will hold a public meeting on developing Risk Evaluation and Mitigation Strategies (REMS) for certain opioid medications. The meeting will gather drug sponsors, patient advocacy organizations, and other stakeholders to explore the issues that will determine the final shape of the REMS. (For background, see Issues #5 and #7 of this newsletter.) Below, you’ll find links to the FDA’s announcement of the opioid REMS meeting, a list of some of the questions on which the Agency is seeking public commentary, and additional resources that the Agency has prepared to help educate stakeholders. You’ll also find the abstracts for our posters and presentations at the APS conference, providing details on research we’ve conducted to develop, validate, and refine components of the National Addictions Vigilance Intervention & Prevention Program (NAVIPPRO). We hope you find this issue of NAVIPPRO Signal useful. If you have any questions about NAVIPPRO or our research, please feel free to contact us. Sincerely, The NAVIPPRO team Back to top FDA to hold public meeting on REMS for certain opioid drugs The FDA has announced that it will hold a public meeting on May 27-28 to obtain input on developing Risk Evaluation and Mitigation Strategies (REMS) for certain opioid drugs. The announcement [PDF] describes the possible components of the REMS, and lists specific questions on which the Agency wants input, including: What education should be required of health care providers and pharmacists, so that they are aware of the risks of the products and can counsel patients on the appropriate use of their medication? What education should be provided to patients and should it include a prescriber-patient agreement? How extensive should the REMS restrictions be? Should the REMS include controls on those who distribute the products to pharmacies and other health care providers and, if so, what kinds of controls? What systems already exist that could be used to implement the REMS? What obstacles need to be addressed before the FDA can develop a single, shared system for innovator and generic drug manufacturers? What metrics should the FDA use to assess the success of the REMS? In addition to announcing the meeting, the FDA has prepared additional educational resources. The Center for Drug Evaluation and Research (CDER) and Office of Special Health Issues (OSHI) have created the REMS and Opioid Analgesics Webinar, which is aimed at informing stakeholders about general issues related to REMS and specific issues related to REMS for certain opioid analgesics. Following are details and links to each part of the webinar, as well as links to the accompanying slides. Part I –Introduction (8:21 minutes) Douglas C. Throckmorton, M.D. Deputy Director (CDER) Part II – Opioid Analgesics (6:28 minutes) Sharon Hertz, M.D., Deputy Division Director Division of Anesthesia, Analgesia, and Rheumatology Products (CDER) Part III – REMS (23:51 minutes) John Jenkins, M.D. Director, Office of New Drugs (CDER) Part IV – Next Steps (6:22 minutes) John Jenkins, M.D. Director, Office of New Drugs (CDER) PDF version of slides: Part I - Introduction Part II - Opioid Analgesics Part III - REMS Part IV - Next Steps Back to top Visit us at the American Pain Society (APS) 28^th Annual Scientific Meeting, May 7-9 NAVIPPRO is constantly evolving to meet public health goals. Here’s a look at the abstracts for our posters and presentations at this week’s APS conference, with details on research we’ve conducted to develop, test, and improve elements of the program. If you would like a copy of the posters for any of our presentations, send us an e-mail and we will send you one. Presentations DETER^™: Dynamic Evaluation and Timely Estimates of Rx Opioid Routes of Administration and Abuse Deterrence – S.H. Budman, R. Black, T. Cassidy, J.S. Brownstein, and S.F. Butler. Date: Thursday, May 7, Symposia and Paper Presentations,10:45 a.m.. – 12:15 p.m., Paper Session 307, Poster 143 Prescription opioid abuse remains a significant problem in the U.S. The impetus has been placed on pharmaceutical companies to develop prescription opioid formulations that decrease the likelihood of abuse of these drugs. These abuse deterrent formulations (ADFs) include tamper resistant drugs that resist physical manipulation, drugs that include aversive compounds which may be released if the drug is not taken as it is intended, and prodrugs which are formulated to release the active ingredient only after oral administration and subsequent digestion. DETER: Dynamic Estimates and Timely Estimates of Rx Opioid Routes of Administration and Abuse Deterrence is a model that permits the assessment and post-marketing monitoring of levels of abuse and use of illicit routes of administration (ROAs) for a given ADF. ADAMM^™, the first component of DETER, uses data collected from the ASI-MV Connect database, part of the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) which is a unique, comprehensive, risk management program for prescription opioid and other Schedule II or III therapeutic agents. Using a multilevel, conditional logistic regression model, ADAMM compares the odds ratios of two drug formulations for rates of abuse and route of administration after adjusting for availability of the drug. ROAM^™, the second component of DETER, seeks to empirically establish the relative “attractiveness of abuse” of a ADFs vis-a-vis appropriate comparators. Finally, iPOST^™, the third component of DETER, gathers data from Inflexxion’s Web Informed Services (WIS^™) which uses innovative, scientific methods of Internet data collection to monitor the Internet for efforts to defeat abuse deterrence properties of opioid formulations and to evaluate and track such efforts. Data on the convergent validity of the three components of DETER will be presented based on currently marketed opioid analgesics. DETER shows promise as a method for measuring relative abuse rates and ROAs for ADFs. Estimating attractiveness of not-yet-marketed abuse deterrent opioid analgesics – S.F. Butler, R. Black, J. M. Grimes Serrano, L. Folensbee, A. Chang, and S.H. Budman. Date: Thursday, May 7, Symposia and Paper Presentations,10:45 a.m.. – 12:15 p.m., Paper Session 307, Poster 144 Given the significant increase in non-medical use of prescription opioids in the United States, the impetus has been placed on pharmaceutical companies to develop prescription opioid formulations that may deter abuse. Abuse deterrent formulations (ADFs) that alter the physical and/or chemical properties of the drug to prevent extraction may impact the attractiveness of that drug for those who snort, smoke, or inject prescription opioids. Building upon a previous study, which developed a scale (OATS) to identify the features of an opioid analgesic’s formulation that are relevant to abusers’ decisions about a product’s attractiveness for abuse, we sought to estimate how an abuser of prescription opioids might rate an ADF that is not yet on the market. We developed a method of using substance abuse counselors as proxies for abusers. To address the question of which counselors should be considered as proxies for substance abusers, the counselors’ ratings of the overall attractiveness for abuse of the known products were compared to the average rating obtained from the sample of substance abusers. Of 38 counselor/proxies who rated the drugs, 32 achieved acceptable agreement with ratings made by abusers (average ICC = .84). The counselors/proxies were randomly divided into two groups of 16. Ratings of four known drugs and the not-yet-marketed ADF made by the first group were entered into the model calculations. A cross validation of the derived models was conducted using the second group counselors/proxies. Predicted OATS attractiveness ratings were then calculated. Support was obtained for the hypotheses that the ADF would be classified with (i.e., not significantly different from) a known, unattractive drug and would be significantly different from products that are known to be more attractive for abuse. Finally, as with the original study, attractiveness was found to depend upon one’s preferred route of administration. Posters Implementation of SOAPP^© into a large integrated health care system – K. Zacharoff, A. Bertagnolli, S.F. Butler, and S.H. Budman. Date: Thursday, May 7, Author-attended Poster Session, 4:15 p.m.. – 5:45 p.m., Poster 147 Assessment of risk of misuse or abuse of opioids is rapidly becoming the standard of care for clinicians when the decision is made that opioids are part of the appropriate course of treatment for patients in pain. The Screener and Opioid Assessment for Patients with Pain (SOAPP) has been scientifically validated for use in screening chronic pain patients who are receiving, or under consideration for, long-term opioid therapy. This self-administered questionnaire is convenient for patients to complete and easy for clinicians to score. Along with other components of assessment, clinicians can use the information provided by SOAPP to: (1) better predict a patient's likelihood of misusing or abusing opioids, (2) document the assessment for medical records about clinical decision-making process for use of opioids, and (3) to help identify the appropriate level of monitoring necessary during the course of opioid therapy. While implementation of a screening tool like SOAPP in an individual or small clinical practice can be relatively simple, it can be a much more complex task to incorporate its use into an integrated health care system. This presentation will provide the results of a detailed examination of the necessary steps and strategies involved during a successful implementation of SOAPP by Kaiser Permanente, a large, integrated, national health care system in the United States. Specifically, the presentation will detail the specific steps involved with that implementation, including: (1) planning, (2) educational needs, (3) logistics, (4) documentation, (5) integration into the medical record, (6) workflow integration, and (6) algorithm development for score interpretation and translation into clinical decision making. Additionally, motivation for Kaiser Permanente’s system-wide integration of SOAPP into the assessment process will be addressed, as well as learning points that were discovered as part of the implementation process. painACTION.com: an interactive self-management website for chronic pain patients - E. Chiauzzi, K. Zacharoff, and S.W. Venuti Date: Thursday, May 7, Author-attended Poster Session, 4:15 p.m.. – 5:45 p.m., Poster 117 Pain patients experience a great deal of frustration in daily functioning, despite medical treatment. Patients may benefit from active, self-management interventions that address key medical and psychosocial issues. Cognitive and self-management approaches have proven useful, and can be disseminated widely on the Internet. The Internet offers a vehicle for assisting patients in developing, maintaining, and tracking self-management activities, however, many pain websites are untested, offer few active self-management strategies, or focus on selling products. The aim of this study is to describe the formative research and the development of an interactive website called painACTION.com. painACTION.com is a website for people with chronic back, migraine, and cancer pain and is based on theoretical and clinical approaches that help people cope with chronic pain: (1) self-management skills that enhance daily health practices; (2) collaborative decision-making with a health professional; (3) cognitive behavioral methods to enhance self-efficacy, manage thoughts and mood, set clinical goals, work on problem-solving life situations, and preventing pain relapses; and (4) motivational enhancement through tailored feedback. The content includes articles, interactive skill-based tutorials, self-checks that offer motivational feedback, and user-generated content that is derived from fellow pain patients. The content delivered to users is tailored to the user by a dynamic recommendation engine. As the user engages with the website, the recommendation engine learns about the user and changes recommendations dynamically. Communication with providers is facilitated through a daily pain tracker that prints reports for healthcare providers. painACTION.com is currently undergoing an NIH-funded randomized and controlled back pain field study. This poster will describe the structure and design of painACTION.com and review field trial data, including descriptive data and preliminary outcomes. The development of painACTION.com was funded by small business grants from NIH. Its ongoing maintenance is funded by unrestricted grants from Endo Pharmaceuticals and King Pharmaceuticals. 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 other pharmaceutical companies have become subscribers. 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		FDA to hold public meeting on REMS for certain opiod drugs Visit us at the APS 28^th Annual Scientific Meeting, May 7-9 About NAVIPPRO American Pain Society: 28th Annual Scientific Meeting May 7-9, 2009 San Diego, California REMS for Certain Opioid Drugs: Public Meeting May 27-28, 2009 Washington, DC The College on Problems of Drug Dependence: CPDD 71st Annual Meeting June 20-25, 2009 Reno, Nevada NAVIPPRO Surveillance Signal detection Signal verification Prevention & intervention FDA: REMS for Certain Opioid Drugs: Public Meeting [PDF] FDA: REMS and Opioid Analgesics Webinar painACTION DETER SOAPP 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., and Endo Pharmaceuticals in the development of NAVIPPRO.

	The NAVIPPRO team gratefully acknowledges the support of the NIH, King Pharmaceuticals, Inc., and Endo Pharmaceuticals 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. ©2009 Inflexxion, Inc. All rights reserved.