NAVIPPRO Signal e-newsletter: Developing science-based metrics and educational initiatives for REMS


	JUNE 15, 2009 \| ISSUE 10

	Welcome to the NAVIPPRO Signal. On May 27-28, the FDA held a public meeting to hear from diverse constituencies on the issues that will shape the development of Risk Evaluation and Mitigation Strategies (REMS) for certain extended-release and long-acting opioid medications. Among the key questions: What is the optimal way to mitigate the risks associated with these medications, such as aberrant drug-related behaviors that often have lethal consequences? How important is education to mitigating these risks? And once a REMS program has been implemented, how do we scientifically measure its impact over time? Members of the National Addictions Vigilance Intervention & Prevention Program (NAVIPPRO) team gave presentations at the meeting to address these questions. Below, you’ll find brief synopses of these presentations, plus links to the accompanying slides. You’ll also find our abstracts for the forthcoming College on Problems of Drug Dependence (CPDD) 71^st Annual Meeting (June 20-25), which provide details on research we’ve conducted in these areas. This includes research comparing data collected through NAVIPPRO with data collected through the National Survey on Drug Use and Health (NSDUH), the American Association of Poison Control Centers (AAPCC), and the Drug Abuse Warning Network (DAWN Live!). 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 Developing science-based metrics and educational initiatives for REMS The FDA held a public meeting on May 27-28th to discuss proposed elements for Risk Evaluation and Mitigation Strategies (REMS) for certain extended-release opioid medications. Following are brief descriptions of presentations by members of the NAVIPPRO team: Is the REMS Working? Using Data from Adult and Adolescent Substance Abuse Centers, Simon H. Budman, Ph.D., Founder, President & CEO, Inflexxion [Slides] Dr. Budman began by stressing the need for science-based metrics to evaluate the efficacy of an opioid REMS. He pointed out that the detection and verification of signals of aberrant drug-related behaviors will be a key indicator of whether a REMS program is reducing risk. Dr. Budman then introduced the surveillance components of NAVIPPRO as a tool for measuring risk mitigation over time. These components have been developed and tested over the past decade with $15 million in support from the National Institutes of Health (NIH) and industry sponsors. Through these components, NAVIPPRO delivers a unique real time data stream from substance abuse treatment centers across the country. Dr. Budman proceeded to explain that this data stream is comprised of two sources: patient assessment data from adults in treatment, collected through the Addiction Severity Index- Multimedia Version, or ASI-MV^© Connect, and assessment data from adolescent patients in treatment, collected through the Comprehensive Health Assessment for Teens, or CHAT^™. When a patient completes either the ASI-MV or CHAT interview at a treatment center using the ASI-MV Connect system, de-identified, aggregate data are uploaded to Inflexxion’s secure database for review and analysis. The interview collects data about the abuse of specific drug products, including where a patient obtained the product and the route of administration used. These data can be used to provide a temporal and geographic picture of abuse, identifying where, when, and how a particular product is being abused among a sentinel population. NAVIPPRO’s data streams, Dr. Budman asserted, can be valuable for evaluating the efficacy of a REMS for a number of key reasons. First and foremost, the ASI-MV Connect system is REMS-ready: it is an existing data source that has already been validated and can readily be incorporated into the REMS. Second, the data stream is unique: ASI-MV Connect is the only system that systematically collects real-time, product-specific data from nearly 500 substance abuse treatment facilities across the country (with additional sites being added at a rate of 20 per month). Third, because ASI-MV Connect provides product-specific information, it allows for adjustments of the REMS based on the specific abuse patterns of an individual medication. Fourth, the ASI-MV Connect system is rapidly becoming more comprehensive: it contains data from patients located in 76% of the country’s three-digit zip code areas, including the entire state of New Mexico, and other states are currently considering adopting the system state-wide. Finally, with the addition of CHAT, the system has the potential to provide unprecedented access to information about adolescents’ abuse of prescription drugs. Dr. Budman concluded by noting that NAVIPPRO may be especially well suited to support an opioid REMS program, since it would: Provide the opportunity to leverage four years’ worth of geospatial data and trends, with approximately 100,000 cases in the database Offer the ability to observe and research the impact of a REMS, and enable corrections and modification to the REMS as needed Provide an ideal location for a pilot REMS: New Mexico, which has adopted ASI-MV Connect for all of its substance abuse treatment centers Pain Education Initiatives for Providers, Patients, and Vulnerable Populations, Kevin L. Zacharoff, M.D., Director of Medical Affairs, Inflexxion [Slides] A clinician with more than 25 years of experience treating patients in pain, Dr. Zacharoff spoke at the REMS meeting as an educator. He underscored the importance of meaningful education in a REMS program, and advocated specifically for targeting primary care clinicians, whom he noted might be less comfortable prescribing opioid medications, as well as fearful of the perceived barriers associated with this class of medications. Dr. Zacharoff also identified patients, and specific vulnerable patient populations such as college students, as among those who need to be educated about the safe and effective use of opioid medications, and the dangers of engaging in aberrant behavior. Dr. Zacharoff emphasized that terminology is one of the building blocks of cultural change, a process that should begin with educating clinicians about aberrant drug behavior, and how to distinguish among abuse, misuse, tolerance, and dependence. He noted that of the 375, 000 clinicians who prescribe extended-release and long-acting opioid medications, only 5,000 are pain experts, with the knowledge base necessary to navigate along the continuum of pain treatment for patients with chronic pain. Many initiatives at Inflexxion, Dr. Zacharoff continued, focus on minimizing the risks associated with treating pain using extended-release opioids. Clinicians think about things differently than other stakeholders, he said, and they respond better to initiatives that address information in terms they understand. The goal in designing an education component for the REMS should be to pair basic information about these drugs with clinical guidance on how to prescribe them safely and appropriately when indicated. Dr. Zacharoff then described PainEDU.org, one of the key educational intervention and prevention components of NAVIPPRO. The mission of PainEDU is to provide unbiased, non-promotional, clinically meaningful information. He noted that it seemed as if PainEDU had stumbled into a “vacuum,” drawing the attention of non-expert clinicians who were already seeking knowledge in this important area. This has been evidenced in the growing number of registrants at the PainEDU website, which now surpasses 20,000 users, as well as the tens of thousands of people who access components of the site without registering. Through its continuing evolution, said Dr. Zacharoff, PainEDU has been able to facilitate the generation of information in a bidirectional and unbiased way. “We reach a lot of people,” he said, “and they reach back out to us to tell us what they want to learn more about.” Dr. Zacharoff concluded by outlining a case study on the integration of one of NAVIPPRO’s risk management tools, the Screener and Opioid Assessment for Patients with Pain (SOAPP^©), currently available on the PainEDU site, into the Kaiser Permanente Health System. Integrating the tool in the system required a multi-faceted implementation plan, noted Dr. Zacharoff, including a critical component: additional training for primary care clinicians. Back to top Visit us at the CPDD 71^st Annual Meeting – June 20-25 The College on Problems of Drug Dependence (CPDD) 71^st Annual Meeting kicks off this coming Saturday, June 20^th, in Reno, Nevada. Here is a preview of the presentations that we'll be giving on research we have conducted to validate, refine, and improve components of NAVIPPRO. Please note that the data in these abstracts represent information that was accurate at the time the abstracts were submitted. For updated information, please contact us. Finally, if you would like a copy of any of our posters, send us an email. We will be happy to send you one. Geographic and contextual factors of prescription opioid abuse: Results from ASI-MV Connect – Green, T.C., Brownstein, J.S. & Butler, S.F. Details: Oral Communications 3: “Prediction of Addiction,” Monday, June 22, 8:45 a.m. Aims: Drug abuse exhibits clear geographic patterns, often associated with underlying population demographics. We aimed to determine correlations between empirical patterns of abuse and key geographic and contextual factors: drug availability, arrests for sale and possession of synthetic and nonsynthetic opioids, and residence in rural/urban areas. Methods: We built on results of a latent class analysis (LCA) derived from ASI-MV Connect, a national database of self-reported drug abuse behaviors from patients admitted to substance abuse treatment, aggregated at the 3-digit zip code (141 zip codes from 31 states). We matched the 6-class LCA data to variables from 2007-2008 Verispan prescription sales data, 2005 US Department of Justice Uniform Crime Reports, and 2000 US Census Rural Urban Commuting Areas. Spearman or Pearson correlations and Kruskal-Wallis or ANOVA tests were conducted, as appropriate. Results: The OxyContin+heroin class membership was associated with greater availability of oxycodone, more arrests for possession and sale/manufacture of synthetic opioids as well as sale/manufacture of opiates/cocaine, and they were least likely to reside in rural and small town zip codes. Higher probabilities of class membership in the methadone class and the healthy abusers class occurred in zip codes with increased availability of morphine and oxycodone. Poly-prescription opioid injector class membership was correlated with zip codes exhibiting greater availability of hydrocodone, morphine, and oxycodone. The poly-prescription opioid abusers who snort class was associated with more arrests for possession of synthetic opioids and was least likely to reside in Micropolitan zipcodes. Rural areas tended to have zip codes with predominant prescription opioid injector and snorter classes. Prescribed misusers class membership was associated with small town zip codes. Conclusion: Important geographic and contextual associations with distinct profiles of prescription opioid abusers exist. Interventions aimed at structural level factors may hold promise for reducing abuse of prescription opioids in some areas. Sources of Support: Work supported by a NRSA grant (TCG) from the National Institute on Drug Abuse (NIDA). Abuse Deterrent Adjusted Measurement Model: ADAMM^™ – Black, R.A., Budman, S.H., Cassidy, T.A. & Butler, S.F. Details: Oral Communications 3: “Prediction of Addiction,” Monday, June 22, 9:15 a.m. The abuse of prescription opioid medications has placed an impetus on pharmaceutical companies to develop so-called abuse deterrent formulations (ADFs) for opioid medications. It is critical to establish methods to determine the impact of such formulations on actual abuse rates. ADAMM is proposed as an approach for assessing the odds of abuse for an ADF in relation to appropriate comparators. Aim: To provide an initial test of ADAMM by examining the odds of abusing an existing drug, OxyContin^©, in relation to: (1) Duragesic^©, (2) MS Contin^©, and (3) Vicodin^© using NAVIPPRO data from patients seeking substance abuse treatment across the U.S. Methods: Data from 3,516 patients in substance abuse treatment representing 47 3-digit home zip codes, were analyzed. A multilevel logistic regression analysis estimated the odds ratio of abusing OxyContin^© vis-�-vis the comparator medications. Results: Results revealed the odds of abusing OxyContin^© was 9.77 times the odds of abusing Duragesic^© (95% CI: 6.71, 14.23), 1.15 times the odds of abusing MS Contin^© (95% CI: 0.45, 1.57), and 0.33 times the odds of abusing Vicodin^© (95% CI: 0.26, 0.41), after adjusting for local, prescribed availability. Local availability was defined as the total number of morphine equivalent grams dispensed by pharmacies during the current and previous two months divided by the population density in each 3-digit patient home zip code area. Conclusion: These results illustrate a model that appears to be capable of determining the odds of abusing one prescription opioid compared to another after adjusting for local availability of the product. As ADFs enter the market, this model will permit direct comparison of an ADF with appropriate comparators adjusted for local, dispensed availability. Since "abuse deterrence" may be a dynamic characteristic (e.g., it may change over time), ongoing monitoring of an ADF's odds of abuse with respect to comparators will be essential. This model shows promise as way of evaluating an ADFs public health impact. Sources of Support: This study was supported by Inflexxion, Inc. Relative rates of prescription opioid abuse: Comparison of public health databases – Butler, S.F. & Brownstein, J.S. Details: Oral Communications 7: “A Royal Flush of Prescription Opioid Epidemiology,” Monday, June 22, 10:00 a.m. Objective: Interest in the post-marketing surveillance of prescription opioids continues to grow. While these efforts generally use multiple data streams, how these data are related to each other is not well understood. This study examines three, real-time, product-specific datasets that are part of National Addictions Vigilance Intervention & Prevention Program (NAVIPPRO): the ASI-MV Connect (patient-level data from 360 addiction treatment facilities) and two Web-Informed Services —Geotemporal Real-time Internet-based Intelligence for Drugs (Media-GRIID^™; surveillance of over 20,000 news outlets), and Internet Monitoring of web chatter on prescription drugs. We examined relative rates of abuse estimated by these three datasets and compared ASI-MV Connect data with data from NSDUH, American Association of Poison Control Centers (AAPCC) and DAWNLive! The TEDS dataset was excluded as it provides no opioid-specific information. Number of Subjects: ASI-MV Connect contains 55,341 cases, WIS^™ contains 2,051,976 online posts, and in Media-GRIID, 45,185 articles mention prescription opioids. Procedures: Rates of prescription opioid products and compounds were calculated in each database for overlapping timeframes (July 2007 to October 2008). Spearman rho correlations compared relative rankings of products/compounds. Results: Significant correlations were found between the ASI-MV Connect data and Internet monitoring mentions (.70) and with media mentions (.67), with Internet monitoring and media correlating .71. Further analyses compared relative rates of these datasets with three publically available datasets, again with high levels of correspondence. ASI-MV Connect data correlated with AAPCC data at .72, .81 with DAWNLive! mentions ("other" category), and .90 with NSDUH data. Conclusions: This the first study to compare the relative rates of prescription opioids represented in surveillance datasets. Future research will consider time series analyses to examine correspondences across time to further understand which data are leading and which are following indicators. Sources of Support: Inflexxion, Inc. Validation of CHAT: An interactive, multimedia scale to assess alcohol and substance addiction severity among adolescents – Trudeau, K.J., Lord, S., Black, R., Lorin, L., Cooney, B., Villapiano, A. & Butler, S.F. Details: Poster Session IV: “Diagnosis and Assessment,” Thursday, June 25, 8:00 a.m. – 9:00 a.m. Aim: To construct a valid and reliable interactive, multimedia, self-report scale on alcohol and substance addiction severity among adolescents for use in treatment settings. Methods: A total of 356 adolescents (ages 13 – 18) participated in this study. The normative sample included 94 adolescents from two high schools in Massachusetts. The treatment sample included two groups: Test-retest was conducted with 49 adolescents. Comparison measures and the scale were completed by another 213 adolescents. Results: Results from a confirmatory factor analysis (using maximum likelihood estimation) revealed a valid model measuring addiction severity, (39) = 61.57, p=.01, CFI = .99, RMSEA = .04. The model consists of six domains: (1) Family Relations, (2) Peer Relations, (3) Psychological Issues, (4) Tobacco Use, (5) Alcohol Use, and (6) Substance Use. Each domain has two manifest variables, one variable measuring severity (e.g., number of psychological symptoms) and the other variable measuring frequency of problem (e.g., number of days in the past 30 days had psychological problems). All manifest variables measure current or recent (past 30 days) level of functioning. Domain level test-retest reliability ranged from r = 0.62 to as high as r = 0.91. Convergent/Discriminant validity was measured by examining bivariate correlations between each domain and comparison measures. As expected, comparison measures were more highly correlated with the target domain as compared to other domains. Domain level composite scoring was derived from the normative sample of 94 participants from local high schools. Conclusion: The Comprehensive Health Assessment for Teens (CHAT) has acceptable validity and reliability for use in the treatment setting. Sources of Support: This study was supported by an SBIR grant awarded to Inflexxion (NIDA: 5R44D A014139-04, PI: Sarah Lord). 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		Developing science-based metrics and educational initiatives for REMS Visit us at the CPDD 71^st Annual Meeting – June 20-25 About NAVIPPRO 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 Agenda for May 27-28 2009 Opioid REMS Public Meeting [PDF] 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.