Principal, CNS Drug Consulting LLC
Former Director, Controlled Substance Staff, CDER, FDA*
Senior Advisor, Tufts Health Care Institute Program on Opioid Risk Management

Deborah B. Leiderman, M.D., M.A. provides independent consultation in drug development, drug regulation, and risk management. A Board Certified Neurologist and Fellow, American Academy of Neurology, Dr. Leiderman has extensive public and private sector experience in drug development, regulation, and policy. After 7.5 years at the FDA, Dr. Leiderman is now an independent consultant in drug regulation and policy, and has brought her expertise to Inflexxion as a Senior Consulting Advisor to NAVIPPRO. Her responses in the following interview reflect her personal views and do not reflect past or current FDA official positions or policy.

Q: Tell us about your prior work with the FDA regarding risk management and what you are doing now?

I was recruited from NIDA-NIH in late 1999 and appointed the first Director of the newly formed Controlled Substance Staff within the Center for Drug Evaluation and Research, FDA. Director of CSS/CDER until June 2007, I served as the FDA/DHHS expert on domestic and international drug scheduling, drug control policy, and risk management related to controlled drugs. I led initiatives on prescription drug abuse, surveillance, and risk management.  In my position, I served on multiple Interagency Committees: Drug Control, Narcotic Treatment Policy, Opiate Abuse Working Group, and Synthetic Drug Abuse, to name a few. I collaborated in the development of FDA/CDER Risk Management Guidances and developed Abuse Liability Assessment Draft Guidance.

Currently, I consult to the pharmaceutical industry and to other private and public sector clients including Tufts Health Care Institute, Program on Opioid Analgesic Risk Management. Recently appointed as a Senior Consulting Advisor to NAVIPPRO, I have consulted with Inflexxion on several projects over the past few months.

Q: What is the history of risk management?

Risk management as a paradigm and as a set of programs and tools for drug products was created to supplement the standard drug label, or package insert, for drug products viewed as having special risks. It is important to remember that all drug products, devices, and interventions carry risk--after all, life is full of risks. The risks of a particular drug have to do with unknowns and uncertainties about the drug product as well as with individual patient variability. For most drug products, the drug label, or package insert, is the primary method for communicating vital information. In a nutshell, the tools and programs of risk management provide additional mechanisms and efforts to help ensure proper use and to reduce adverse outcomes and safety problems. For opiate analgesics, the goals of risk management programs are to support appropriate prescriber, patient, and caregiver education and ultimately to reduce drug abuse, misuse, overdose, and associated morbidity and mortality.

Q:  Is risk management evolving? If so, how?

There is no question that risk management is a dynamic area.Public health, industry, and regulatory approaches to risk management are evolving. Currently, most new drug products that are approved don't require special risk management tools, but as you know, drug safety has been under scrutiny by Congress and has been the subject of new legislation.Active efforts by members of Congress and patient advocates have focused on more regulation of post-marketing safety, including more systematic surveillance for and reporting of safety signals post-approval.

Q: How should risk management be responsibly integrated by pharmaceutical companies?

As I see it, risk management should be integrated throughout the entire product development lifecycle. Risk management is a multistep process: collecting data, analyzing it, and then responding appropriately. Surveillance is a critical component of risk management; however data collection alone is not risk management. Manage is a verb--implying action! Risk management by pharmaceutical companies needs to incorporate a range of activities, including prevention, surveillance, intervention, and effective educational tools. A critical component of the FDA RiskMAPGuidances specifies assessing the effectiveness of RiskMAP actions and tools. There needs to be accountability--evidence that the RiskMAP works or that new approaches will be developed and assessed. So the challenge for pharmaceutical companies is that they may be developing, assessing, and refining their risk management tools in parallel with developing and marketing new drug products.  

Q: For pharmaceutical companies that market opioids, is there a responsibility to address the public health issue of addiction?  

Yes, they have a clear role and a range of responsibilities starting with the development of the drug product. Using responsible promotional and educational activities, manufacturers of drugs play an important role in ensuring that their products are being prescribed appropriately to the appropriate patients. Prevention of problems is always the best approach to public health concerns. I can't emphasize prevention enough. Once there is an established abuse and addiction problem in the community, you not only have significant morbidity and mortality, there is ongoing demand, drug seeking, and all the attendant social and criminal problems.

Q: What role does risk management have for pharmaceutical companies beyond prevention?

Pharmaceutical companies can use risk management to characterize the prescribing and medical/non-medical use of their products. If high risk patients are identified, the choice of drug product may be modified: special monitoring, more frequent reassessments, and other tools may be introduced. Opioids are controlled substances because of their intrinsic rewarding and reinforcing properties--the risk and problem of abuse cannot be completely eradicated. However, it is critical to emphasize that opioid analgesics are indispensable for treating pain. Managing the risks associated with abuse and misuse is essential to ensuring that these drugs remain available to patients that need them. To the extent that the serious problem of opioid analgesic abuse, misuse, overdose, and addiction remains uncontrolled, there are potentially serious consequences for patients in need and well-intentioned health care professionals.

Dr. Leiderman received her M.D. and M.A. degrees from the University of Pennsylvania and trained in Neurology at Stanford University Medical Center.  She has published extensively in neurology and clinical trials, and has presented widely before national and international audiences. Dr. Leiderman can be contacted at dleiderman@cnsdrugconsult.com.

* The views expressed in this interview are Dr. Leiderman's and do not reflect past or present official FDA policy.

Understanding the ways that prescription drug abusers gain access to prescription opioids is an important element in the risk management of these medications. Presented in June 2007 at the College on Problems of Drug Dependence (CPDD), NAVIPPRO data were used to examine different sources of prescription opioids as a function of patient age, gender, and race. These data were obtained through Inflexxion's ASI-MV® Connect database, a continually growing collection of over 18,000 self-reported, opioid related interviews used to assess patients admitted to substance abuse treatment. The computer-administered interviews are uploaded daily to the ASI-MV Connect database, keeping information accurate and up-to-date.

In an earlier sample of 6,163 interviews, 32% of assessed patients indicated abuse of at least one prescription opioid in the past 30 days. Analyses of prescription opioid abusers found common demographic patterns for their source of opioid analgesics. For this study, four specific products; Vicodin®, OxyContin®, Kadian®, and Avinza® were examined. Mostly, these drugs followed the basic patterns for gender, age, and race; however, some interesting product-specific differences were noted.

Across all prescription opioids, women are more likely to obtain abused opioids from their own prescription. Similarly across all prescriptions, men are more likely to purchase prescription opioids from someone they identified as a drug dealer. Individuals older than 45 were more likely to get prescription opioids from their doctors and less likely to get the drugs from a family member or drug dealer. Although numbers were small, there was a significant trend for individuals 35 or younger to report stealing their prescription opioids. Caucasian prescription opioid abusers were more likely than minority abusers to obtain these drugs from a family member or a drug dealer.

Vicodin® - a difference between men and women using their own prescription to obtain their drugs was only evident for Vicodin abusers. Also, a significantly greater proportion of Vicodin® abusers obtained their drug via their own prescription. Conversely, Vicodin abusers were significantly less likely to obtain their drug via a dealer.  Finally, individuals older than 35 were more likely to use multiple doctors to obtain Vicodin for abuse. 

OxyContin®- women OxyContin abusers were significantly more likely to access this drug via family members. In addition, only OxyContin showed a significant difference between age groups and stealing as a drug source: 18% of OxyContin abusers younger than 35 admitted to stealing OxyContin.  

Kadian® and Avinza®- Kadian and Avinza abusers tended to show very similar patterns of source for these drugs. Neither Kadian nor Avinza showed any of the gender differences found for other prescription opioids; however as with the other drugs, individuals older than 35 were more likely to obtain these drugs from their own prescription. Other age differences were not found for Kadian.  For Avinza, individuals between 36 and 45 years old were more likely to use multiple doctors and individuals older than 45 were significantly less likely to obtain Avinza via a dealer. 

To learn more about findings from this and other NAVIPPRO research, please e-mail NAVIPPROnewsletter@inflexxion.com.

NAVIPPRO Signal interviews Dr. John S. Brownstein, Instructor of Pediatrics at Harvard Medical School and a Senior Consulting Advisor to NAVIPPRO.

Dr. Brownstein answers questions on the role of biosurveillance in opioid risk management and what lessons can be learned from other areas of population health monitoring.

Submit your questions for Dr. John Brownstein now and be sure to read his answers in the upcoming interview!