January/February 2010 |  ISSUE 15

  
 
 

Welcome to the NAVIPPRO Signal.

In January, a new study published in the Annals of Internal Medicine concluded that among patients legitimately prescribed opioids, those who are prescribed higher doses are at increased risk of overdose.1 According to an editorial co–authored by ONDCP Deputy Director A. Thomas McLellan, Ph.D., these findings demonstrate the need to change the way physicians prescribe opioid medications.2

“The threat to patient safety is too great to allow current pain management and opioid–prescribing practices to remain as they are,” he writes. “Dunn and colleagues′ data show the need to assess the risk for opioid misuse, provide close oversight, dose judiciously, and continually reevaluate the benefit of these potentially risky drugs.”

Below, you′ll find an article exploring the potential impact of the findings in the medical community, as well as the implications for opioid risk management as we move closer to what′s expected to be a class–wide Risk Evaluation and Mitigation Strategies (REMS) for certain extended–release opioid medications.

In addition, we provide pointers to information on the December 4, 2009 public meeting of the FDA and the Industry Working Group (IWG) on the development of the opioid REMS, as well as Inflexxion′s docket submission in the proceedings.

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

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Navigating the shift to REMS: A clinician′s perspective

By Kevin L. Zacharoff, M.D.

The study by Dunn and colleagues referenced above has been published at a time when there is already quite a bit of controversy regarding the management of chronic non–cancer pain with long–term opioid therapy.3 Among the issues that have been raised are concerns about efficacy, overall benefit, and hyperalgesia. However, much of the “storm” of debate has and will continue to surround the issue of patient safety and protection from unintended consequences, such as overdose.

There are numerous tools and approaches for managing the risks of opioids, but outside of the specialist setting, uptake of these approaches has been slow. There are many possible reasons for the slow pace, including deficits in education, lack of consultative support, and concerns about the impact on clinical workflow.

The new findings may stir further debate and introduce additional challenges. Dosing ceilings have typically been met with a fair amount of resistance. Clinicians must understand and respond to tolerance and dependence. Those who have experience with treating chronic–pain patients will attest to the fact that when it comes to dosing, different patients have different plateaus and ceilings. And there has been a strong push in the medical community not to under–treat patients with chronic pain.

In short, in the absence of data showing that higher doses of opioids increase risk, there has been an approach to dosing led by the clinical goals of improving patients′ quality of life and absolute pain scores. If it is confirmed that risk is related to dosing, the question will then become whether a high dose for one patient is a high dose for another — and how can risk be stratified or controlled, given the absence of an absolute limit.

What does this mean for opioid risk management, particularly as we move toward class–wide, federally required REMS for opioids?

We at Inflexxion launched the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) to enable a systematic, scientific approach to pharmaceutical risk management, incorporating the use of evidence–based tools for risk stratification. As Director of Medical Affairs, I work with health care organizations to integrate these tools in their risk management plans — and despite the many challenges articulated above, in the past three years I have seen interest explode.

From my perspective, then, there is no question that health care organizations and clinical practices are already moving in the “right” direction. And as more clinicians are exposed to and learn about the importance of opioid risk assessment, both for clinical and documentation purposes, the “value proposition” will become intuitive.

But how do we get from here to there? The debate and discussion surrounding opioid REMS may help spur organizations to examine their opioid risk management procedures and ensure that they adhere to recommended best practices.

Fortunately, last year, the American Pain Society (APS) and the American Academy of Pain Management (AAPM) released a groundbreaking set of evidence–based guidelines to assist clinicians in using opioid medications to treat patients for chronic, non–cancer pain. The guidelines recommend the use of screening tools to assess risk before initiating opioid therapy, including the Screener and Opioid Assessment for Patients with Pain (SOAPP).4

Today, there is new evidence supporting the utility of these tools. A group of researchers, including leading pain specialist Steven D. Passik, Ph.D., conducted a study to compare the sensitivity of a semi–structured clinical interview and three screening tools: the SOAPP, the Diagnosis, Intractability, Risk, and Efficacy inventory (DIRE), and the Opioid Risk Tool (ORT).

Results showed the highest sensitivity for the clinical interview (0.77) and the SOAPP (0.72), followed by the ORT (0.45) and the DIRE (0.17). In addition, the researchers found that combining the clinical interview with the SOAPP increased sensitivity to 0.90.5

The authors note that the study has the potential to help pain centers and specialists by providing “valuable information about risk measurement to utilize their resources efficiently, increase their ability to detect risk, and add safeguards to reduce risk when indicated.”

Regardless of the outcome of the opioid REMS development process, findings like these point the way to the future of pain management, one in which clinicians will have ready access to tools that can help them deliver care with the highest level of safety and vigilance. This is good news for health care organizations, clinicians, and patients.

At Inflexxion, our focus is on risk management that incorporates accurate, real–time data about the use of opioid and stimulant medications. We are also deeply engaged with the pain and addiction treatment communities. If you would like to talk to us about NAVIPPRO and our experience in helping organizations develop evidence–based risk management plans, please feel free to contact me.

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FDA meets with IWG to discuss opioid REMS

On December 4, 2009, the FDA held a public meeting with the Industry Working Group (IWG) representing the makers of certain extended–release opioid drug products. The purpose of the meeting was for the drug makers to share information with the FDA on the status of the IWG′s proposals for opioid REMS.

Following are links to FDA′s archived materials:

For detailed coverage of the meeting, see Safety Plan for Opioids Meets Resistance: Opioid–Linked Deaths Continue to Soar, published this month in the Journal of the American Medical Association (Volume 303, Issue 6: 495-497).

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Inflexxion submits comments on NAVIPPRO surveillance to opioid REMS docket

Responding to the FDA′s call for comments [PDF] on the development of a class–wide REMS for certain extended–release opioid medications, Inflexxion has submitted a comment that examines how REMS can be evaluated, providing details on how the surveillance component of NAVIPPRO can provide timely and highly specific data in the following areas:

  • Product(s) being misused/abused (what is being abused?)
  • Routes of administration (how is it being abused?)
  • Geospatial localization (where it is being abused?)
  • Diversion (how is it being diverted?)
  • Abuser characteristics (who is involved in abusing? And the differential impact on adolescents and patients with pain)

Following is a link to the docket submission:

Evaluation of Risk Evaluation and Mitigation Strategy (REMS): Comments for Docket No.FDAᰫ2009–N–0143 [PDF]

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References

1Dunn, K., Sauders, K., Rutter, C., Banta–Green, C., Merill, J., Sullivan, M., et al. (2010). Opioid prescriptions for chronic pain and overdose: a cohort study. Annals of Internal Medicine, 152(2):85-92.

2McLellan, A.T. & Turner, B.J. (2010). Chronic noncancer pain management and opioid overdose: Time to change prescribing practices. Annals of Internal Medicine, 152(2):123-124.

3Collins, T. (2010, February 17). Opioids for noncancer pain a subject of hot debate: An expert interview with pain specialist Ajay Wasan, M.D., M.Sc. Medscape Medical News. Retrieved from http://www.medscape.com/viewarticle/717147

4Chou, R., Fanciullo, G., Fine, P., Adler, J., Ballantyne, J., Davies, P., et al. (2009). Clinical gidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain, 10(2):113-230. doi:10.1016/j.jpain.2008.10.008

5Moore, T., Jones, T., Browder, J., Daffron, S., & Passik, S. (2009). A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Medicine, 10(8):1426-1433. doi:10.1111/j.1526-4637.2009.00743.x

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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.

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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.