1. Discuss the target population for various opioid formulations and what factors you consider in making this determination?

2. In the context of clinical trials to support an indication for chronic pain, discuss the need to assess sustained efficacy over the duration of the trial.

January 30, 2002: Afternoon Session

1. The FDA is aware that there are still significant unmet needs in pediatric pain management. In the context of the Agency's new mandate to require studies of drugs in children, discuss these unmet pharmacotherapeutic needs in current pediatric pain management and how they might be met with regard to opioid drug products.

2. Discuss the significance of barriers to opioid analgesic trials in children (ethical, safety, scientific, practical, etc). What strategies might be used to overcome barriers?

3. Many different opioid formulations, delivery methods, and drug-device combinations are currently available on the market or may be available in the future (please table in background package). Discuss the age appropriateness and limitations of these various methods of administration, as well as any others that may be useful or particularly hazardous in pediatrics. Are there particular delivery systems that have found a useful niche in pediatric pain management that should be encouraged?
4. It has been historically accepted that the mechanisms of action of opioid analgesics are sufficiently similar between adults and children that large controlled studies demonstrate efficacy, of the nature conducted in adults, have not been required for a pediatric indication. Instead, pediatric trials have been largely focused on investigating safety, pharmacokinetics and appropriate dosing in children. Discuss the shortfalls, if any, to this approach in the ways it has been used to guide and inform the clinical use of opioid analgesics in pediatric patients.
5. Discuss approaches to dose finding and the evaluation of pain in the very young.
6. As new products become available for home use in younger patients, there may be a risk to family members of accidental ingestion, overdose, or deliberate abuse and diversion of these medications. Discuss the strategies for risk communication and risk management that should be considered at the time of pediatric opioid drug approval.

Anesthetic and Life Support Drugs Advisory Committee

January 30 & 31, 2002

Questions to the Committee

January 31, 2002

The Agency is aware of the growing problems of abuse, misuse and diversion prescription drugs, including the opioid analgesics, among patients and non-patients.

1. Discuss the adequacy of the available data to determine the prevalence of addiction among patients treated with opioids for chronic pain. What can we currently say about the prevalence?

2. Discuss how addiction in a chronic pain patient on opioid therapy can be accurately assessed in the office setting.

3. Discuss the pros and cons of excluding patients with a prior history of substance abuse from clinical trials.

4. Discuss the methods of monitoring for addiction in the clinical setting that may be extended to the Clinical Trials setting.

5. In the context of increasing awareness of the problems of diversion and addiction to prescription opioids among patients and non-patients, comment on what measures might be appropriate to consider in the development of an overall risk management strategy that could reduce abuse and diversion without restricting access to drugs by patients in need of treatment. Comment on what components should be incorporated into such programs.