Thank you for the opportunity to speak today. My name is Dr. Megan Polanin. I am a Senior Fellow at the National Center for Health Research, and I previously trained at Johns Hopkins University School of Medicine. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from industry, so I have no conflicts of interest.
Our Center strongly supports the purpose of the pediatric assessments under the Pediatric Research Equity Act (PREA) to obtain data that will support the safe and effective use of new drugs in pediatric patients who already use or may benefit from their use. We also support the purpose of this FDA meeting to discuss potential additions to the labeling of an opioid analgesic, Butrans, intended for use in children ages 7 to 16.
It is important to address the medical needs of children as effectively and safely as possible. Most opioid analegesic products have not been studied in pediatric populations, and there is a lack of pediatric use information in drug product labeling. It is critical to provide clinicians with age-appropriate information regarding the safety and pharmacokinetics of opioid analgesics. This is only possible when we have evidence from high-quality clinical trials in children.
We are concerned that Study 3031 is too small, too short, and includes some patients who are not appropriate to be included. Despite what the company described as extensive recruitment efforts, the current required post-market study included only 41 patients, 35 of whom were ages 12-16, and only 6 patients were ages 7-11. Although the total sample size meets the initial requirement for this study, the recommended size of the sample has subsequently increased from 40 to 125 patients for the 12-17 age group and 50 patients for the 7-11 age group.
FDA’s advice for this study was that 40 completers have at least 6 months of exposure in order to assess safety. However, only 12 patients were exposed to Butrans for 24 weeks or longer – all of whom were in the 12-16-year age group.
In addition, patients in this trial had 19 different primary conditions that various investigators judged to meet the eligibility criteria for the study. FDA reviewers noted that some of these conditions do not generally reflect the currently accepted indications for the use of ERLA opioids for children and adolescents.
Our questions are: Why include information about a study that is flawed and does not meet current standards? Will the proposed labeling be helpful for providers and patients in real-world clinical settings? Will it be misleading? We are concerned that including the information will tend to encourage physicians to prescribe the drug to children.
The small sample size and duration of treatment for most children are not adequate to provide evidence that this drug is safe for children. For example, five patients discontinued trial participation due to ECG-related adverse events, and Butrans could not be ruled out as a contributor for 3 of these patients. Serious adverse events also led to study discontinuation for three other patients. Twenty percent of patients experienced treatment-emergent serious adverse events that were more common in the 7-11-year age group, though researchers concluded that events were not caused by the drug.
It is important for this panel and the FDA to make decisions about drug labeling based on sound science and strong data. We concur with the 2016 Advisory Committee that because pediatric patients are vulnerable to drug use and addiction due to ongoing brain development; proper prescribing, patient selection, and education are crucial to optimize safety in this population. Results of Study 3031 do not provide sufficient evidence to inform health care providers about the safe use and proper dosing of Butrans in the management of pain for pediatric patients.
We urge this Advisory Committee to advocate for pediatric patient safety and encourage the FDA to require that the drug be adequately evaluated before allowing information about Butrans to the pediatric section of the labeling.
Thank you for the opportunity to share our perspective.
The Pediatric Advisory Committee discussed concerns regarding the data from the evaluation of Butrans in pediatric patients and whether information from Study 3031 should be included in the Butrans label. No voting questions were presented to the Committee.