Notice Number: NOT-HD-10-008
Key Dates
Release Date: February 17, 2010
Issued by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov)
Purpose
This is a time-sensitive Request for Information that will be used to assess the need to perform pediatric labeling studies of ketamine for short term procedures performed in the Emergency Department.
“This is a Request for Information (RFI). This is NOT a solicitation for proposals, applications, proposal abstracts, or quotations. The purpose of this RFI is to obtain knowledge and information for project planning purposes only.”
Background
The Best Pharmaceuticals for Children Act (BPCA) legislation enacted in 2002 (renewed in 2007), directs the (NIH) in consultation with the Food and Drug Administration (FDA) and experts in pediatric research, to develop and prioritize a list of “off-patent” drugs for which pediatric studies are most urgently needed.
Ketamine has become one of the most favored drugs used by emergency physicians for sedation of children in the Emergency Department. Despite its extensive use, ketamine is not labeled in pediatrics by the Food and Drug Administration. Ketamine has been prioritized for study by NICHD under BPCA since February 2004.
Recently, concerns have arisen about the safety of ketamine due to the appearance of proapoptopic effects in the developing central nervous system in young experimental animals. Neuro-apoptosis have been demonstrated in rodents and non-human primates at doses several fold higher that those used in children. Additionally, in young experimental animals neuro-apoptotic lesions have been associated with long term behavioral deficits.
Information Requested
The NIH is especially interested in concrete and relevant suggestions to the following items in order to determine the scientific and regulatory need to sponsor clinical drug studies on the pediatric use of ketamine for short term procedures in the Emergency Room.
Questions
- Indicate if there are sufficient data to assess the neurotoxicity of single exposure to ketamine. Describe to what extent is the dose(s) used in nonclinical studies relevant to the exposure levels used in ER departments to achieve sedation and analgesia for short-term procedures.
- Indicate if the data on the dosage of ketamine in experimental young animals are applicable to children receiving ketamine for short term procedures in the Emergency Department.
- The vulnerability period for the development of neuroapoptosis lesions after ketamine exposure spans from the third trimester of pregnancy to approximately 3 years of age; however the drug is most commonly used in the ER in children 3 years and older. Indicate if labeling studies could safely be performed in children between 3 and 12 years of age.
- Describe if data on the pharmacodynamics of ketamine in experimental animals are applicable to human study designs. Conversely, describe any issues in experimental studies that need to be considered in the design of pediatric studies.
- Considering the large inter-individual variability in the metabolism of ketamine, indicate if studies should be performed to analyze the effects of polymorphisms (CYP2B6, CYP3A4 and CYP2B6) and ontogeny (CYP2C9) of the ketamine-metabolizing enzymes in pharmacokinetics and adverse events.
- If a two phased study ( i.e., pharmacokinetics and or pharmacokinetics/pharmacodynamics study followed by an efficacy and safety clinical study) is requested, describe which pharmacokinetic and pharmacodynamic measurements and efficacy and safety endpoints should be included.
- Considering that racemic ketamine is used in the United States, indicate if PK studies should include measurements of ketamine enatiometers.
- Describe how the study population of children receiving ketamine for short term procedures in the ER should be defined.
How to Submit a Response
Please provide your response to this Request for Information (RFI) to Lynn Salo at salol@mail.nih.gov no later than March 4, 2010. Responses should be submitted as an e-mail attachment in PDF format. Please limit responses to fifteen (10) pages or less. NICHD will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder’s submission. However, responses to the RFI submitted may be reflected in future solicitation(s). NICHD reserves the right to contact any responder that responds to this RFI for the sole purpose of enhancing NICHDs understanding of your RFI submission. The collected information will be analyzed and may appear in reports.
Disclaimer and Important Notes
This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.
Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities in accordance with the FAR Part 5. However, responses to this notice will not be considered responses to a solicitation.
Confidentiality
No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
Inquiries
Specific scientific questions about this RFI should be provided in writing and directed to the following individual. No questions will be entertained via telephone contact.
Lynn Salo
Contracting Officer
Contracts Management Branch
6100 Executive Blvd., Suite 7A07
Bethesda, Maryland 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Phone: 301-435-6962
Email: salol@mail.nih.gov
Elizabeth Osinski
Contracts Management Branch
6100 Executive Blvd., Suite 7A07
Bethesda, Maryland 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Phone: 301-435-6947
Email: osinskie@mail.nih.gov
and Human Services (HHS)
