List of Drugs for Which Pediatric Studies Are Needed

ACTION:

Notice.

SUMMARY:

The National Institutes of Health (NIH) is providing notice of the “Priority List of Drugs for Which Pediatric Studies Are Needed.” The NIH develops the list in consultation with the Food and Drug Administration (FDA) and pediatric experts, as mandated by the Best Pharmaceuticals for Children Act. This list prioritizes certain drugs that are most in need of study for use by children to ensure their safety and efficacy. The NIH will update the list at least annually until the Act expires on October 1, 2007.

DATES:

The list is effective upon publication.

FOR FURTHER INFORMATION CONTACT:

Dr. Perdita Taylor-Zapata, National Institute of Child Health and Human Development (NICHD), 6100 Executive Boulevard, Suite 4A-01, Bethesda, MD 20892-7510, e-mail taylorpe@mail.nih.gov or BestPharmaceuticals@mail.nih.gov, telephone 301-496-9584 (not a toll-free number).

SUPPLEMENTARY INFORMATION:

The NIH is providing notice of the “List of Drugs for Which Pediatric Studies Are Needed,” as authorized under Section 3, Public Law 107-109 (42 U.S.C. 409I). On January 4, 2002, President Bush signed into law the Best Pharmaceuticals for Children Act (BPCA). The BPCA mandates that not later than one year after the date of enactment, the NIH in consultation with the FDA and experts in pediatric research shall develop, prioritize, and publish an annual list of certain approved drugs for which pediatric studies are needed. For inclusion on the list, an approved drug must meet the following criteria: (1) There is an approved application under section 505(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)); (2) there is a submitted application that could be approved under the criteria of section 505(j) of the Federal Food, Drug, and Cosmetic Act; (3) there is no patent protection or market exclusivity protection under the Federal Food, Drug, and Cosmetic Act; or (4) there is a referral for inclusion on the list under section 505A(d)(4)(c); and additional studies are needed to assess the safety and effectiveness of the use of the drug in the pediatric population. The BPCA further stipulates that in developing and prioritizing the list, the NIH shall consider for each drug on the list: (1) The availability of information concerning the safe and effective use of the drug in the pediatric population; (2) whether additional information is needed; (3) whether new pediatric studies concerning the drug may produce health benefits in the pediatric population; and (4) whether reformulation of the drug is necessary. For this year, we are providing an update and a summary of the progress made by the prioritization working group from last year's notice until now, as well as a summary of the annual scientific prioritization meeting held with pediatric experts on December 5-6, 2006.

We have updated the complete list of drugs, listed previously in the April 2006 Federal Register notice, and post it on the BPCA Web site http://bpca.nichd.nih.gov/index.cfm. We will continue to reevaluate this list throughout the year and will provide updates as required, based upon the reauthorization of the BPCA.

In 2005, and with the suggestion of pediatric experts, NIH changed the listing system from a focus on individual off-patent drugs to a therapeutic class-based approach. Pediatric experts indicated that this approach will allow us to compare drugs within a therapeutic class (on and off patent) and give a broader description of the use of these drugs in children. This approach will also allow us to obtain focused expertise in therapeutic areas that will subsequently give us more insight into scientific gaps in treatments of the proposed conditions, as well as feasibility and study designs. Based on expert opinion obtained throughout the year as part of our regular outreach program, a preliminary list of conditions and suggested drugs was drafted and categorized for the 2007 prioritization based on this approach.

The following are the conditions and the drugs discussed in our December 5-6, 2006 scientific meeting with experts in pediatric research: Infectious Diseases, with a focus on Methicillin-resistant Staphylococcus aureus (MRSA) infections; Pediatric Cancer, specifically Neuroblastoma; Neonatal Pain; and Asthma. The gaps in scientific knowledge as well as specific drugs thought to be effective for treatment in each of these conditions were then discussed based on off-patent status, gaps in pediatric labeling, and the potential for providing a health benefit in the general pediatric population. We also provided updates on our current work in the areas of Pediatric Hypertension, Sickle Cell Anemia, and Attention Deficit Hyperactivity Disorder during this meeting. There was also a brief discussion on future areas of consideration, pending the reauthorization of the BPCA, that include topics such as childhood obesity, counter-terrorism research, and Fragile X Syndrome.

Following below are the conditions and drugs we discussed in the December 5-6, 2006, scientific meeting with experts in pediatric research. We will add these conditions and drugs, and their indications for use, to the Priority List for 2007 for which pediatric studies are most urgently needed.

Treatment of Pediatric Cancers: 13-Cis-Retinoic Acid

There is a need for information regarding the pharmacokinetics, safety, and efficacy of 13-Cis-Retinoic Acid in the treatment of neuroblastoma.

Treatment of Pediatric MRSA: Clindamycin, Tetracycline, Doxycycline and Trimethoprim-Sulfamethoxazole

There is a need for further pharmacokinetic and safety data in the use of these drugs to treat children with MRSA infections.

In addition to the above conditions and their associated drugs for consideration, the following are conditions that have been identified as needing improvements in the treatment strategies and/or assessments in pediatrics.

Pediatric Hypertension

Data from the medical literature, clinical trials, and experience were presented and discussed by experts in the field of Pediatric Hypertension. Gaps in knowledge in this field include standardization of blood pressure measurements in children as well as the sequence of drugs for hypertension treatment in children.

Asthma

Data from the medical literature, clinical trials, and experience were presented and discussed by experts in the field of Pediatric Asthma. Gaps in knowledge in this field include gaps in measuring efficacy and safety of treatments and drug delivery systems, especially in young children. There is also a need for the development of new tools to identify symptom measures, pulmonary function tests, biomarkers, and genetics.

Neonatal Research

There are many areas in the field of neonatal medicine that can benefit from advances in neonatal research. Such gaps in research include areas such as determining feasibility of studying specific drugs in low-birth-weight infants based on current use; the development of novel study designs that take into account the small number of patients available due to either ethical limitations and/or feasibility issues; and the performance of clinical studies in areas such as the treatment of pain, neonatal seizures, and bronchopulmonary dysplasia, based on templates that are being developed by experts in research such as the working groups of the Newborn Drug Development Initiative.

For the coming year, NICHD is planning a series of discussions with experts in the fields listed above and plans to identify and work with experts in these respective fields along with our continuing discussions with the other NIH Institutes and Centers. The goal of all of these discussions will be to specifically identify current gaps in scientific knowledge regarding research and treatment of these various pediatric conditions with the ultimate goal of determining future approved drugs for which pediatric studies are needed.