Division of Pediatric Drug Development
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Division of Pediatric Drug Development Shirley Murphy, MD Director, DPDD March 3, 2003 DPDD DPDD
description
Division of Pediatric Drug Development. Shirley Murphy, MD Director, DPDD March 3, 2003. DPDD. Objectives. Provide an overview of DPDD Update on activities NICHD/FDA Partnership Consultative Activities Across FDA New Labels. What is the Role of Division of Pediatric Drug Development?. - PowerPoint PPT Presentation
Transcript of Division of Pediatric Drug Development
Division of Pediatric Drug Development
Shirley Murphy, MD
Director, DPDD
March 3, 2003
DPDDDPDD
Objectives
• Provide an overview of DPDD
• Update on activities– NICHD/FDA Partnership– Consultative Activities Across FDA– New Labels
What is the Role of Division of Pediatric Drug Development?
• Foster pediatric drug development within FDA
• Partner with NICHD to identify and obtain pediatric information for off-patent drugs
• Provide consultative service to all centers within FDA
What is the Role of Division of Pediatric Drug Development?
• Conduct detailed review of proposed pediatric trials for on-patent drugs
• Contribute to resolution of scientific/ethical issues
• Disseminate new pediatric labeling information
What is the Role of Division of Pediatric Drug Development?
• Partnership with NIH/NICHD
• “FDA-NICHD: Marriage Made In Congress”
NIH/NICHDFDA/DPDD
FDA/NIH Partnership
• Develop “List of Drugs for Which Pediatric Studies are Needed”
– Long, involved iterative process lead by Bill Rodriguez/George Giacoia
– Input obtained from Advisory Committee, FDA Divisions, NIH Divisions, AAP, USP, and Experts.
Development of the List
• The BPCA stipulates that in developing and prioritizing the list, the NIH shall consider;– the availability of information concerning
the safe and effective use of the drug in the pediatric population
– whether additional information is needed– whether new pediatric studies concerning
the drug may produce health benefits in the pediatric population
List Development
5/19/00 FDA publishes list of 426 drugs where further pediatric studies are needed
6/11/02 Pediatric Advisory Subcommittee Meeting
7/02 NIH gives list of 426 drugs to USP
USP removes some on-patent drugs
7/15/02 NIH sends new list of 284 drugs to FDA
FDA reviews list - removes on-patent drugs, biologics, 505b approvals, off-market drugs, duplicates & groups drugs by division/disease
List Development
9/18/02 FDA sends refined list of 180 drugs back to NIH
NIH ranks 180 drugs with input from NIH institutes, AAP and experts
NIH divides drug list
Lower Priority High Priority
(List kept at NIH)
List Development
10/21/02 NIH sends 34 Drug High Priority List back to FDA
FDA review divisions rank drugs on public health benefit, other approved products in
class, other options & adds inpatient/outpatient data
11/27/02 FDA sends 34 Drug List with above information to NIH
NIH obtains written review by subspecialty expert on each drug
List Development
12/10/02 NIH convenes expert panel (AAP, COD, pharmacologists, subspecialty pediatricians, FDA, USP) & each drug is reviewed & scored by
NIH system (100 high-500 low)
Scores totaled by NIH
12/13/02 FDA/NIH meet & select 12 drugs from top 16
1/21/03 NIH publishes “List of Drugs for Which Pediatric Studies are Needed”
2003 List of Drugs for Which Pediatric Studies Are Needed
Azithromycin
Baclofen
Bumetanide
Dobutamine
Dopamine
Furosemide
Heparin
Lithium
Lorazepam
Nitroprusside
Rifampin
Spironolactone
FDA/NIH Off-Patent Drug Process
• BPCA establishes a process to study off-patent drugs in collaboration with NIH
• DPDD performs existing literature/label review
• DPDD writes detailed plan for studies (Written Request)
• No response to WR, NICHD issues Request for Contract (RFC)
Process for the Study of Off-Patent Drugs
Priority List ofOff-Patent Drugs
FDA issues Written Request
Industry agrees to conduct studies
Industry declinesto conduct studies
Referral to NIH
Industry has 30 days to respond
yes
no
FDA/NIH Partnership• RFC for Coordinating Center Published in
Federal Business Opportunities
• RFCs to be published– Nitroprusside - to reduce blood pressure in
pediatric patients– Lorazepam - long-term, continuous sedation
in ICU setting– Lorazepam - treatment of status epilepticus
• 5 other off-patent drugs in process
FDA/NIH Partnership
• NICHD/FDA Newborn Drug Development Initiative
– BPCA recognizes neonates as a specific pediatric subpopulation
– Goal: foster the development of safe and effective drug therapies for the pre-term and neonatal population
FDA/NIH Partnership
• NICHD/FDA to conduct workshop in early 2004 to frame the state of the art and define research priorities for pain control, cardiac, neurological, and pulmonary diseases
• Planning meeting with 50 multidisciplinary experts held 2/10/03
• Working groups established
Consultative Service To All Centers Within FDA
• Devices– Cochlear Implants
– Breast Implants
– GI Devices
– Other
• CFSAN– Infant formula additives
• Other – phthalates
– scientific/safety/ ethical issues
• Formal Consulting Process with Counter-Terrorism
Prussian Blue Label
• Treatment of internal contamination of radioactive and non-radioactive Cesium or Thallium
• Efficacy extrapolated from adult data, safety and efficacy supported by information from pediatric patients exposed in the Goiânia accident
• 27 pediatric patients received PB after exposure to Cesium
• Reduced half life by 46% in adolescents and 43% in children
Labeled Products(6/02 - 2/03)
• Isotretinoin• Famotidine• Omeprazole• Mometasone• Montelukast• Tamoxifen• Lamivudine• Atorvastatin
• Simvastatin• Cetirizine• Pravastatin• Vinorelbine• Atomoxetine• Fluoxetine• Busulfan
Labeled Products with Significant New Information
Montelukast (Singulair) - prophylaxis and chronic treatment of asthma
– dose, PK & AE profile in pts. 12-23 mo. & 2-5yrs.
– new formulations: 4mg chewable tablet & 4mg oral
granule
Labeled Products with Significant New Information
Mometasone (Elocon) - Corticosteroid responsive dermatoses
Cream & Ointment:− evidence of HPA Axis suppression in ped patients 6-23mo.− skin atrophy in pediatric patients 6mo-2yr.− Should not be used for treatment of diaper dermatitis
Lotion:− Safety and effectiveness have not been established in ped patients below 12 yrs and use is not recommended− Should not be used for treatment of diaper dermatitis
Labeled Products with Significant New Information
Tamoxifen (Nolvadex)– safety and effectiveness studied in female patients aged 2-
10 yrs. with McCune-Albright Syndrome and precocious puberty treated for up to 12 months. Long term effects have not been established.
– relative to prestudy baseline
• 50% reduction in frequency of vaginal bleeding
• Reduction in mean rate of increase of bone age
• linear growth rate reduced in majority of patients during treatment
• mean uterine volume increased after 6 months of therapy and doubled at end of 1 yr. study
Labeled Products with Significant New Information
Pravastatin (Pravachol) - Heterozygous Familial Hypercholesterolemia
– new indication in boys and girls 8-18yrs
Atorvastatin (Lipitor) - Heterozygous Familial Hypercholesterolemia
– new indication adolescent boys and girls (post-menarche)
Simvastatin (Zocor) - Heterozygous Familial Hypercholesterolemia
– new indication in adolescent boys and girls (at least one year post menarche) 10-17yrs.
Labeled Products with Significant New Information
Vinorelbine (Navelbine)– no meaningful clinical activity in a variety of tumors
(e.g., recurrent solid malignant tumors, including rhabdomyosarcoma/undiff sarcoma, neuroblastoma, and CNS tumors)
Atomoxetine (Strattera) - ADHD down to 6yrs.
– First non-stimulant (SNRI) drug labeled for ADHD
– NME/non-scheduled drug
– unknown whether final adult height or weight is affected by treatment
– patients on long-term treatment should be monitored
Labeled Products with Significant New Information
Fluoxetine (Prozac) - Major Depressive Disorder (MDD)
Obsessive Compulsive Disorder (OCD)
– Effectiveness established MDD 8-17yrs. & OCD 7-17yrs.
– Decreased weight gain observed with use of fluoxetine as with other SSRIs
• In one 19 week clinical trial ped subjects treated with fluoxetine gained an average of 1.1cm less in height (p=0.04) and 1.1kg less in weight (p=0.008) than those treated with placebo
• height and weight should be monitored periodically in pediatric patients treated with fluoxetine
Labeled Products with Significant New Information
Fluoxetine (Prozac) - MDD & OCD (con’t.)– Mania/hypomania led to discontinuation of 1.8% of
fluoxetine treated patients vs 0% of placebo controlled patients in 3 placebo controlled trials combined
– regular monitoring for the occurrence of mania/hypomania is recommended
Summary
“The FDA is the most interesting and fun place you could ever work”
Jane Henney, MD 5/02
(Former FDA Commissioner)
Please send me the CVs of all your friends
and colleagues.
