Pediatric Safety Surveillance Workshop

Transcription

1 Pediatric Safety Surveillance Workshop Pediatric Safety: Better Surveillance for Children Dianne Murphy, MD, FAAP Office of Pediatric Therapeutics Office of the Commissioner, FDA September th,

2 N=1 Is Not Good Public Policy Children deserve the same level of evidence that is required for adults to determine that therapies used by children are safe, effective and properly dosed. Children are a heterogeneous group who undergo rapid metabolic, hormonal, physiologic and developmental change. Over the last two decades, FDA has actively supported many efforts to encourage development of information on appropriate use of therapies in the pediatric population. 2

3 Present Solutions Provide an incentive and requirement: pediatric exclusivity (the Written Request Process in the US) and data protection (in Europe) Require pediatric plans be implemented with development of products used in pediatrics Extrapolation of Efficacy if appropriate Ensure ethical oversight Make the process and the data generated from the process transparent Additional emphasis on safety assessments 3

4 How product development is different for children Adult product development: Industry driven FDA does have authority to require post-marketing studies Pediatric product development: Government driven The Written Request: Issued by FDA. Incentive If sponsor does what FDA requests A Requirement Component-Related to submissions for adult indication which has a pediatric counter-part Pediatric information is more public Pediatric program has additional safety component 4

5 Why Is a Pediatric Focused Safety Review Important? Pediatric Studies are small in size Even more of the Pediatric population will be exposed post-marketing as there is a much higher off-label use in pediatrics There are many subpopulations and studies seldom include them all Even with small numbers, controlled trials have shown up to 20% of the time a new pediatric specific or higher incidence of adverse event 5

6 Discovery / Screening Review Post-marketing New Drug Development Pre-IND Synthesis and Purification Phase 1 Phase 2 IND Clinical Studies Phase 3 This is when Pediatrics is often discussed NDA Animal Testing Short-term Long-term AP Avg: 5-7 yrs Avg: 6-7 yrs Avg: 1 yr - Standard Avg: 6 mo - Priority 6

7 Pediatric Focused Safety Review- 1 year after labeling Congressional mandate The process involves public discussion The Pediatric Advisory Committee The web posting of safety reviews Summary of results thus far: 135 products have been reviewed Additional pediatric safety information requested to be added to label = 20% 7

8 Pediatric Safety statistics since FDAAA 2007 PAC Safety Reporting 9/27/07-12/09 5 meetings; n=46 drug products PAC discussion and action recommendations 25 Return to routine monitoring 6 Led to changes of labeling, Medication Guide or Patient Package Insert (PPI) 6 Continued monitoring or further analysis 9 Recommended labeling change, no changes yet* (Abilify, Aldara, Artiss, Asmanex, Derma-Smoothe, Diovan, Provigil, Serevent, Ventolin) *3/9/10 8

9 Projected Future Reviews to PAC (n=8) 2007 (n=9) 2008 (n=15) 2009 (n=27) planned 2010 (n=44) anticipated Pediatric safety reviews follow-up reports 9

10 BPCA and PREA: Lessons Learned Out of 385 products studied through June 2010: Efficacy not established/ data insufficient to recommend pediatric use: 69 Safety profile may differ between pediatric and adult patients: 72 (19%) 10

11 Limitations of Present Process Adverse Event Reporting system (AERS) Passive System Content of report usually limited Massive Under-reporting Limited ability to gather additional information No Query capabilities re proactive surveillance 11

12 Frustration The pediatric Advisory Committee members have repeatedly requested 1) better data 2) some form of a denominator 3) additional information not available from present system 12

13 How Can YOU Help? The Pediatric Safety program needs resources that can do the following: Provide data that has age down to months and weeks for neonates Provide information on indications that are pediatric specific Provide information on pediatric specific parameters such as growth and development 13

14 How Can YOU Help? continued Provide data on in-patient and out-patient events with specific needs for information from neonatal ICUs, pediatric ICUs, pediatric subspecialty clinics and pediatric emergency room visits Ideal system would also be able to address specific prospective initiatives = based on a high level protocol, data would be collected prospectively on adverse events and specific therapies. Confirmation would be possible from medical records 14

15 Goals Provide a clear picture of what FDA s PEDIATRIC needs in this area are Obtain a better idea of what systems exist that might be able to address some of these pediatric needs Develop a dialogue for ongoing future pediatric queries or projects Encourage you to participate in the pediatric advisory committee s safety assessments 15

16 So Where are we now? 16

17 FDA Homepage Drug Information Association 17

18 OPD Homepage Drug Information Association 18

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