Pediatric Drug & Medical Device Development: Setting Specifications & Defining Expectations

Purpose, Vision and Expected Outcomes

February 26, 2009

Carole Marcus, MBBChCo-Chair

Pediatric Drugs and Devices SubcommitteeCTSA Consortium Child Health Oversight Committee

Meeting Purpose

To formulate specifications for a national child health clinical research infrastructure to effectively and efficiently develop drugs and medical devices for children

Lack of Pediatric Information• ~ 80% of listed medication labels

disclaimed usage or lacked dosing information for children

– Physician’s Desk Reference 1973 & 1991 surveys

• Only 20-30 % of drugs approved by the FDA are labeled for pediatric use

– 1984-1989* survey, 1991-2001 repeat survey

• Only 38% of new drugs potentially useful in pediatrics were labeled for children when initially approved

– *1991-1997, FDA statistics

3Allergy/asthma

8Steroids

13Respiratory

13Antibiotics

13Sedation/anesthestics

17Immunologic/rheumatologic

18Metabolic

21Antifungals/antiparasitics

21Anticonvulsants

25Endocrine

30Antivirals

32Analgesics

36Psychiatric

38Neurology

40Hematology

44Derm/eye/ear

44Antidotes

54Gastroenterology

57Cardiac

Percent Off-LabelClass of Medications

Off-Label Status of Medication AvailableFor Pediatric Use, by Class

Need For Pediatric Drug Development

Yoon, Clin Pediatr 2006; 45:75

Need For Pediatric Medical Device Development

Pediatric Considerations

• Children are currently underserved by the medical/scientific community

• Clinical research requirements for children are different than those for adults

What CTSA’s Bring To The Table

• Intellectual and academic input and experience• Patient resources (common and rare diseases)• Infrastructure for research:

– Clinical research space– Laboratory resources– Clinical core facilities

• Development of central core facilities and informatics

• Education and training opportunities

Pediatrics In The CTSA

• 37 of 38 CTSA’s have a pediatric component• 34 of the 38 CTSA’s sent pediatric

representatives to the 2008 Child Health Oversight Committee meeting.

Current Problems With Pediatric Academic Multicenter Studies

• IRB delays• Technology transfer delays• Scientific review delays

Process for Opening a Clinical Trial

Dilts, J Clin Oncol 2006; 24:4545

Dilts, J Clin Oncol 2006; 24:4545

Mean Number Of Days Per Process

0 50 100 150 200 250 300

Start to 1st process

IRB

Contracts & grants

Scientific review committees

Receipt to open

Open to 1st subject

Receipt to 1st subject

58

69

100

105

189

73

251

Mean time (days)

Today’s Goals

• The expected deliverable will be information and specifications on the infrastructure features and parameters for a national pediatric clinical and translational platform.

Workshop Expectations

• There is no expectation to achieve consensus or solve problems, but to provide guidance and information to help develop the most responsive infrastructure.

What We Are Not Going to Do!

• Discuss specific drug/device needs• Discuss funding mechanisms• Prioritize areas of research• Discuss regulatory issues Separate meetings / activities on many of

the above are planned by NIH.

Specific Topics For Discussion

Legal And Financial

• Use of templates and common documents for intellectual property issues

• Development of policies for intellectual property, data sharing and publication

• Development of policies for confidential information sharing and disclosure

• Potential mechanisms for cost sharing• Privacy and protecting health information

FDA and OHRP Regulatory Support

• Regulatory support and regulatory resources

• Regulatory reporting information flow and responsibilities

• Interest and ability to hold IND’s and IDE’s

Availability And Development Of Core Facilities

• Analytic services:– Pharmacokinetics– Pharmacogenomics– Pharmacodynamics– toxicology

• Specimen analysis• Specimen repository• Certification of core facilities

– GLP– CLIA

Pediatric-specific Biostatistical Resources

• Longitudinal analyses• Incorporation of growth parameters into

statistical assessments• Small sample sizes

Informatics Needs

• Use of data coordination centers• Use of data standards for data

acquisition, data transmission and data storage, to ensure interoperability

• Data security procedures

Pediatric-specific Ethical Issues

• Guidelines for what constitutes minimal risk; criteria for referring protocols for 407 review

• Use of harmonized age-appropriate assent templates

• Guidelines for re-consenting pediatric enrollees in long term studies

Bridging the Gap From Clinical Care To Research

• Approaches to integrate participation in clinical trials with clinical care

• Tools to inform families about pediatric clinical research

• Recruitment and retention policies including inclusion of underrepresented populations

• Outreach efforts• Sharing of results with study participants and

the general public (e.g., clinicaltrials.gov)

Performance Metrics

• Plans to develop, implement and assess performance metrics

• Time to opening of study / enrollment of 1st subject

Logistical Considerations

• Need for a single point of contact for general information for network activities

• Need for public web site; which elements to include

Building A Culture Of Product Development

• Encourage product development in addition to pursuit of non-product development scientific agendas

• Anticipated training needs for consortium personnel to address these needs

What To Expect From NIH

• Willingness to learn and adapt• Commitment to the highest scientific and ethical

standards• Willingness to collaborate and cooperate with

partners, patients, study participants and the public

• Interest in participating in the development of products with clinical benefit for children

Steven Hirschfeld, MD, PhD