Critical Path Public Docket: Overview for the FDA Science Board

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Critical Path Public Docket Overview for the
FDA Science Board

• November 5, 2004

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priority Hurdles
• Other Messages
• For More Information

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Overwhelming Support

• Overwhelming Concurrence With Critical Path
  Diagnosis recognition of science infrastructure
  problem.
• Overwhelming Concurrence With CP Rx Initiative
  focus on research, science-based standards, and
  collaboration.

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Overwhelming Support

• We Heard This From drug industry and groups,
  patient groups, device companies and groups,
  biotech companies, others.
• Recognition of Unique FDA Role "FDA stands at
  the gateway between the research laboratory and
  the patient's bedside, FDA is uniquely positioned
  to understand the scientific and regulatory
  hurdles associated with bringing innovative
  medicines to the marketplace. -- PhRMA

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What Patients are Telling Us

• FasterCures is strongly supportive of and
  encouraged by the FDAs new Critical Path
  Initiative. This effort has the potential to
  contribute to the goal of saving lives by saving
  time in making new therapies available for use
  sooner. -- FasterCures
• We heartily endorse the FDA for its
  leadership in launching the Critical Pathway
  Initiative. -- Prostate Cancer Foundation

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What Patients are Telling Us

• We particularly welcome the Critical Path
  Initiatives attention to improving models and
  technology for enhancing the clinical relevance
  and predictive value of preclinical assays,
  especially those related to pharmacology and
  toxicology. -- AIDS Treatment Activist
  Coalition
• We commend you for the serious effort you are
  making to resolve the dilemma we face, and offer
  you our support and help as we address these
  challenging questions. -- National Osteoporosis
  Foundation

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What Industry Is Telling Us

• AdvaMed compliments FDA on this effort to
  develop an organized approach to identifying
  impediments to and improving the process by which
  we bring medical products to market. We remark
  particularly on the recognition that there is
  more to speeding up the overall process of
  getting a product to market than simply revising
  the FDA review and approval process.
• -- Advamed
• Baxter applauds the initiative taken by FDA in
  publishing its report, and is supportive of
  potential collaborative efforts between industry,
  academia, and FDA" -- Baxter

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What Industry Is Telling Us

• A new product develop toolkit is urgently
  needed to improve predictability and efficiency
  along the Critical Path. We appreciate the
  Agencys efforts to take the lead on this
  initiative --Johnson Johnson
• "BMS agrees with the agencys overall goal of
  creating a new generation of performance
  standards and predictive tools that will provide
  better information about the safety and
  effectiveness of an investigational product at an
  earlier stage in the drugs development.
• -- Bristol-Myers Squibb Co.

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Call For FDA Action

• Submitters call for FDA to undertake research,
  develop guidances, initiate collaborations, and
  convene consensus development activities on a
  wide range of scientific issues.
• Docket submitters offer to work with FDA.

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Demand Exceeds Supply

• Docket Demand for FDA Action Exceeds FDA
  Capacity Far more proposed than FDA can
  undertake.
• Principles for setting priorities for FDA
  actions are on Science Board agenda.

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priorities
• Other Messages
• For More Information

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Caveats and Cautions

• This Docket Overview Is Not Comprehensive
• Major themes
• Flavor of specifics
• Docket Is Not the Only Source of Input

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priorities
• Other Messages
• For More Information

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Overriding Concerns

• Clinical Trials
• Biomarkers and Endpoints

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Clinical Trials

• New Statistical Tools and Analytic Methods to
  Support Innovative Trial Design
• Bayesian methods, methods for imputing missing
  data
• Adaptive designs, non-inferiority designs, proof
  of concept trials, enrichment designs
• Modeling and Simulation, looking for first steps

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Clinical Trials

• Standardization of Trial Administration
• Data collection and submission
• Investigator contracts
• IT Issues -- encourage development of
  electronic tech for data collection, monitoring,
  and reporting

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Clinical Trials

• Disease-specific trial protocols
• Patient recruitment, enrollment, and
  retention
• Consortiums and registries
• Collaborations with NIH and others
• Harmonization of IRB and consent requirements

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Clinical Trials

• Alternative approaches to clinical trials for
  performance of bacterial detection devices.
• Create epilepsy clinical trial consortium.
• Create career model for clinical researchers.
• Articulate how FDA views use of inadequate
  therapies as controls.
• Educate public about value of trial
  participation.

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Biomarkers / Endpoints

• Getting to Yes Clarify Process for Validating
  Surrogate
• Clarify Steps and Evidence for Using Biomarkers
  for Other Purposes
• Work to Establish Biomarkers for Specific
  Conditions

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Biomarkers / Endpoints

• Requests to publish lists of biomarkers
• Diagnostic markers that may be used to enrich
  study designs
• Promising or valid pre-clinical biomarkers,
  including biomarkers from gene expression studies
  in animals
• Guidance on accepting post-approval studies to
  validate biomarkers
• Standards/guidance on imaging as biomarker

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Biomarkers / Endpoints

• Numerous requests for FDA to work with
  stakeholders to identify better endpoints in
  specific conditions sepsis, SLE, diabetes,
  Alzheimers, variety of cancers, obesity, aging,
  CF, epilepsy, infectious diseases.
• Patient-centered endpoints.

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priorities
• Other Messages
• For More Information

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Submissions Ask for Attention to Wide Array of
Conditions

• Alzheimer's disease, lupus, scleroderma, cancer
  in general, prostate cancer, pancreatic cancer,
  infectious diseases, cystic fibrosis,
  cardiovascular disease, epilepsy, metabolic
  diseases/diabetes, osteoporosis, gastroesophageal
  reflux disease, Parkinson's disease, obesity,
  rare disorders in general, MS, sepsis, HIV/AIDS,
  irritable bowel syndrome, ALS, stroke,
  gastrointestinal diseases in general.
• Pediatric Therapies

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Cancer

• New approaches to clinical trials (alternative
  study designs and streamlined administration)
• Identify and validate new biomarkers and
  surrogate markers.
• Need for public-private partnerships to boost
  trial participation, develop plan on specific
  cancers

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Cancer

• Validate PET for tumor progression
• Allow testing earlier in disease
• Prioritize oncology drugs for study in
  pediatric population
• Move away from survival as primary endpoint

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Other Priority Hurdles

• In Vitro Diagnostics
• Data Pooling / Mining, and Models
• Mining FDA-held Data
• International Harmonization
• Antibiotics

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Other Priority Hurdles

• Modeling/Simulation
• Path for Combination Products
• Industrialization of Biologics
• Medical Countermeasures Against Bioterrorism

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priorities
• Other Messages
• For More Information

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Regulatory Messages

• CP must not substitute for improvements to
  review process
• New CP tools should replace old ones, not
  constitute new requirements
• Clarify regulatory pathways for certain types
  of products (e.g. combination products, tissue
  engineered products)

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Guidances Messages

• Do More
• Do Them Faster
• Keep Them Up To Date
• Use Collaborative Process

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Communications Messages

• Lack of consistency within and across
  divisions, and over time
• Create venues for collaboration
• More, earlier meetings with FDA

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Resources Messages

• Do Not Divert Resources From Review
• Adequate/Consistent Staffing
• Does FDA Have Enough?

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Presentation Overview

• Themes
• Caveats and Cautions
• Biggest Concerns
• Other Priorities
• Other Messages
• For More Information

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For More Information

• Start at FDA website (www.fda.gov)
• Click on the Dockets link
• On Docket web page, go to Dailies
• Click on 2004
• Under docket 2004N-0180, click on the
  individual days to view CP comments. (The system
  will not display a cumulative view of
  submissions.)

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For More Information

• http//www.fda.gov/oc/initiatives/criticalpath/