Critical Path Public Docket: Overview for the FDA Science Board
November 5, 2004
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priority Hurdles Other Messages For More Information
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.
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
What Patients are Telling Us
“FasterCures is strongly supportive of and encouraged by the FDA’s 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
What Patients are Telling Us
“We particularly welcome the Critical Path Initiative’s 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
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
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 Agency’s efforts to take the lead on this initiative…” --Johnson & Johnson
"BMS agrees with the agency’s 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 drug’s development.” -- Bristol-Myers Squibb Co.
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.
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.
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priorities Other Messages For More Information
Caveats and Cautions
This Docket Overview Is Not Comprehensive– Major themes– Flavor of specifics
Docket Is Not the Only Source of Input
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priorities Other Messages For More Information
Overriding Concerns
Clinical Trials
Biomarkers and Endpoints
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
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
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
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.
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
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
Biomarkers / Endpoints
Numerous requests for FDA to work with stakeholders to identify better endpoints in specific conditions: sepsis, SLE, diabetes, Alzheimer’s, variety of cancers, obesity, aging, CF, epilepsy, infectious diseases.
Patient-centered endpoints.
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priorities Other Messages For More Information
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
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
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
Other Priority Hurdles
In Vitro Diagnostics
Data Pooling / Mining, and Models
Mining FDA-held Data
International Harmonization
Antibiotics
Other Priority Hurdles
Modeling/Simulation
Path for Combination Products
Industrialization of Biologics
Medical Countermeasures Against Bioterrorism
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priorities Other Messages For More Information
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)
Guidances Messages
Do More
Do Them Faster
Keep Them Up To Date
Use Collaborative Process
Communications Messages
Lack of consistency within and across divisions, and over time
Create venues for collaboration
More, earlier meetings with FDA
Resources Messages
Do Not Divert Resources From Review
Adequate/Consistent Staffing
Does FDA Have Enough?
Presentation Overview
Themes Caveats and Cautions Biggest Concerns Other Priorities Other Messages For More Information
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.)
For More Information
http://www.fda.gov/oc/initiatives/criticalpath/