Critical Path Public Docket: Overview for the FDA Science Board

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.


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



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


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


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.



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



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?



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/

http://www.fda.gov/oc/







Documents

Critical Path Public Docket: Overview for the FDA Science Board