CNS Clinical Trials: Suicidality and Data Collection. Ways to Facilitate Collaboration: How and Who?

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1 CNS Clinical Trials: Suicidality and Data Collection Ways to Facilitate Collaboration: How and Who? ShaAvhree Buckman, M.D., Ph.D. Acting Director Office of Translational Sciences Center for Drug Evaluation and Research U.S. Food and Drug Administration

2 Innovation Gap NMEs (New Drug Approvals) PhRMA Member R&D Spending $ $39.40 Pharma Innovation Gap Burrill & Company

3 FDA s Response: Critical Path Initiative (CPI) The old approach is not working efficiently Change requires collaboration to capitalize on the expertise and resources of others FDA is willing and able to take the leadership role in fostering innovation

4 What is the Critical Path? There is a Critical Path of medical product development stretching from candidate identification to commercial production Involves serial evaluation of product performance through preclinical testing, clinical evaluation, and manufacturing FDA s Critical Path Initiative launched to focus on the sciences used to do these evaluations Aim to improve the efficiency of medical product development

5 FDA s Role in the CPI Develop infrastructure and tools for product development (not focus on development of specific products but rather areas of need) Encourage collaborative efforts among government, academia, industry, and patient groups Develop relevant data standards and regulations Build support for relevant academic science Create opportunities to share existing knowledge and databases

6 Examples of Collaborative Efforts Cardiovascular Safety Research Consortium Serious Adverse Events Consortium Clinical Trials Transformation Initiative Predictive Safety Testing Consortium Coalition Against Major Diseases Patient Reported Outcomes Consortium Biomarkers Consortium Sentinel Initiative

7 Cardiovascular Safety Research Consortium FDA and Duke Clinical Research Institute Academia, industry, patient advocacy groups, other government and non-profit organizations Development of ECG warehouse as a publiclyaccessible depository of waveforms that can be used to improve methodology for QT interval testing Coordinate and support research projects involving ECGs obtained in clinical trials to identify gaps in cardiac biomarkers

8 Building Data Warehouses ECG Data Warehouse Collaboration to build a repository of more than 2 million ECGs in a single electronic data warehouse Enabling academic and industry research on better markers of cardiac toxicity Result: more efficient trial conduct and improved patient safety

9 Building Data Warehouses Janus Data Warehouse Collaboration between FDA and NIH/NCI to build electronic data warehouse Improve scientific decision-making by making data more available to reviewers Improve safe use of products before and after marketing

10 International Serious Adverse Events Consortium Coordinated by Arthur Holden Goal: To identify and validate DNA-variants which are clinically useful in predicting the risk of drug induced serious adverse events Create a publicly available knowledge base Involvement of industry, government agencies, national and international academia Initial projects Stevens-Johnson syndrome (Serious Skin Reactions) Drug Induced Liver Injury (DILI)

11 Clinical Trials Transformation Initiative CTTI Collaboration with Duke University, Industry, NIH, and FDA Representation from government, industry, patient advocacy groups, professional societies, and academia Focus on clinical trials practices that, when adopted broadly, will increase the quality and efficiency of clinical trials

12 Predictive Safety Testing Consortium Coordinated by C-Path Institute 17 pharmaceutical companies represented Unprecedented sharing of potential early indicators of clinical safety Effort to share information leading to qualification of accessible biomarkers of preclinical and clinical safety Working groups Nephrotoxicity Hepatotoxicity Vasculitis Carcinogenicity Muscle toxicity

13 Patient Reported Outcomes (PRO) Consortium Coordinated by C-Path Institute Multiple medical product industries represented Purpose To develop, evaluate, and qualify PRO Instruments for use in clinical trials designed to evaluate the safety and effectiveness of medical products. Establishing coordinating committee

14 Stakeholders Pharmaceutical Companies Medical Device Companies Professional Organizations Patient Advocacy Academia Others C-Path (Neutral Ground Administrative Coordinator) PRO Consortium Executive Committee FDA (Federal Liaisons) Other Federal Agencies NIH, AHRQ, (PROMIS), CMS Work Group 1 Work Group 2 Work Group 3 Work Group 4 Instrument A Instrument B Instrument C Instrument D Review/Feedback From Partners/FDA/Others PRO Instruments Qualified for Use October 20, 2006 Data Shared in the public domain 14

15 Roles & Responsibilities for FDA FDA: Federal liaisons to PRO Consortium with no voting rights or other fiduciary role Submission of dossiers to FDA does not automatically constitute fit for purpose FDA scientists will perform independent reviews of the PRO instrument dossiers prior to making recommendations of fit for purpose, labeling claims Inclusion of PRO instruments in upcoming clinical trials must be determined between sponsor and the review division

16 Coalition Against Major Diseases CAMD Focus on Parkinson s and Alzheimer s Collaboration: C-Path and Brookings Institutes, Academic and Industry Aims to clarify natural history using shared data from placebo use (aim: natural history of the disease) Support disease modeling and improved trial efficiency

17 Biomarkers Consortium FDA/NIH/FNIH/CMS/Industry collaboration Promote the discovery, development, and qualification of promising biomarkers Executive Committee formed 4/24/06 Steering Committees in Cancer, Metabolic Disorders, Inflammation and Immunity, Neuroscience Specific Project teams for each project Public Launch 10/5/06

18 Precompetitive Collaboration Allows resource leveraging of industry, NIH and foundations Industry membership offers new capabilities for pooling samples from completed trials combined industry expertise in development piggybacking onto existing clinical trials faster progress and better generalization cost efficiency partnership with NIH, FDA and academia ability to address complex and large projects

19 Current landscape Fragmented biomarker efforts lacking coordination & direction Biomarker consortium Established to focus efforts and enable effective collaboration The Biomarkers Consortium Executive Committee [NIH / FDA / CMS / industry / general public / FNIH] Cancer Steering Committee Metabolic Disorders Steering Committee Neuroscience Steering Committee Inflammation and Immunity Steering Committee Project Team 1 Project Team 2 Project Team 3 Project Team 4 Project Team 5 Project Team 6

20 Sentinel Initiative Goal: develop a nation-wide electronic safety monitoring system Data sources remain with original owners behind existing firewalls Owners would run queries FDA-requested or other (or could opt out) and convey the results of their queries to the network for analysis according to strict privacy and security safeguards System will enable FDA to partner with existing data owners (e.g., insurance companies with large claims databases, owners of electronic health records) New system Will strengthen FDA's ability to monitor postmarket performance of a product Will augment, not replace, existing systems

21 Schematic of FDA s Vision of Sentinel

22 Current Status FDA launched the Sentinel Initiative and released an initial report on May 22, 2008 FDA is hosting a series of meetings with all stakeholder groups (e.g., federal partners, academia, data holders, public, industry, vendors) FDA is actively involved in numerous activities, both public and private, which will lend important input FDA has let a series of related contracts Governance Outreach Protecting privacy and maintaining security Technical- database models, data sources, methods, medical product uptake Public workshop held on December 16, 2008 To provide an update on the current status of the Sentinel Initiative To elicit a broad ranging discussion among all stakeholders on topics, including Potential governance models and their implications Approaches to ensuring continued involvement of all stakeholders as the initiative evolves

23 Common Themes Start with public health need Identify willingness of partners to share data pre-competitively Identify gaps/avoid duplication/ low hanging fruit Identify needed data standards as appropriate Leverage resources/expertise Identify partners: define roles/responsibilities Co-develop: proposals, timelines etc. Share data in public domain as quickly as appropriate tools

24 Summary: Critical Path Initiative and Efficient Medical Product Development Goal of CPI is reinvigorating efficient medical product development to deliver on the promise of the new science Success in the CPI will require appropriate collaboration and datasharing FDA is committed to the success of the CPI

25 CDER Office of Translational Sciences ShaAvhrée Buckman, MD, PhD (Tel)