Going Global Vincent J. Amoruccio, M.A. How Data Standards Can Improve the Management of Trial Data Across Borders

Introduction How Can Data Standards Improve the Management of Trial Data Across Borders ? Biostatisticians Programmers Data Managers Clinical Operations Who Submissions Why US EMA Canada PMDA Where Data Management Data Standards What Global Acceptance How Current Future When

Data Management Clinical Operations Who Programming Biostatisticians

Pharmaceutical Industry: Top 15 by Revenue The global pharmaceuticals market is worth US$300 billion a year, a figure expected to rise to US$400 billion within three years. The 10 largest drugs companies control over one-third of this market, several with sales of more than US$10 billion a year and profit margins of about 30%.

Why Submissions

FDA ESG 2006-2014 Total Submission Statistics* Submissions (US) 2013 PDUFA Performance FDA ESG 2006-2014 Total Submission Statistics* FDA is responsible for protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.

Number of Patent Lists Received (Fiscal Year) * Submissions (Canada) Number of Patent Lists Received (Fiscal Year) * Health Canada is the Federal department responsible for helping Canadians maintain and improve their health, while respecting individual choices and circumstances.

Human Use Submission Statistics* Submissions (Europe) Human Use Submission Statistics* The European Medicines Agency is a decentralized agency of the European Union, located in London. The Agency is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union.

New Drug Applications (Fiscal Year) * Submissions (Japan) New Drug Applications (Fiscal Year) * PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labor and Welfare to assure safety, efficacy and quality of pharmaceuticals and medical devices.
 PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labor and Welfare to assure safety, efficacy and quality of pharmaceuticals and medical devices.


Where North America Europe Japan

Pharmaceutical Industry: Top 15 by Location It is predicted that North America, Europe and Japan will continue to account for a full 85% of the global pharmaceuticals market well into the 21st century.

Data Standards what Data Management

Clinical Data Management Improvements The process of collection, cleaning, and management of subject data in compliance with regulatory standards. The primary objective is to provide high-quality data by minimizing the number of errors and missing data and gather maximum data for analysis. Shorten Clinical Trial Life Cycle: Technology Quality Time

Data Standards Should a patients gender be reported as “Male” or “M”? What information should be reported for vital signs? What is a data standard? An agreed upon set of rules that allow information to be shared and processed in a uniform and consistent way.

CDISC Terminology CDASH SDTM ADaM CDISC is a global, open, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of clinical research data and metadata. The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.  The CDISC vision is to inform patient care and safety through higher quality medical research in a timely and efficient way. CDISC Terminology CDASH SDTM ADaM An agreed upon set of rules that allow clinical data to be collected, reported, and analyzed in a uniform and consistent way

Findings - CDISC Standards: CDISC Case Study: With Gartner to assess the business value of the CDISC Standards Stage 1 Interviews were conducted with big Pharma, CROs, and FDA Stage 2 Top-down estimate of potential savings to pharmaceutical industry Stage 3 Bottom-up estimate of potential saving for a trial and submission Stage4 More rigorous interviews with a larger sampling of stakeholders in pharmaceutical industry. Findings - CDISC Standards: Help reduce the startup time of a clinical study by 70% to 90%. They improve overall time by 60%. Improve data quality. Enable integration of data. Enhance re-usability of data. Facilitate regulatory review

Case Study @ The New England Journal of Medicine: Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies The study used publicly available information from the FDA, the European Medicines Agency (EMA), and Health Canada. It compared the time for completion of the first review and the total review time for all applications involving novel therapeutic agents approved by the three regulatory agencies from 2001 through 2010. It examined the regulatory review time for 510 applications: 225 that were approved by the FDA, 186 by the EMA, and 99 by Health Canada.

Case Study @ The New England Journal of Medicine: Regulatory Review of Novel Therapeutics — Results FDA EMA Canada N 225 186 99 Review Cycles 1 2 ≥ 3 139 (61.8) 82 (36.4) 4 ( 1.8) 179 (96.2) 5 (2.7) 2 (1.1) 68. (68.7) 24 (24.2) 7 (7.1) First Time Review 303 (185, 372) 366 (310, 445) 352 (225, 420) Total Review Time 322 (218, 484) 366 (310, 447) 393 (310, 603)

Case Study @ The New England Journal of Medicine: Regulatory Review of Novel Therapeutics — Results

Case Study @ The New England Journal of Medicine: Regulatory Review of Novel Therapeutics — Conclusion For novel therapeutic agents approved between 2001 and 2010, the FDA reviewed applications involving novel therapeutics more quickly, on average, than did the EMA or Health Canada, and the vast majority of these new therapeutic agents were first approved for use in the United States. What does the FDA do differently that would account for faster review times?

Enforceable Data Standards

Data Standards in the US FDA Statements CDISC PDUFA V CDISC Requirement 1997 2004 2012 2017

HOW Going Global

How Can Data Standards Improve the Management of Clinical Trial Data? Data Management Improvements: Shorten Clinical Trial Life Cycle Time Quality Technology Data Standards: Help reduce the startup time of a clinical study by 70% to 90%. They improve overall time by 60%. Improve data quality. Enable integration of data. Enhance re-usability of data. Facilitate regulatory review

Future WhEN Current

Current Status

Future

Going Global Conclusion How Can Data Standards Improve the Management of Trial Data Across Borders ? Improve Data Management through time, quality, and technology. Identify a need for a global data standard Identify a global standard Adopt a globally accepted data standard Implement the data standard Make the data standard a requirement Invoke change! Solidify enforceable data standards in Europe, Japan, and the entirety of the global market! CDISC improves time, quality, data integration and re-usability. CDISC is enforceable in the US and should be enforceable globally. CDISC partners with HL7, ISO, and JIC.

References Kush, Rebecca. "Current status and future scope of CDISC standards." CDISC Journal: 1-8. Web. 1 July 2014. Downing, A.B., Nicholas S., Jenerious A. Aminawung, M.D., M.P.H., Nilay D. Shah, Ph.D., Joel B. Braunstein, M.D., M.B.A., Harlan M. Krumholz, M.D., and Joseph S. Ross, M.D., M.H.S.. "Regulatory Review of Novel Therapeutics - Comparison of Three Regulatory Agencies." New England Journal of Medicine: 2284-2293. Web. 25 June 2014. Lu, Zhengwu, and Jing Su. "Clinical Data Management: Current status, challenges, and future directions from industry perspectives." Open Access Journal of Clinical Trials: 93-105. Richesson, Ph.D., MPH, Rachel L. , and Jeffrey Krischer, Ph.D.. "Data standards in Clinical Research: Gaps, Overlaps, Challenges and Future Directions." Journal of American Medical Informatics Association 14: 687-696. "Clinical Data Standards Explained." . California Health Care Foundation, 1 Nov. 2004. Web. 1 July 2014. <www.calinxstandards.org>. Adams, Vincanne, Suellen Miller, Sienna Craig, and Michael Varner. "The Challenge of Cross-Cultural Clinical Trials Research: Case Report from the Tibetan Autonomous Region, People's Republic of China." Medical Anthropology Quarterly 19: 267-289.

Questions? Vincent J. Amoruccio, M.A. Director, Functional Head Clinical & Statistical Programming Alexion Pharmaceuticals, Inc. 352 Knotter Drive, Cheshire, Connecticut 06410 (203) 439-9623 AmoruccioV@alxn.com