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

2. 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

3. Data Management
Clinical Operations
Who
Programming
Biostatisticians

6. 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%.

7. Why
Submissions

8. FDA ESG 2006-2014 Total Submission Statistics*
Submissions (US)
2013 PDUFA Performance
FDA ESG 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.

9. 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.

10. 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.

11. 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.


12. Where
North America
Europe
Japan

13. 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.

14. Data Standards
what
Data Management

15. 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

16. 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.

17. 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

18. 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

19. Case 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.

20. 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)

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

22. Case 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?

23. Enforceable Data Standards

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

25. HOW
Going Global

26. 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

27. Future
WhEN
Current

28. Current Status

29. Future

30. 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.

31. 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: 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:
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:
"Clinical Data Standards Explained." . California Health Care Foundation, 1 Nov Web. 1 July <
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:

32. Questions? Vincent J. Amoruccio, M.A. Director, Functional Head
Clinical & Statistical Programming
Alexion Pharmaceuticals, Inc.
352 Knotter Drive,
Cheshire, Connecticut 06410
(203)