1. 1 ClinicalTrials.gov PL 110-85 Implementation Nick Ide Chief Architect, ClinicalTrials.gov National Library of Medicine (Contractor) May 12, 2008

2. 2 Basic Results By September 27, 2008 –Demographic and baseline characteristics –Number of dropouts –Primary and secondary outcomes –Point of contact –Certain agreements (Restrictions on PI to discuss or publish results)

3. Data Standards NIH and FDA reviews have not identified data standards directly applicable to summary results ICH E3 is insufficiently structured and unspecific CDISC SDTM is patient level Summary requires thoughtful rollup Intellectual exercise, not blind calculation Ongoing discussions with FDA, CDISC, CTSA groups, and others to coordinate efforts

4. Overall Approach Web based data entry system Structured data Results tables similar to those in journal articles Use registry data to “pre-populate” key elements of results record –Data can be edited or changed, as necessary (with public tracking of changes) New information can be provided interactively or via XML upload

5. Challenges and Goals Need to accommodate full range of study designs and data types Need for structure to optimize data quality and search capabilities, and to allow for control over data display Need to be usable by full range of international trial community –Large data providers (e.g., drug companies, NIH ICs) –Academic medical centers –Individual investigators Must accommodate existing practice, even if not considered to be “best practice”

6. Design Features Tables are “constructed” by the data provider –Columns are pre-set as study arms, but can be changed by the data provider –Rows are measures—some are pre-set, others are customized for each study –Types of measure determines specific design of “cells” Attempt to balance fixed structure with flexibility

7. 7 Basic Results Tables Participant flow –Number started, completed, dropped out by arm Demographic and baseline characteristics –Participant description, overall and per arm Values for primary and secondary outcomes –By arm (“comparison group”) –Scientifically appropriate tests of statistical significance

8. 8 Published Participant Flow Source: Kimmick GG et al. Breast J. 2006 Mar-Apr;12(2):114-22.

9. 9 Participant Flow Number entered study Number completed study Number not completed study Other details –Phase specific information –Study specific information –Number achieved milestones, as specified by registrant

10. Information Provided By: Unique Protocol ID: Brief Title: NCT ID: Wake Forest University 1234 Sertraline for Hot Flashes NCT12756000

11. 66 women were enrolled and 4 withdrew prior to randomization.

15. 15 Published Baseline Data Source: Kimmick GG et al. Breast J. 2006 Mar-Apr;12(2):114-22.

16. 16 Demographic & Baseline Characteristics Commonly used measures –Age (continuous and categorical) –Gender –Race/Ethnicity –Region of enrollment Measures specific to each trial For each measure –Name of measure –Value, total and by arm –Names and values of categories, if categorical –Measure of dispersion, if continuous

19. 19 Measurement Types Continuous (Years) Multiple Categories

21. Menopausal Status Baseline # of Subjects Pre Post 7 55 2 27 5 28

22. 22 Published Primary Outcome Source: Kimmick GG et al. Breast J. 2006 Mar-Apr;12(2):114-22.

23. 23 Outcomes Pre-specified primary and secondary outcome measures from registry For each measure –Description –Units –Value by arm or other comparison group Names and values for categories, if categorical Measure of dispersion, if continuous Other details if time to event –Statistics (cont. next slide)

24. 24 Outcomes Statistics (cont.) –Test of non-inferiority? (y/n) If yes, other details –For each p-value provided Name of test (e.g., Chi-squared, ANOVA) Other details/comments –For each confidence interval provided % (e.g., 95% confidence interval) Name of estimate (e.g., OR, RR) Value of estimate Other details/comments

25. Information Provided By: Unique Protocol ID: Brief Title: NCT ID: Wake Forest University 1234 Sertraline for Hot Flashes NCT12756000

26. 54

28. 0.03

31. 31 DateData EntryData Display May, 2008Requirements analysis complete Post Mock-up Begin development June, 2008Prototype of data entry system Alpha Version August, 2008Beta Version of data entry system Beta Version September 27 th 2008 Public Release Timeline

32. 32 Thank you Email LISTSERV and other information: http://prsinfo.clinicaltrials.gov/fdaaa.html Email: register@clinicaltrials.gov