1. Snapshot of the Clinical Trials Enterprise as revealed by ClinicalTrials.gov
Content downloaded: September 2012

2. Background
Information on ClinicalTrials.gov and the creation of the AACT database is available at:
The following slides include data from the 2012 ACCT database update with an analysis of studies registered and results reported at ClinicalTrials.gov

3. 2012 Update of the Database for the Aggregate Analysis of ClinicalTrials.gov (AACT)
Design
Downloaded XML dataset of all clinical studies from ClinicalTrials.gov on September 27*, 2012
Designed and implemented relational database to facilitate aggregate analysis of registration and results data
Uses of Aggregate Data
Examine the “Clinical Research Enterprise”
Provide information to specific user communities
Examine the quality and completeness of reporting
*Includes studies publicly released by ClinicalTrials.gov through 25 September 2012

4. Studies registered at ClinicalTrials.gov
Studies included in Sep 2012 download
N=133,128
Interventional Studies
N=108,113
Registered prior to Oct 2007
N=38,334
Registered on/after 1 Oct 2007
N=69,779
Observational Studies
N=24,407
Expanded Access Studies
N=181
Study Type not applicable
N=427
Snapshot analysis is focused on these studies.

5. Overview of study registration
Funding
Study Phase
Intervention Types

6. Funding Derived as follows: Submitted information Derived Lead Sponsor
Collaborators
Funding
Industry
No restrictions
Not NIH
At least one from Industry, none from NIH
NIH
Not industry
At least one from NIH
Not industry, not NIH
None from industry, none from NIH
Other

7. Study registration by funding

8. Study registration by study phase

9. Study registration by funding and phase

10. Study registration across intervention types
A study may have more than one intervention type
N=1 study did not report intervention type information

11. Study registration across intervention types
Studies of drugs, biologics and devices in phases 2-4 are required to be registered by FDAAA.
+ Includes behavioral, radiation, dietary supplement, in addition to other interventions
N=1 study did not report intervention type information

12. Study registration by intervention type and phase
Studies of drugs, biologics and devices in phases 2-4 are required to be registered by FDAAA.
+ Includes behavioral, radiation, dietary supplement, in addition to other interventions
N=1 study did not report intervention type information

13. Sites and participants for registered studies
Single- and multi-center studies
Number of sites for multi-center studies
Location of sites
Eligibility: sex
Eligibility: age restrictions and exclusions

14. Registration of single- and multi- center studies
Single-Center
Multi-center
N=4,784 studies did not report information about number of centers

15. Registration of single-center and multi-center studies by phase
N=4,784 studies did not report information about number of centers

16. Median number of sites/study for multi-center studies
Based on N=22,006 multi-center studies with information about number of sites

17. Study Registration by Location of Study Sites
N=3,981 studies did not report information about location of study sites
A study can have sites in multiple regions. Location information based on the address of facilities listed in the study record, and countries where sites were previously listed but removed from the current study record. Regions are defined according to
Central and South America combined into C&S America. Pacifica, and East, North, South, and Southeast Asia combined into Pacifica/Asia.

18. Studies with Sites in U.S. and Rest of World (R.O.W.)
N=3,981 studies did not report information on U.S. locations

19. Studies by U.S. location by Funding
Studies with at least 1 US site
Studies with only non-US sites
N=3,981 studies did not report information on U.S. locations

20. Study Registration by Sex Eligibility
N=1 study did not report information on sex eligibility

21. Age Restrictions for Registered Studies
+ All but 1 study under consideration (N=69,778) provided information on minimum and maximum age restrictions, although some indicated that there were no restrictions (responded “N/A”). The % of studies with restrictions was calculated among all studies.

22. Age Exclusions for Registered Studies
+ All but 1 study under consideration (N=69,778) provided information on minimum and maximum age restrictions, although some indicated that there were no restrictions (responded “N/A”). The % of studies with restrictions was calculated among all studies.

23. Design Characteristics of Registered Studies
Primary Purpose
Number of arms
Randomization
Masking — knowledge of intervention assignments (open label, single-blind, or double-blind)
Enrollment
Study duration
Data Monitoring Committee — whether a data monitoring committee was appointed for this study

24. Primary Purpose for Registered Studies
N=4,690 studies did not report primary purpose
+ Includes the categories supportive care, screening, health services research, and basic science

25. Primary Purpose by Phase
N=4,690 studies did not report primary purpose
+ Includes the categories supportive care, screening, health services research, and basic science

26. Number of Arms for Registered Studies
N=1,978 studies did not report information on number of arms and 2 studies reported no arms

27. Number of Arms by Phase
N=1,978 studies did not report information on number of arms and 2 studies reported no arms

28. Use of Randomization in Studies with >1 Arm
N=257 studies with >1 arm did not report randomization information

29. Use of Randomization by Phase in Studies with >1 Arm
N=257 studies with >1 arm did not report randomization information

30. Use of Masking in Randomized Studies with >1 Arm
N=154 randomized studies with >1 arm did not report masking information

31. Use of Masking by Phase in Randomized Studies with >1 Arm
N=154 randomized studies with >1 arm did not report masking information

32. Number of Subjects/Study for registered studies (Anticipated or Actual enrollment)
N=743 studies did not report enrollment

33. Median Enrollment by Phase for Registered Studies
N=743 studies did not report enrollment

34. Median Enrollment by Funding for Registered Studies
N=743 studies did not report enrollment

35. Study Duration by Phase for Registered Studies
Study duration presented as months from study start to completion of follow up for primary endpoint. Calculations based on anticipated primary completion date if actual date not reported.
N=3054 studies did not report start date and/or primary completion date

36. Study Duration by Funding for Registered Studies
Study duration presented as months from study start to completion of follow up for primary endpoint. Calculations based on anticipated primary completion date if actual date not reported.
N=3054 studies did not report start date and/or primary completion date

37. Use of Data Monitoring Committee (DMC)

38. Use of DMC by Phase

39. Regression Analyses of DMC use, Blinding, and Randomization
Associations Between Study Characteristics and DMC use, blinding, and randomization
Logistic regression analysis of
DMC use (yes versus no)
Blinding (single- or double-blind masking versus unblinded)
Randomization (yes versus no or NA: single-arm)

40. DMC Use: Multivariable Odds Ratios
Odds Ratio (95% CI)
Phase
(vs. Phase 3)
Funding
(vs. Industry)
Purpose
(vs. Treatment)
Intervention
(vs. Drug/Biological)
* Per 1000 participants; # Per increment of 2 yrs; + Includes supportive care, screening, health services research, and basic science

41. Blinding: Multivariable Odds Ratios
Odds Ratio (95% CI)
Phase
(vs. Phase 3)
Funding
(vs. Industry)
Purpose
(vs. Treatment)
Intervention
(vs. Drug/Biological)
* Per 1000 participants; # Per increment of 2 yrs; + Includes supportive care, screening, health services research, and basic science

42. Randomization: Multivariable Odds Ratios
Odds Ratio (95% CI)
Phase
(vs. Phase 3)
Funding
(vs. Industry)
Purpose
(vs. Treatment)
Intervention
(vs. Drug/Biological)
* Per 1000 participants; # Per increment of 2 yrs; + Includes supportive care, screening, health services research, and basic science

43. Reporting of basic results and events
Number of participants at baseline
Race and ethnicity
Outcomes
Adverse and other events

44. Results Reporting by Study Registration Date and Funding
Studies that report results also report at least one data element for the following elements: Results Point of Contact, Participant Flow, Baseline Data (Number of Participants, Age (except for 2 studies), Gender (except for 2 studies)), and results for at least one Primary Outcome.

45. Number of Studies Reporting Results by Phase and Funding

46. Median Time to Reporting Results by Phase and Funding
Time to reporting results is calculated as months from primary completion date to the date results were first received by ClinicalTrials.gov
N=32 studies with results did not report primary completion date
N=5 Phase 0 studies excluded from the graph.
Median for NIH Phase 1 based on 1 study.

47. Median Number of Participants at Baseline by Phase and Funding for Studies with Results
N=5 Phase 0 studies excluded from the graph. Median for NIH Phase 1 based on 1 study.

48. Reporting of Participant Race at Baseline by Funding among Studies Reporting Results
OMB=Office of Management and Budget categories

49. Reporting of Participant Ethnicity at Baseline by Funding among Studies Reporting Results
OMB=Office of Management and Budget categories

50. Reporting of Secondary Outcome Results by Phase for Studies Reporting Results
All studies reporting results also reported results for at least one primary outcome.
Graph excludes N=5 studies in Phase 0 that report results

51. Reporting of Secondary Outcome Results by Funding for Studies Reporting Results
All studies reporting results also reported results for at least one primary outcome.

52. Reporting of Adverse Events by Phase for Studies Reporting Results
AE = Adverse Event; SAE = Serious Adverse Event
Graph excludes N=5 studies in Phase 0 that report results

53. Reporting of Adverse Events by Funding for Studies Reporting Results
AE = Adverse Event; SAE = Serious Adverse Event
All SAEs, and all non-serious AEs with >5% frequency within at least one arm or comparison group must be reported for trials that meet reporting requirements.

54. Funding Disclosure
Financial support for this work was provided by grant U19FD from the U.S. Food and Drug Administration awarded to Duke University for the Clinical Trials Transformation Initiative