# Presentation: 075701

## Session 1Background and Legislative Requirements

## ClinicalTrials.gov Background

- Dr. Deborah A. Zarin

## ClinicalTrials.gov Team

**Director**
- Deborah Zarin
**Project Leads**
- Annice Bergeris
- Nicholas Ide
- Alison Robbins
- Tony Tse
- Rebecca Williams
**Quality Assurance**
- John Frye
- Cherryl Macalintal
- Alex Valentine

**Systems Development**
- Jane Fun
- John Gillen
- Alex Kostyukovsky
- Russell Loane
- Allison Yu
**Domain Expert**
- William Harlan
**Administration**
- Tamia Whitfield

- Jerry Sheehan

- Betsy Humphreys

## Ethical and Scientific Rationale for Increased Clinical Trial Transparency

- Subjects put themselves at risk
- Subject’s right to be informed
- All available options, including ongoing trials
- Previous research, including completed trials
- Avoid redundant trials
- Support Evidenced-Based Medicine (EBM)
- Detect reporting problems
- Lack of publication
- Unexplained changes to protocol

## Recent Events: Lack of Transparency in Clinical Research

## Source: Figure 1A. Turner et al. (NEJM, 2008)

## ...although the ENHANCE trial ended in April 2006, the data had not yet been released. 

- The investigation was launched following concerns...

- ...although the ENHANCE trial ended in April 2006, the data had not yet been released.

- ...[the sponsors] did not register the clinical trial in a timely manner.

- ...[the sponsors] attempted to change the study endpoints, and thus the study results, prior to the public release of the results.

## Source: Silverstein FE et al. JAMA. 2000 Sep 13;284(10):1247-55.

## Kaplan-Meier estimates for ulcer complications according to traditional definition. Results are truncated after 12 months, no ulcer complications occurred after this period. Adapted from Lu 2001. 

- Kaplan-Meier estimates for ulcer complications according to traditional definition. Results are truncated after 12 months, no ulcer complications occurred after this period. Adapted from Lu 2001.

- Source: Jüni P, Rutjes AW, Dieppe PA. BMJ. 2002 Jun 1;324(7349):1287-8.

## ClinicalTrials.gov

- Prospective registry
- Interventional and observational “trials”
- Approved by IRB (or equivalent)
- Conform to regulations of national health authorities
- All sponsor types
- All intervention types
- Summary of key protocol items
- Consistent with ICMJE and WHO
- Links to publications, other info
- Does not include unpublished results

## Policies and Users

**ClinicalTrials.gov**

- FDAMA 113
- BPCA

- Maine

**PL 110-85**

- Sponsor Policy
- (e.g., NIH, VA)

- ICMJE

- WHO

- Ottawa
- Statement

- Recruitment (e.g., patients, physicians)

- Journal Editors

- Research Funders

- Systematic Reviewers

- Health Policy Makers

## International Registries and Number of Trials (as of 2/4/08)

| ClinicalTrials.gov | 50,564 |
| --- | --- |
| ISRCTN (UK) | 6,514 |
| Australian New Zealand Clinical Trial Registry (ANZCTR) | 1,973 |
| Netherlands Trial Registry | 1,111 |
| UMIN Clinical Trials Registry (Japan) | 943 |
| Chinese Clinical Trial Register (ChiCTR) | 34 |
| Clinical Trials Registry – India (CTRI) | 16 |

## Characteristics of ClinicalTrials.gov

- Web-based registration system (PRS)
- Register through organizational accounts
- Key part of validation
- XML data upload (<20% records)
- Data are dynamic—”data provider” can modify data at any time
- Changes are tracked

## Homepage - ClinicalTrials.gov

## Slide 15

## Slide 16

## http://ClinicalTrials.gov/archive

## Slide 18

## ClinicalTrials.gov  General Statistics

## Slide 20

## ClinicalTrials.gov Statistics(as of 2/4/2008)

- ClinicalTrials.gov Statistics(as of 2/4/2008)

**	**					_Number__	_	_Percent_
**Total****	****	*****	******	******	*****50,564  ****	**** 100%**
**Type of Trial***
- Observational		  	  7,701	   	   15%
- Interventional			42,836	   	   85%
- Drug & Biologic			32,835
- Surgical Procedure		10,856
- Behavioral, Gene
-         Transfer, Other      		  4,809
- Device		  		  2,628
**International Sites**
**	**	US only				25,485 	     	  50%
- 		Non-US only			15,982		  32%
- 		US & Non-US mixed		  3,934	     	    8%
- 		Missing				  5,163		  10%

- * 27 records missing Study Type information

## ClinicalTrials.gov Statistics Cont.(as of 2/4/2008)

- ClinicalTrials.gov Statistics Cont.(as of 2/4/2008)

**User Statistics**
- Page Views per month		     20 Million
- Unique visitors per month 	     500,000

**	**				_Number_		_Percent_

**Trials by Data Provider**
** **
- US Federal (including NIH)	16,430   	   33%
- University, other			19,803	   39%
- Industry				14,331 	   28%

## Organizational Accounts

**Total**                  4,792
- Fed accounts       71
- NIH accounts       26
- Industry           1,783
- Other               2,912

## Validation of Data for Registry

- Issues
- Quality Assurance: Are the entries as accurate and informative as possible?
- Validation (w/o access to protocols): Is the fundamental information true?
- QA Process at ClinicalTrials.gov
- System of automated and manual checks
- Staff works with data provider to correct/improve records
- Links inserted

## Slide 25

## ENHANCE

- Source: Kastelein JJ, Sager PT, de Groot E, Veltri E. Am Heart J. 2005 Feb;149(2):234-9.

**1**

**2**

**3**

## Primary Outcome Measures:

- Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint. [ Time Frame: 24 months ]

- Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint. [ Time Frame: 24 months ]

## Legislative RequirementsJerry Sheehan