Snapshot of the Clinical Trials Enterprise as revealed by ClinicalTrials.gov Download date: Sept 2011

Background Background on ClinicalTrials.gov and the creation of the AACT database is available at The ClinicalTrials.gov website: http://www.clinicaltrials.gov/ CTTI’s website: http://ctti-clinicaltrials.org/what-we-do/analysis-dissemination/state-clinical-trials/aact-database

2011 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*, 2011 Designed and implemented relational database to facilitate aggregate analysis of 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 2011

Studies registered at ClinicalTrials.gov Studies included in Sep 2011 download N=113,909 Interventional Studies N=92,946 Registered prior to Oct 2007 N=38,388 Registered on/after 1 Oct 2007 N=54,558 Observational Studies N=20,448 Expanded Access Studies N=145 Study Type not applicable N=370 Snapshot analysis is focused on these studies.

Overview Funding Study Phase Intervention Types

Funding Derived as follows:

Funding

Study Phase

Funding by Phase

A study may have more than one intervention type Intervention Types A study may have more than one intervention type N=1 study missing intervention type information

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 missing intervention type information

Intervention Types by 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 missing intervention type information

Sites/Participants Single- and multi-center studies Number of sites for multi-center studies Enrollment Location of sites Eligibility: sex Eligibility: age restrictions and exclusions

Single-Center and Multi-center Studies N=4,007 studies missing information about number of centers

Single-center and Multi-center Studies by Phase N=4,007 studies missing information about number of centers

Median Number of Sites/Study for Multi-center Studies Based on N=17,279 multi-center studies with information about number of sites

Number of Subjects/Study (Anticipated or Actual enrollment) N=701 studies have missing enrollment

Median Enrollment by Phase N=701 studies have missing enrollment

Median Enrollment by Funding N=701 studies have missing enrollment

Location of Study Sites N=3,378 studies have missing 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 http://www.clinicaltrials.gov/ct2/search/browse?brwse=locn_cat Central and South America combined into C&S America Pacifica, and East, North, South, and Southeast Asia combined into Pacifica/Asia

Studies with Sites in U.S. and Rest of World (R.O.W.) N=3,378 studies have missing information on U.S. locations

Eligibility: Sex

Eligibility: Age Restrictions + All studies under consideration (N=54,558) 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.

Eligibility: Age Exclusions + All studies under consideration (N=54,558) 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.

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

Primary Purpose N=3,668 studies have missing primary purpose + Includes the categories supportive care, screening, health services research, and basic science

Primary Purpose by Phase N=3,668 studies have missing primary purpose + Includes the categories supportive care, screening, health services research, and basic science

Number of Arms N=1,878 studies have missing information on number of arms and 2 studies reported no arms

Number of Arms by Phase N=1,878 studies have missing information on number of arms and 2 studies reported no arms

Randomization N=1,797 studies have missing randomization information

Randomization by Phase N=1,797 studies have missing randomization information

Masking N=1,131 studies have missing masking information

Masking by Phase N=1,131 studies have missing masking information

Data Monitoring Committee (DMC)

DMC by Phase

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)

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

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

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

Trends in Data 2007-2011 Change in Number of Trials Funding Decrease in trials funded by industry Increase in trials funded by “other” (Not industry or NIH) Type and Purpose of Trials Concomitant decrease in trials including a drug intervention, and trials with treatment as the primary purpose Trial Phase Decrease in number of trials appears to be similar across phases I-IV Location Decrease in trials with sites in the US Increase in trials with only non-US sites

Trends in Data 2007-2011 Enrollment remained fairly constant over time within trial phase NIH supported studies have larger median enrollment compared to studies funded by industry or other sources (although NIH supports a smaller number of studies overall) Trial Arms Two arm trials predominate (>6000 registered per year) Large portion of the clinical trials portfolio consists of single arm trials (~4000 registered per year) most common in phase 1-2, but are also reported to be used in phases 2/3, 3, and 4 and in trials where phase is not applicable

Funding Disclosure Financial support for this work was provided by grant U19FD003800 from the U.S. Food and Drug Administration awarded to Duke University for the Clinical Trials Transformation Initiative