ACRIN6664: The National CT Colonography Trial

• Sponsor: American College of Radiology Imaging Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00084929
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2,600
• Locations: 14
• Arm: 1
• Duration (Months): 63.3
• Patients Per Site: 185.7
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

RATIONALE: New diagnostic procedures such as computed tomographic colonography may improve the ability to detect colorectal cancer and may provide a less invasive method of detection.

PURPOSE: This clinical trial is studying how well computed tomographic colonography works in screening healthy participants for colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Procedure: CT Colonography	N/A

Detailed Description

OBJECTIVES:

Primary

• Compare the sensitivity of computed tomographic colonography (CTC) vs colonoscopy for detecting significantly large lesions (≥ 10 mm in diameter) in asymptomatic participants, in terms of specificity, area under the ROC curve, and predictive values for detecting clinically significant colorectal neoplasia.

Secondary

• Determine the interobserver variation in accuracy of interpreting CTC examinations of these participants, including any benefits of a primary 3-dimensional read and/or independent second interpretations.

• Determine the effects of different colon preparations on the accuracy of CTC in these participants.

• Compare participant acceptance and willingness to have a repeat examination by CTC vs colonoscopy.

• Determine the accuracy of CTC in detecting flat lesions in the colon of these participants.

OUTLINE: This is a multicenter study.

Participants receive an oral laxative, oral bisacodyl, and three doses of oral barium sulphate 24 hours before imaging. After cathartic cleansing, participants undergo computed tomographic colonography followed by colonoscopy.

Participants are followed up for approximately 4 weeks.

PROJECTED ACCRUAL: A total of 2,607 participants will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2600 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: The National CT Colonography Trial: Multicenter Assessment of Accuracy for Detection of Large Adenomas and Cancers in a Healthy Screening Population
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Sep 11, 2007
• Actual Study Completion Date: May 13, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CT Colonography CT colonography conducted during the same assessment as colonoscopy.	Procedure: CT Colonography; CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.; Other Names: CT colonography trial colonoscopy

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Advanced Adenomas (>=10mm) as Determined by Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=10mm (as measured at pathology) RS-: No Advanced adenomas >=10mm found by colonoscopy (as measured at pathology)

2. Number of Participants With Advanced Adenomas (>=9mm) Detected by CT Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=9mm (as measured at pathology) RS-: No Advanced adenomas >=9mm found by colonoscopy (as measured at pathology)

3. Number of Participants With Advanced Adenomas (>=8mm) Detected by CT Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=8mm (as measured at pathology) RS-: No Advanced adenomas >=8mm found by colonoscopy (as measured at pathology)

4. Number of Participants With Advanced Adenomas (>=7mm) Detected by CT Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=7mm (as measured at pathology) RS-: No Advanced adenomas >=7mm found by colonoscopy (as measured at pathology)

5. Number of Participants With Advanced Adenomas (>=6mm) Detected by CT Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=6mm (as measured at pathology) RS-: No Advanced adenomas >=16mm found by colonoscopy (as measured at pathology)

6. Number of Participants With Advanced Adenomas (>=5mm) Detected by CT Colonoscopy (Per Patient) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=5mm (as measured at pathology) RS-: No Advanced adenomas >=5mm found by colonoscopy (as measured at pathology)

Secondary Outcome Measures

1. Number of Advanced Adenoma or Cancer Lesions (>=10mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

2. Number of Advanced Adenoma or Cancer Lesions (>=9mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

3. Number of Advanced Adenoma or Cancer Lesions (>=8mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

4. Number of Advanced Adenoma or Cancer Lesions (>=7mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

5. Number of Advanced Adenoma or Cancer Lesions (>=6mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

6. Number of Advanced Adenoma or Cancer Lesions (>=5mm) Detected by CT Colonoscopy (Per Lesion) [within 30 days]

   Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"

7. Interobserver Sensitivity Variability [at baseline]

   Evaluate interobserver variability in Sensitivity (P(T+|D+)) and 95% CI) when interpreting CTC examinations Each study was randomly assigned to be read independently using either a primary 2D search method (conventional 2D image display with 3D endoluminal problem solving), or a primary 3D search method (including the capability of displaying multiplanar 2D) and without prior knowledge of the colonoscopy results. A second trained radiologist of similar skill was assigned to read the images using the other modality Readers were then classified as high performing or not high performing

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

1. Inclusion Criteria

• Male or female outpatients

• Aged 50 years or older

• Scheduled for screening colonoscopy

• Participant's signed informed consent

1. Exclusion Criteria

• Symptoms of disease of the lower gastrointestinal tract, including

• Melanotic stools or/and hematochezia on more than one occasion in the previous six months

• Lower abdominal pain that would normally require a medical evaluation

• Inflammatory bowel disease and/or familial polyposis syndrome

• Serious medical conditions that would increase the risk associated with colonoscopy or are so severe that screening would have no benefit

• Pregnancy

• Previous colonoscopy within the past five years

• Anemia (hemoglobin less than 10 gm/dl)

• Positive fecal occult blood test (FOBT)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
3	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
4	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
5	Invision/Radiology Imaging Associates - Englewood	Englewood	Colorado	United States	80112
6	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
7	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
8	Clinical Radiologists, S.C. at Memorial Medical Center	Springfield	Illinois	United States	62781
9	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
11	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
12	Mallinckrodt Institute of Radiology at Washington University Medical Center	Saint Louis	Missouri	United States	63110
13	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
14	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037

Sponsors and Collaborators

• American College of Radiology Imaging Network
• National Cancer Institute (NCI)

Investigators

• Study Chair: C. Daniel Johnson, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

• Vanness DJ, Knudsen AB, Lansdorp-Vogelaar I, Rutter CM, Gareen IF, Herman BA, Kuntz KM, Zauber AG, van Ballegooijen M, Feuer EJ, Chen MH, Johnson CD. Comparative economic evaluation of data from the ACRIN National CT Colonography Trial with three cancer intervention and surveillance modeling network microsimulations. Radiology. 2011 Nov;261(2):487-98. doi: 10.1148/radiol.11102411. Epub 2011 Aug 3.

• Responsible Party: American College of Radiology Imaging Network
• ClinicalTrials.gov Identifier: NCT00084929
• Other Study ID Numbers: CDR0000367101; ACRIN-6664; U01CA079778; U01CA080098
• First Posted: Jun 11, 2004
• Last Update Posted: Dec 22, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by American College of Radiology Imaging Network: colon cancer; rectal cancer
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Recruitment Details	2600 asymptomatic, out-patients, 50 years or older and prescheduled for screening colonoscopy were recruited for CTC between February 2005 and December 2006.
Pre-assignment Detail	Of the 2607 registration events, 7 were registration errors [duplicate registrations due to system errors] and were cancelled. Therefore, a total of 2600 unique participants were enrolled to the study.

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Period Title: Overall Study
STARTED	2600
COMPLETED	2531
NOT COMPLETED	69

Baseline Characteristics

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Overall Participants	2531
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (7.0)
Sex: Female, Male (Count of Participants)
Female	1326 52.4%
Male	1205 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	97 3.8%
Not Hispanic or Latino	2430 96%
Unknown or Not Reported	4 0.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	10 0.4%
Asian	54 2.1%
Native Hawaiian or Other Pacific Islander	3 0.1%
Black or African American	325 12.8%
White	2075 82%
More than one race	20 0.8%
Unknown or Not Reported	44 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=10mm) as Determined by Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=10mm (as measured at pathology) RS-: No Advanced adenomas >=10mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+	109 4.3%
RS-	2422 95.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis Receiver-operating-characteristic (ROC) curves were estimated with the use of data pooled from the radiologists because of the small number of positive cases reviewed by each radiologist.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.853 to 0.933
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity, for each radiologist, was calculated as the percentage of patients with lesions that were larger than or equal to the prespecified threshold and that were detected on both colonoscopy and CT colonography. The per-patient sensitivity, specificity, positive predictive value, and negative predictive value were first estimated for each radiologist, and then the average values among the radiologists were calculated.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.838 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% confidence intervals were calculated for each radiologist, and large-sample 95% confidence intervals were calculated for overall estimates, with the use of standard errors that allowed for estimation of variation among radiologists.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity, for each radiologist, was calculated as the percentage of patients who did not have lesions larger than the prespecified threshold on colonoscopy as well as CT colonography The per-patient sensitivity, specificity, positive predictive value, and negative predictive value were first estimated for each radiologist, and then the average values among the radiologists were calculated.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.813 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% confidence intervals were calculated for each radiologist, and large-sample 95% confidence intervals were calculated for overall estimates, with the use of standard errors that allowed for estimation of variation among radiologists.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV) the positive predictive value was calculated as the percentage of patients with CT colonographic findings that were also seen on colonoscopy
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; 0.194 to 0.273
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% confidence intervals were calculated for each radiologist, and large-sample 95% confidence intervals were calculated for overall estimates, with the use of standard errors that allowed for estimation of variation among radiologists.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV) the negative predictive value was calculated as the percentage of patients with no CT colonographic findings larger than the prespecified threshold that were not detected on colonoscopy.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.990 to 0.998
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% confidence intervals were calculated for each radiologist, and large-sample 95% confidence intervals were calculated for overall estimates, with the use of standard errors that allowed for estimation of variation among radiologists.

2. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=9mm) Detected by CT Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=9mm (as measured at pathology) RS-: No Advanced adenomas >=9mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+: Advanced Adenoma >=9mm	120 4.7%
RS-: Not Advanced Adenoma >=9mm	2411 95.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.853 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.832 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sensitivity indicates the percent of patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.817 to 0.902
	Parameter Dispersion	Type: Value:
	Estimation Comments	Specificity indicates the percent of patients who had not lesions detected on optical colonoscopy, who had no lesions detected on CTC.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV) CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; 0.209 to 0.292
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV) CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.990 to 0.998
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=8mm) Detected by CT Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=8mm (as measured at pathology) RS-: No Advanced adenomas >=8mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+: Advanced Adenoma >=8mm	154 6.1%
RS-: Not Advanced Adenoma >=8mm	2377 93.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.842 to 0.913
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.803 to 0.929
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sensitivity indicates the percent of patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.825 to 0.909
	Parameter Dispersion	Type: Value:
	Estimation Comments	Specificity indicates the percent of patients who had not lesions detected on optical colonoscopy, who had no lesions detected on CTC.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; 0.256 to 0.355
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.984 to 0.994
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=7mm) Detected by CT Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=7mm (as measured at pathology) RS-: No Advanced adenomas >=7mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+: Advanced Adenoma >=7mm	174 6.9%
RS-: Not Advanced Adenoma >=7mm	2357 93.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.833 to 0.902
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.776 to 0.912
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sensitivity indicates the percent of patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.831 to 0.914
	Parameter Dispersion	Type: Value:
	Estimation Comments	Specificity indicates the percent of patients who had not lesions detected on optical colonoscopy, who had no lesions detected on CTC.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.299 to 0.397
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.980 to 0.992
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=6mm) Detected by CT Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=6mm (as measured at pathology) RS-: No Advanced adenomas >=16mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+: Advanced Adenoma >=6mm	210 8.3%
RS-: Not Advanced Adenoma >=6mm	2321 91.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.810 to 0.878
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.711 to 0.849
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sensitivity indicates the percent of patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.840 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Specificity indicates the percent of patients who had not lesions detected on optical colonoscopy, who had no lesions detected on CTC.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; 0.335 to 0.463
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.971 to 0.984
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Number of Participants With Advanced Adenomas (>=5mm) Detected by CT Colonoscopy (Per Patient)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard (RS) for determining the existence of advanced adenomas. RS+: Colonoscopy found at least 1 Advanced adenomas >=5mm (as measured at pathology) RS-: No Advanced adenomas >=5mm found by colonoscopy (as measured at pathology)
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
RS+: Advanced Adenoma >=5mm	282 11.1%
RS-: Not Advanced Adenoma >=5mm	2249 88.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Accuracy: ROC analysis
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Area Under the Curve (AUC)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.763 to 0.828
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.579 to 0.727
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sensitivity indicates the percent of patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Specificity
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(T-|D-)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.851 to 0.923
	Parameter Dispersion	Type: Value:
	Estimation Comments	Specificity indicates the percent of patients who had not lesions detected on optical colonoscopy, who had no lesions detected on CTC.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Positive Predictive Value (PPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D+|T+)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.389 to 0.513
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Negative Predictive Value (NPV)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	P(D-|T-)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.941 to 0.965
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=10mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	128
Detected by CTC	108
Not Detected	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion (>=10mm))
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.84
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.043
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

8. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=9mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	143
Detected by CTC	117
Not Detected	26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion (>=9mm))
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.82
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.042
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

9. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=8mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	187
Detected by CTC	149
Not Detected	38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion >=8mm)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

10. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=7mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	220
Detected by CTC	165
Not Detected	55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion >=7mm)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.75
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.042
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

11. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=6mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	270
Detected by CTC	189
Not Detected	81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion >=6mm)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.7
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.046
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

12. Secondary Outcome

Title	Number of Advanced Adenoma or Cancer Lesions (>=5mm) Detected by CT Colonoscopy (Per Lesion)
Description	Pathology results from Colonoscopy performed up to 30 days after a CTC examination were used as the reference standard for determining the existence of advanced adenomas. CTC lesions needed to be within 2 segments and 50% size of the lesions removed via colonoscopy to be considered "detected"
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CT Colonography (Per Lesion)
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.
Measure Participants	2531
Measure lesions	374
Detected by CTC	221
Not Detected	153

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT Colonography
	Comments	Sensitivity (per lesion >=5mm)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity: P(T+|D+)
	Estimated Value	0.59
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.045
	Estimation Comments	Sensitivity indicates the percent of lesions in patients who had a lesions (of the specified size) detected by optical colonoscopy, which were detected by CTC

13. Secondary Outcome

Title	Interobserver Sensitivity Variability
Description	Evaluate interobserver variability in Sensitivity (P(T+|D+)) and 95% CI) when interpreting CTC examinations Each study was randomly assigned to be read independently using either a primary 2D search method (conventional 2D image display with 3D endoluminal problem solving), or a primary 3D search method (including the capability of displaying multiplanar 2D) and without prior knowledge of the colonoscopy results. A second trained radiologist of similar skill was assigned to read the images using the other modality Readers were then classified as high performing or not high performing
Time Frame	at baseline

Outcome Measure Data

Analysis Population Description

15 readers read the 2531 case and their sensitivity was calculated as well as the variability (95% CI) in Sensitivity within 2 reader groups: High performing (HP) and not high performing (NHP). HP readers had both a sensitivity and specificity of > 85% for detecting polyps 10 mm and larger, NHP did not.

Arm/Group Title	High Performance (HP) Readers	Non-high Performance (NHP) Readers
Arm/Group Description	Readers were divided into two groups: HP readers had both a sensitivity and specificity of > 85% for detecting polyps 10 mm and larger while NHP readers had a sensitivity and/or specificity < 85%.	NHP readers had a sensitivity and/or specificity < 85%.
Measure Participants	2531	2531
Measure Readers	8	7
Mean (95% Confidence Interval) [probability of (test+ given disease+)]	0.94	0.88

Adverse Events

Time Frame	The adverse event reporting period for this protocol is defined as the period from the initiation of the Computed Tomography Colonography (CTC) procedure and self-reported events were collected for 30 days after the last primary intervention. All participants were monitored for 30days.
Adverse Event Reporting Description	Grade 3 Expected and Unexpected AEs with attribution of possible, probable, or definite - Routine Grade 4 Expected AEs with attribution of possible, probable, or definite - Routine Grade 4 Unexpected AEs with attribution of possible, probable, or definite Expedited Report. Grade 5 AEs, or Deaths with attribution of possible, probable, or definite Telephone Report and Expedited Report
Arm/Group Title	CT Colonography		Colonoscopy
Arm/Group Description	CT colonography conducted during the same assessment as colonoscopy. CT Colonography: CT colonography performed for comparison with colonoscopy results performed during the same screening assessment.		Colonoscopy conducted during the same assessment as CT colonography
All Cause Mortality
	CT Colonography		Colonoscopy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2600 (0%)		0/2600 (0%)
Serious Adverse Events
	CT Colonography		Colonoscopy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2600 (0%)		1/2600 (0%)
Gastrointestinal disorders
hemorrhage with surgery	0/2600 (0%)	0	1/2600 (0%)	1
Other (Not Including Serious) Adverse Events
	CT Colonography		Colonoscopy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2600 (0%)		0/2600 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.