|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P130017 / PAS001 |
| Date Original Protocol Accepted |
02/02/2015
|
| Date Current Protocol Accepted |
09/25/2015
|
| Study Name |
Cologuard PAS
|
| Device Name |
COLOGUARD
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The study objective is to collect longitudinal data on subjects for whom Cologuard is used over the course of 3 years. It is a prospective, longitudinal, multi-center study.
|
| Study Population |
The study population is defined with the following criteria: Subjects must meet the following criteria to be eligible for the study:
1. Subject has been prescribed Cologuard for colorectal cancer screening
2. Subject is at average risk for development of colorectal cancer
3. Subject is 50 years or older
4. Subject willing and able to sign informed consent.
5. Subjects not listed in the exclusion criteria, described in 6.2 of the protocol.
|
| Sample Size |
A total of 2,173 subjects will be enrolled to have 1,119 subjects at the year 3 visit (T3) for the Cologuard evaluation assuming
16.1% positivity rate at T0, with 15% annualized lost to follow up (LTFU). Further, it is assumed that 15% of the 1,119 subjects will refuse T3 colonoscopy to result in 951 being evaluable for T3 analyses.
|
| Key Study Endpoints |
The primary endpoint for this study is the difference between the positive predictive value (PPV) at T3 (PPV3) and 1 minus the negative predictive value (NPV) at T3 (NPV3).
The secondary endpoint is the observed vs. the expected reduction in CRC incidence at T3.
Other outcomes to be assessed include the following:
¿The predictive values of a positive Cologuard at T0 and T3 and of a negative Cologuard atT3;
¿The sensitivity and specificity of Cologuard at T3;
¿The positive (PLR) and negative (NLR) likelihood ratios at T3;
¿The cumulative risk of false positive result (cFPR) and cumulative risk of a true positive result
¿(cTPR);
¿The probability that a negative Cologuard result at baseline remains negative through 3 years;
¿The probability that a negative Cologuard result at baseline (T0) results in no CRC/AA through 3 years;
¿The distribution of colorectal epithelial lesions overall and among positive Cologuard subjects at T0 and
¿T3 will be reported with counts and proportions;
¿The rate of adherence to repeat Cologuard at T3 will be reported with counts and proportions;
¿The Cumulative compliance to Colonoscopy following a positive Cologuard result
¿The rate of crossover to alternative screening methodologies (e.g. FOBT, colonoscopy, other) at T1
and T2;
¿The rate of no Cologuard result (e.g. invalid result); and
¿The adverse event rate (events occurring between collection kit distribution and sample submission).
|
| Follow-up Visits and Length of Follow-up |
Study participants will be followed for 3 years
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
2,321
|
| Actual Number of Sites Enrolled |
40
|
| Patient Follow-up Rate |
Of the 2,321 subjects enrolled in the study, T0 Cologuard results were obtained for 2,073 (89.3%), with 284 subjects obtaining a positive result and 1,760 subjects obtaining a negative result. The study design required all subjects with a negative T0 Cologuard result to remain in the study and return for follow-ups. A total of 1,645 of the possible 1,760 eligible subjects (93.5%) completed the T1 office/phone visit, 1,510 (87.1%) subjects completed the T2 office/phone visit, and 1,223 (75.7%) p
|
| Final Safety Findings |
No adverse events were reported.
|
| Final Effect Findings |
The primary endpoint is the Predictive Summary Index (PSI), defined as (PPV3-[1-NPV3]), where PPV3 is the positive predictive value at T3 and NPV3 is the negative predictive value at T3. The primary endpoint was calculated for CRC alone and for CRC+AA combined. A PSI value of 0% reflects a test with no predictive value. No CRCs were detected at T3, the PSI for CRC alone was 0, and the PSI for CRC+AA combined was 9.29% (95% CI 1.83%, 17.63%, p-value = 0.0124).
The secondary endpoint was the observed versus the expected reduction in colorectal cancer (CRC) incidence at T3. Only 1 case of CRC occurred after T0, giving an observed incidence after a negative T0 Cologuard of 0.001374, numerically less than expected (two-sided p=0.0729 or one-sided p = 0.0402.
|
| Study Strengths & Weaknesses |
Weakness: low procedure compliance rate for primary endpoints, only 37.1% patients (653 out of 1760) had colonoscopy at T3, only 33.5% patients (591) had both valid Cologuard and colonoscopy at T3 for study endpoint analyses. No statistical adjustment for multiplicity.
Strength: 3-year long term data
|
| Recommendations for Labeling Changes |
Yes
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