In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
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 Description
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.
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.
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
¿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
¿The rate of no Cologuard result (e.g. invalid result); and
¿The adverse event rate (events occurring between collection kit distribution and sample submission).