Project description:Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the US, though CRC death can be reduced by screening. However, there is uncertainty as to which screening strategy is most clinically and cost-effective from a population perspective where the aim is to optimize completion of the entire screening process continuum. Modeling studies suggest benefits and harms of colonoscopy and stool blood test strategies are similar, but generally assume 100% participation and subsequent clinically appropriate follow up--something never achieved in clinical practice. Comparative effectiveness studies of testing strategies, including comparisons of specific tests and approaches to optimizing effective test use, are necessary. Safety-net health systems care for populations at increased risk for adverse CRC outcomes, such as the uninsured and minorities, and have more limited resources. Therefore, safety-nets must resolve the uncertainty regarding the most effective screening strategy. The investigators will conduct a system-level, randomized comparative effectiveness trial of the benefits, harms, and costs of 3 screening strategies over 3 years, among 6000 patients age 50-64 years, who are not up-to-date with CRC screening, served by a large safety net health system. The three strategies studied will be: 1) Fecal immunochemical testing, with annual mailed invitation outreach (including a test kit), and a centralized process to promote participation and complete clinical follow up (FIT); 2) Colonoscopy, with annual mailed invitation outreach, and a centralized process to promote participation and complete clinical follow up (Colo); 3) Usual Care, with no mailed invitation outreach, and screening offered at primary care visits. The primary measure of benefit will be an outcome measure that summarizes patient-specific effective screening successes. The primary measure of harm will be screening non-participation. The primary measure of cost will be cost per-patient effectively screened. Our specific aims are to: 1) Compare benefits, harms, and costs of a FIT strategy versus a Colo strategy for CRC screening among patients not up-to-date with screening, and 2) Compare benefits, harms, and costs of a) the FIT strategy vs. Usual Care and b) the Colo strategy vs. Usual Care for CRC screening.

Project description:As part of current harm reduction strategies, candidate modified risk tobacco products (MRTP)s are developed to offer adult smokers who want to continue using tobacco products as an alternative to cigarettes while potentially reducing individual risk and population harm compared to smoking cigarettes. One of these candidate MRTPs is the Tobacco Heating System (THS) 2.2 which does not burn tobacco, but instead heats it, thus producing significantly reduced levels of harmful and potentially harmful constituents (HPHC)s compared with combustible cigarettes (CC). The assessment of MRTPs against combustible cigarettes requires the establishment of exposure-response markers. Biomarkers derived from blood offer for the general population a less invasive alternative than sampling the primary site, such as the airways. Various diseases and exposures, including cigarette smoke, have been shown to alter the molecular profile of the blood. Leveraging this fact, a whole blood derived gene signature that can distinguish current smokers from either non-smokers or former smokers with high specificity and sensitivity was previously reported. Four controlled, parallel randomized groups, open-label clinical studies were conducted with subjects randomized to three groups: (1) switching from CCs to THS2.2 (or its mentholated version, respectively); (2) continuous use of CC; or (3) smoking abstinence. These studies had an investigational period of five days in confinement which was followed by an 85 day ambulatory period for two of them. By measuring biomarkers of exposure to selected HPHCs, these studies showed a consistent reduced exposure in subjects that either stopped smoking or switched to THS2.2 (including mentholated version), compared with subjects who continued smoking their own cigarettes at both day 5 and at day 90. To complement the classical exposure measurements, we tested the small signature consisting of only 11 genes on the blood transcriptome of subjects enrolled in the clinical studies. We show that in all four clinical studies tested, the signature scores were consistently reduced in subjects that either stopped smoking or switched to THS2.2 compared with subjects who continued smoking their conventional tobacco products at both day 6 and at day 91.

Dataset Information

Understanding and Discouraging Overuse of Potentially Harmful Screening Tests

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