Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision.

BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Use of 2-Stage Modeling to Identify How Colorectal Cancer Risk Changes With Period and Cohort.

Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 years or older while increasing in adults under age 50 years. Understanding these trends is challenging because of the multiple related time scales of age, diagnosis period, and birth cohort. We analyzed incidence rates of rectal, distal colon, and proximal colon cancer for individuals aged 20 years or more from the Surveillance, Epidemiology, and End Results Program for diagnosis years 1978-2017. We used a 2-stage generalized linear model to determine age, period, and cohort effects for CRC incidence. We first estimated birth cohort effects among people under age 45 years. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people aged 45 years or more. There was no evidence of period effects for people under age 45 years. Risks of rectal and distal colon cancer increased for later birth cohorts. Compared with the 1943-1952 birth cohort, the 1983-1992 birth cohort had 2.2 times the risk of rectal cancer, 1.9 times the risk of distal colon cancer, and 1.3 times the risk of proximal colon cancer. For people aged ≥45 years, period effects showed declines in CRC risk that were attributable to screening.

Sequentially calibrating a Bayesian microsimulation model to incorporate new information and assumptions.

BACKGROUND: Microsimulation models are mathematical models that simulate event histories for individual members of a population. They are useful for policy decisions because they simulate a large number of individuals from an idealized population, with features that change over time, and the resulting event histories can be summarized to describe key population-level outcomes. Model calibration is the process of incorporating evidence into the model. Calibrated models can be used to make predictions about population trends in disease outcomes and effectiveness of interventions, but calibration can be challenging and computationally expensive. METHODS: This paper develops a technique for sequentially updating models to take full advantage of earlier calibration results, to ultimately speed up the calibration process. A Bayesian approach to calibration is used because it combines different sources of evidence and enables uncertainty quantification which is appealing for decision-making. We develop this method in order to re-calibrate a microsimulation model for the natural history of colorectal cancer to include new targets that better inform the time from initiation of preclinical cancer to presentation with clinical cancer (sojourn time), because model exploration and validation revealed that more information was needed on sojourn time, and that the predicted percentage of patients with cancers detected via colonoscopy screening was too low. RESULTS: The sequential approach to calibration was more efficient than recalibrating the model from scratch. Incorporating new information on the percentage of patients with cancers detected upon screening changed the estimated sojourn time parameters significantly, increasing the estimated mean sojourn time for cancers in the colon and rectum, providing results with more validity. CONCLUSIONS: A sequential approach to recalibration can be used to efficiently recalibrate a microsimulation model when new information becomes available that requires the original targets to be supplemented with additional targets.

Making Narrative Statements to Describe Treatment Effects.

Accurately describing treatment effects using plain language and narrative statements is a critical step in communicating research findings to end users. However, the process of developing these narratives has not been historically guided by a specific framework. The Agency for Healthcare Research and Quality Evidence-based Practice Center Program developed guidance for narrative summaries of treatment effects that identifies five constructs. We explicitly identify these constructs to facilitate developing narrative statements: (1) direction of effect, (2) size of effect, (3) clinical importance, (4) statistical significance, and (5) strength or certainty of evidence. These constructs clearly overlap. It may not always be feasible to address all five constructs. Based on context and intended audience, investigators can determine which constructs will be most important to address in narrative statements.

Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations. Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer. Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies. Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

The Relationship Between Engagement in Online Support Groups and Social Isolation Among Military Caregivers: Longitudinal Questionnaire Study.

BACKGROUND: There is a lack of research on the effectiveness of online peer support groups for reducing social isolation and depressive symptoms among caregivers, and previous research has mixed results. OBJECTIVE: This study aimed to test whether military caregivers who joined a new online peer support community or engaged with an existing online community experienced decreased perceived social isolation and improved depressive symptoms over 6 months. METHODS: We conducted a longitudinal study of 212 military caregivers who had newly joined an online community and those who were members of other military caregiver groups. Multiple indicators of perceived social isolation and depressive symptoms were assessed at baseline and at 3 and 6 months. RESULTS: Compared with caregivers in the comparison group, caregivers who joined the new group experienced less perceived social isolation at 3 months (eg, number of caregivers in social network [unstandardized regression coefficients] b=0.49, SE 0.19, 95% CI 0.87 to 0.02), but this effect did not persist at 6 months. Those who engaged more with new or existing groups experienced less perceived social isolation over time (eg, number of caregivers in social network b=0.18, SE 0.06, 95% CI 0.02 to 0.27), and this relationship was mediated by increased interactions with other military caregivers (95% CI 0.0046 to 0.0961). Engagement with an online group was not associated with improvements in depressive symptoms. CONCLUSIONS: Online communities might help reduce social isolation when members engage with the group, but more intensive treatment is needed to improve depressive symptoms.

Are Publicly Funded Health Databases Geographically Detailed and Timely Enough to Support Patient-Centered Outcomes Research?

Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.

Improving pragmatic clinical trial design using real-world data.

BACKGROUND: Pragmatic clinical trials often use automated data sources such as electronic health records, claims, or registries to identify eligible individuals and collect outcome information. A specific advantage that this automated data collection often yields is having data on potential participants when design decisions are being made. We outline how this data can be used to inform trial design. METHODS: Our work is motivated by a pragmatic clinical trial evaluating the impact of suicide-prevention outreach interventions on fatal and non-fatal suicide attempts in the 18 months after randomization. We illustrate our recommended approaches for designing pragmatic clinical trials using historical data from the health systems participating in this study. Specifically, we illustrate how electronic health record data can be used to inform the selection of trial eligibility requirements, to estimate the distribution of participant characteristics over the course of the trial, and to conduct power and sample size calculations. RESULTS: Data from 122,873 people with patient health questionnaire (PHQ) responses, recorded in their electronic health records between 1 July 2010 and 31 March 2012, were used to show that the suicide attempt rate in the 18 months following completion of the questionnaire varies by response to item nine of the PHQ. We estimated that the proportion of individuals with a prior recorded elevated PHQ (i.e. history of suicidal ideation) would decrease from approximately 50% at the beginning of a trial to about 5%, 50 weeks later. Using electronic health record data, we conducted simulations to estimate the power to detect a 25% reduction in suicide attempts. Simulation-based power calculations estimated that randomizing 8000 participants per randomization arm would allow 90% power to detect a 25% reduction in the suicide attempt rate in the intervention arm compared to usual care at an alpha rate of 0.05. CONCLUSIONS: Historical data can be used to inform the design of pragmatic clinical trials, a strength of trials that use automated data collection for randomizing participants and assessing outcomes. In particular, realistic sample size calculations can be conducted using real-world data from the health systems in which the trial will be conducted. Data-informed trial design should yield more realistic estimates of statistical power and maximize efficiency of trial recruitment.

Characteristics of Chiropractic Patients Being Treated for Chronic Low Back and Neck Pain.

OBJECTIVES: Chronic low back pain (CLBP) and chronic neck pain (CNP) are the most common types of chronic pain, and chiropractic spinal manipulation is a common nonpharmacologic treatment. This study presents the characteristics of a large United States sample of chiropractic patients with CLBP and CNP. METHODS: Data were collected from chiropractic patients using multistage systematic stratified sampling with 4 sampling levels: regions and states, sites (ie, metropolitan areas), providers and clinics, and patients. The sites and regions were San Diego, California; Tampa, Florida; Minneapolis, Minnesota; Seneca Falls and Upstate New York; Portland, Oregon; and Dallas, Texas. Data were collected from patients through an iPad-based prescreening questionnaire in the clinic and emailed links to full screening and baseline online questionnaires. The goal was 20 providers or clinics and 7 patients with CLBP and 7 with CNP from each clinic. RESULTS: We had 6342 patients at 125 clinics complete the prescreening questionnaire, 3333 patients start the full screening questionnaire, and 2024 eligible patients completed the baseline questionnaire: 518 with CLBP only, 347 with CNP only, and 1159 with both. In general, most of this sample were highly-educated, non-Hispanic, white females with at least partial insurance coverage for chiropractic care who have been in pain and using chiropractic care for years. Over 90% reported high satisfaction with their care, few used narcotics, and avoiding surgery was the most important reason they chose chiropractic care. CONCLUSIONS: Given the prevalence of CLBP and CNP, the need to find effective nonpharmacologic alternatives for chronic pain, and the satisfaction these patients found with their care, further study of these patients is worthwhile.

Risks Associated With Anesthesia Services During Colonoscopy.

BACKGROUND & AIMS: We aimed to quantify the difference in complications from colonoscopy with vs without anesthesia services. METHODS: We conducted a prospective cohort study and analyzed administrative claims data from Truven Health Analytics MarketScan Research Databases from 2008 through 2011. We identified 3,168,228 colonoscopy procedures in men and women, aged 40-64 years old. Colonoscopy complications were measured within 30 days, including colonic (ie, perforation, hemorrhage, abdominal pain), anesthesia-associated (ie, pneumonia, infection, complications secondary to anesthesia), and cardiopulmonary outcomes (ie, hypotension, myocardial infarction, stroke), adjusted for age, sex, polypectomy status, Charlson comorbidity score, region, and calendar year. RESULTS: Nationwide, 34.4% of colonoscopies were conducted with anesthesia services. Rates of use varied significantly by region (53% in the Northeast vs 8% in the West; P < .0001). Use of anesthesia service was associated with a 13% increase in the risk of any complication within 30 days (95% confidence interval [CI], 1.12-1.14), and was associated specifically with an increased risk of perforation (odds ratio [OR], 1.07; 95% CI, 1.00-1.15), hemorrhage (OR, 1.28; 95% CI, 1.27-1.30), abdominal pain (OR, 1.07; 95% CI, 1.05-1.08), complications secondary to anesthesia (OR, 1.15; 95% CI, 1.05-1.28), and stroke (OR, 1.04; 95% CI, 1.00-1.08). For most outcomes, there were no differences in risk with anesthesia services by polypectomy status. However, the risk of perforation associated with anesthesia services was increased only in patients with a polypectomy (OR, 1.26; 95% CI, 1.09-1.52). In the Northeast, use of anesthesia services was associated with a 12% increase in risk of any complication; among colonoscopies performed in the West, use of anesthesia services was associated with a 60% increase in risk. CONCLUSIONS: The overall risk of complications after colonoscopy increases when individuals receive anesthesia services. The widespread adoption of anesthesia services with colonoscopy should be considered within the context of all potential risks.

Association Between Primary Care Visits and Colorectal Cancer Screening Outcomes in the Era of Population Health Outreach.

BACKGROUND: Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown. OBJECTIVE: To assess associations between primary care provider (PCP) visits and receipt of CRC screening and colonoscopy after a positive fecal immunochemical (FIT) or fecal occult blood test (FOBT). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 968,072 patients ages 50-74 years who were not up to date with CRC screening in 2011 in four integrated healthcare systems (three with screening outreach programs using FIT kits) in the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. MEASURES: Demographic, clinical, PCP visit, and CRC screening data were obtained from electronic health records and administrative databases. We examined associations between PCP visits in 2011 and receipt of FIT/FOBT, screening colonoscopy, or flexible sigmoidoscopy (CRC screening) in 2012 and follow-up colonoscopy within 3 months of a positive FIT/FOBT in 2012. We used multivariable logistic regression and propensity score models to adjust for confounding. RESULTS: Fifty-eight percent of eligible patients completed a CRC screening test in 2012, most by FIT. Those with a greater number of PCP visits had higher rates of CRC screening at all sites. Patients with ≥1 PCP visit had nearly twice the adjusted-odds of CRC screening (OR = 1.88, 95 % CI: 1.86-1.89). Overall, 79.6 % of patients with a positive FIT/FOBT completed colonoscopy within 3 months. Patients with ≥1 PCP visit had 30 % higher adjusted odds of completing colonoscopy after positive FIT/FOBT (OR = 1.30; 95 % CI: 1.22-1.40). CONCLUSIONS: Patients with a greater number of PCP visits had higher rates of both incident CRC screening and colonoscopy after positive FIT/FOBT, even in health systems with active population health outreach programs. In this era of virtual care and population outreach, primary care visits remain an important mechanism for engaging patients in cancer screening.

Variation in Screening Abnormality Rates and Follow-Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Consortium.

BACKGROUND: Primary care providers and health systems have prominent roles in guiding effective cancer screening. OBJECTIVE: To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. DESIGN: Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. PARTICIPANTS: Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years). INTERVENTION: Breast, colorectal, or cervical cancer screening. MAIN MEASURES: Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up. KEY RESULTS: There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7  % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %). CONCLUSIONS: Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.

Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States. OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC. DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016. STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events. RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings. CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.

IMPORTANCE: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations. OBJECTIVE: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden. DESIGN, SETTING, AND PARTICIPANTS: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis. EXPOSURES: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed. MAIN OUTCOMES AND MEASURES: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds. RESULTS: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG). CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

PURPOSE: Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation. METHODS: We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health. RESULTS: Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40 mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC increase: 0.99, 0.71-1.38). CONCLUSIONS: Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.

Prevalence of colonoscopy before age 50.

OBJECTIVE: Describe the prevalence of colonoscopy before age 50, when guidelines recommend initiation of colorectal cancer screening for average risk individuals. METHOD: We assembled administrative health records that captured receipt of colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old members of four US health plans and used backward recurrence time models to estimate trends in receipt of colonoscopy before age 50 and variation in early colonoscopy by age and sex. We also used self-reported receipt of colonoscopy from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview Survey (NHIS) to estimate the association between early colonoscopy and sex, race/ethnicity, and geographic location based on logistic regression models that accounted for the complex NHIS sampling design. RESULTS: About 5% of the health plan cohort had a record of colonoscopy before age 50. Receipt of early colonoscopy increased significantly from 1999 to 2010 (test for linear trend, p<0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in the east coast health plan compared to west coast and Hawaii plans. The NHIS analysis found that early colonoscopy was more likely in Northeastern residents compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39). CONCLUSION: Colonoscopy before age 50 is increasingly common.