Replacing the Guaiac Fecal Occult Blood Test With the Fecal Immunochemical Test Increases Proportion of Individuals Screened in a Large Healthcare Setting.

BACKGROUND & AIMS: The most commonly used noninvasive test for colorectal cancer (CRC) screening has been the guaiac fecal occult blood test (gFOBT). The fecal immunochemical test (FIT) detects CRC and colorectal polyps with higher levels of sensitivity than the gFOBT, and may be more acceptable to patients. However, the FIT has not replaced the gFOBT in many clinical settings. We analyzed data from a large healthcare system that replaced the gFOBT with the FIT to determine the effects on CRC screening. METHODS: We conducted a retrospective observational study of 7898 patients at the Veterans' Administration San Diego Healthcare System, 50-75 years old, who were offered stool-based CRC screening as part of primary care March 2014 through January 2015. Test orders and results were extracted from electronic health records; we performed manual reviews of colonoscopy and pathology reports for Veterans with positive results from the tests. Our primary outcome was test completion within 1 year of order; secondary outcomes were positive results and detection of advanced neoplasia by diagnostic colonoscopy. The primary analysis used an intention-to-screen approach, which included all patients with test orders; as-screened analyses were also performed. RESULTS: Among 7898 patients, 3236 had gFOBT and 4662 FIT orders. In the intention to screen analysis, a significantly higher proportion of subjects completed a FIT (42.6%) than a gFOBT (33.4%) (P < .001); advanced neoplasia was detected in a significantly higher proportion of subjects offered a FIT (0.79%) than a gFOBT (0.28%) (P = .003). The numbers needed to invite to achieve 1 additional completed test and identify 1 additional patient with advanced neoplasia were 11 and 196, respectively. CONCLUSIONS: In a retrospective study of patients at a Veterans' administration healthcare system, replacing the gFOBT with the FIT increased the proportion of patients who completed CRC screening. Replacement of the gFOBT with the FIT should be strongly considered by all healthcare systems.

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design.

RATIONALE: Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests' comparative effectiveness. STUDY DESIGN: The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs. the annual fecal immunochemical test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening colonoscopy will be superior to a FIT-based screening program in the prevention of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical centers. Participants are randomized to either colonoscopy or annual FIT. Results of colonoscopy are managed as per usual care and study participants are assessed for complications. Participants testing FIT positive are referred for colonoscopy. Participants are surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC mortality. The secondary endpoints are (1) CRC incidence (2) complications of screening colonoscopy, and (3) the association between colonoscopists' characteristics and neoplasia detection, complications and post-colonoscopy CRC. CONFIRM leverages several key characteristics of the VA's integrated healthcare system, including a shared medical record with national databases, electronic CRC screening reminders, and a robust national research infrastructure with experience in conducting large-scale clinical trials. When completed, CONFIRM will be the largest intervention trial conducted within the VA (ClinicalTrials.gov identifier: NCT01239082).

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer.

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach.

Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know.

Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in many jurisdictions, in part because of poor sensitivity for advanced colorectal neoplasms (advanced adenomas and CRC). In order to address this issue, high sensitivity gFOBT have been recommended, however, these tests are limited by a reduction in specificity compared with the traditional gFOBT. Where colonoscopy is available, some providers have opted to recommend screening colonoscopy to their patients instead of faecal testing, as they believe it to be a better test. Newer methods for detecting occult human blood in faeces have been developed. These tests, called faecal immunochemical tests (FIT), are immunoassays specific for human haemoglobin. FIT hold considerable promise over the traditional guaiac methods including improved analytical and clinical sensitivity for CRC, better detection of advanced adenomas, and greater screenee participation. In addition, the quantitative FIT are more flexible than gFOBT as a numerical result is reported, allowing customisation of the positivity threshold. When compared with endoscopy, FIT are less sensitive for the detection of advanced colorectal neoplasms when only one time testing is applied to a screening population; however, this is offset by improved participation in a programme of annual or biennial screens and a better safety profile. This review will describe how gFOBT and FIT work and will present the evidence that supports the use of FIT over gFOBT, including the cost-effectiveness of FIT relative to gFOBT. Finally, specific issues related to FIT implementation will be discussed, particularly with respect to organised CRC screening programmes.

Advances in Fecal Occult Blood Tests: the FIT revolution.

UNLABELLED: There is a wide choice of fecal occult blood tests (FOBTs) for colorectal cancer screening. GOAL: To highlight the issues applicable when choosing a FOBT, in particular which FOBT is best suited to the range of screening scenarios. Four scenarios characterize the constraints and expectations of screening programs: (1) limited colonoscopy resource with a need to constrain test positivity rate; (2) a priority for maximum colorectal neoplasia detection with little need to constrain colonoscopy workload; (3) an "adequate" endoscopy resource that allows balancing the benefits of detection with the burden of service provision; and (4) a need to maximize participation in screening. Guaiac-based FOBTs (gFOBTs) have significant deficiencies, and fecal immunochemical tests (FITs) for hemoglobin have emerged as better tests. gFOBTs are not sensitive to small bleeds, specificity can be affected by diet or drugs, participant acceptance can be low, laboratory quality control opportunities are limited, and they have a fixed hemoglobin concentration cutoff determining positivity. FITs are analytically more specific, capable of quantitation and hence provide flexibility to adjust cutoff concentration for positivity and the balance between sensitivity and specificity. FITs are clinically more sensitive for cancers and advanced adenomas, and because they are easier to use, acceptance rates are high. CONCLUSIONS: FOBT must be chosen carefully to meet the needs of the applicable screening scenario. Quantitative FIT can be adjusted to suit Scenarios 1, 2 and 3, and for each, they are the test of choice. FITs are superior to gFOBT for Scenario 4 and gFOBT is only suitable for Scenario 1.

Racial and ethnic differences in health care utilization and outcomes among ulcerative colitis patients in an integrated health-care organization.

BACKGROUND: Current knowledge of racial disparities in healthcare utilization and disease outcomes for ulcerative colitis (UC) is limited. We sought to investigate these differences among Caucasian, African American, Asian, and Hispanic patients with ulcerative colitis in Kaiser Permanente, a large integrated health-care system in Northern California. METHODS: This retrospective cohort study used computerized clinical data from 5,196 Caucasians, 387 African-Americans, 550 Asians, and 801 Hispanics with prevalent UC identified between 1996 and 2007. Healthcare utilization and outcomes were compared at one and five-year follow-up by use of multivariate logistic regression analysis. RESULTS: Compared with whites, the male-to-female ratio differed for African-Americans (0.68 vs. 0.91, p < 0.01) and Asians (1.3 vs. 0.91, p < 0.01). Asians had fewer co-morbid conditions (p < 0.01) than whites, whereas more African-Americans had hypertension and asthma (p < 0.01). Use of immunomodulators did not differ significantly among race and/or ethnic groups. Among Asians, 5-ASA use was highest (p < 0.05) and the incidence of surgery was lowest (p < 0.01). Prolonged steroid exposure was more common among Hispanics (p < 0.05 at 1-year) who also had more UC-related surgery (p < 0.01 at 5-year) and hospitalization (<0.05 at 5-year), although these differences were not significant in multivariate analysis. CONCLUSIONS: In this population of UC patients with good access to care, overall health-care utilization patterns and clinical outcomes were similar across races and ethnicity. Asians may have milder disease than other races whereas Hispanics had a trend toward more aggressive disease, although the differences we observed were modest. These differences may be related to biological factors or different treatment preferences.

Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010.

BACKGROUND & AIMS: The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently. METHODS: We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult individuals with intact colons using Kaiser Permanente of Northern California's database of members with IBD and general membership data for the period of 1998 to June 2010 (data through 2008 were used to calculate mortality). We also evaluated trends in medication use and rates of cancer detection over time. RESULTS: We identified 29 cancers among persons with Crohn's disease (CD) and 53 among persons with ulcerative colitis (UC). Overall, the incidence rates of cancer among individuals with CD, UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per 100,000 person-years. In the general population, the incidence of CRC was 21% higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the growth of CRC screening programs. The incidence of CRC among individuals with CD or UC was 60% higher than in the general population (95% confidence interval [CI] for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor agents replaced other therapies for CD and UC; the rate of colonoscopy increased by 33% among patients with CD and decreased by 9% in those with UC. CONCLUSIONS: From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than in the general population and essentially stable over time.

Prevalence of colorectal cancer surveillance for ulcerative colitis in an integrated health care delivery system.

BACKGROUND & AIMS: The absence of grade A supporting evidence for surveillance colonoscopy in patients with ulcerative colitis (UC) has led to controversy regarding its benefit, yet it is routinely recommended in practice guidelines. Limited data are available on rates of colonoscopy surveillance and factors associated with surveillance. METHODS: A retrospective study of UC patients receiving care between 2006 and 2007 with ≥ 8 years history of UC was conducted. Primary outcome was the proportion of patients who underwent surveillance during this 2-year study period. Sociodemographic and disease factors were identified a priori from variables recorded electronically in the medical record; multivariable associations with surveillance were estimated using logistic regression. RESULTS: Of 771 patients with ≥ 8 years history of UC, 24.6% of patients underwent at least 1 surveillance colonoscopy within the 2-year study period, with a maximum of 38.5% observed among patients with primary sclerosing cholangitis. In a multivariable analysis, gender, age, race, and education were not associated with surveillance. Factors associated with increasing surveillance included lack of significant comorbidity (Charlson-Deyo index 0 vs 1+: odds ratio [OR], 1.7; 95% confidence interval: 1.1-2.5), > 3 inflammatory bowel disease-related outpatient visits (OR, 2.0; 95% CI: 1.4-3.0), and use of mesalamine (OR, 2.8; 95% CI: 1.7-4.4). CONCLUSIONS: Utilization of surveillance colonoscopy in a 2-year period was low, even among high-risk patients. Although specific factors recorded in computerized data were identified to be associated with surveillance, a greater understanding of how patients and physicians decide on surveillance is needed.

Role of thiopurine and anti-TNF therapy in lymphoma in inflammatory bowel disease.

OBJECTIVES: The objective of this study was to assess inflammatory bowel disease (IBD) medications in relation to lymphoma risk. METHODS: Information on IBD and relevant medications and other utilization was obtained from the Kaiser Permanente IBD Registry, 1996-2009. Lymphoma cases were ascertained from the Kaiser Permanente Cancer Registry. Lymphoma incidence was compared between the IBD cohort and the general Kaiser Permanente population. RESULTS: Of the 16,023 IBD patients without human immunodeficiency virus followed an average 5.8 years, 43 developed lymphoma. IBD patients with and without lymphoma did not differ with respect to past IBD-related visits, procedures, or tests. The standardized incidence rate ratio (SIRR) for lymphoma among IBD patients with no dispensing of thiopurine or anti-tumor necrosis factor (TNF) was 1.0 (95% confidence interval (CI): 0.96-1.1). Of the 21,282 person-years involving exposure to thiopurine or anti-TNF, 81% involved thiopurine alone; 3%, anti-TNF alone; and 16%, combination therapy. Among patients with thiopurine but not anti-TNF dispensings, the SIRR was 0.3 (95% CI: 0.2-0.4) for past use and 1.4 for current use (95% CI: 1.2-2.7). Among patients with dispensing of anti-TNF (with and without thiopurine), the SIRR was 5.5 for past use (95% CI: 4.5-6.6) and 4.4 for current use (95% CI: 3.4-5.4). The most common lymphoma subtypes were diffuse large B-cell lymphoma (44%), follicular lymphoma (14%), and Hodgkin's disease (12%). CONCLUSIONS: Our study provides evidence that IBD alone is not associated with the risk of lymphoma. Use of anti-TNF with thiopurine and current use of thiopurine alone were associated with increased risk, although the effect of disease severity merits further evaluation.

Time trends in therapies and outcomes for adult inflammatory bowel disease, Northern California, 1998-2005.

BACKGROUND & AIMS: The management of inflammatory bowel disease (IBD) has become increasingly complicated, and it is unknown whether poor outcomes (prolonged steroid use, hospitalizations, and surgery) have declined in the general population. METHODS: This multilevel study used computerized clinical data. The study comprised 2892 adults with Crohn's disease (CD) and 5895 with ulcerative colitis (UC) who received care at 16 medical centers within an integrated care organization in Northern California between 1998 and 2005. RESULTS: Time trends included (1) a shift in gastroenterology-related visits from the gastroenterology division to primary care; (2) increased use of IBD-related drugs, except for a 7% decline in use of 5-aminosalicylate in CD and no change in steroid use for CD; (3) for the prevalence of prolonged steroid exposure (120 days of continuous use), a 36% decline for CD with a 27% increase for UC; (4) declines in the hospitalization rates of 33% for CD and 29% for UC; and (5) for the surgery rate, no significant change for CD with a 50% decline for UC. CONCLUSIONS: Declines in prolonged steroid exposure and the hospitalization rate for CD and in the hospitalization and surgery rate for UC are encouraging; however, the increase in prolonged steroid exposure for UC merits concern and further investigation. The variability in care patterns observed in this study suggests lack of standardization of care and the opportunity to identify targets for quality improvement. These findings should stimulate research to quantify the effect of current trends in IBD management.

FIT: a valuable but underutilized screening test for colorectal cancer-it's time for a change.

Although fecal immunochemical tests (FITs) have been used for colorectal cancer (CRC) screening in several countries for years, this has not been the case in the United States. The reasons for this are multifactorial, but if the United States hopes to increase screening rates, the evidence is in regarding FIT's benefits and potential. A publication in this issue of the American Journal of Gastroenterology provides "gold standard" evidence of its superiority over the standard guaiac test and opens opportunities for investigators to discover the most effective uses of this test for population screening.

Incidence, prevalence, and time trends of pediatric inflammatory bowel disease in Northern California, 1996 to 2006.

OBJECTIVE: To examine the incidence and prevalence of pediatric inflammatory bowel disease (IBD) during 1996-2006 in a community-based health-care delivery system. STUDY DESIGN: Members of Kaiser Permanente Northern California aged 0 to 17 years with IBD were identified by use of computerized medical information with confirmation obtained through review of the medical record. RESULTS: The average annual incidence of IBD per 100000 was 2.7 (95% confidence interval [CI], 2.3-3.1) for Crohn's disease (CD) and 3.2 (CI, 2.8-3.6) for ulcerative colitis (UC). During the 11-year study period, the annual incidence per 100000 increased from 2.2 to 4.3 for CD (P = .09) and from 1.8 to 4.9 for UC (P < .001). The ratio of incident CD cases to incident UC cases was 0.9 in non-Hispanic whites, 1.6 in African Americans (P = .12), 0.3 in Hispanics (P < .001) and 0.4 in Asians (P = .04). The average length of enrollment during the 11-year study period exceeded 8 years. The point prevalence on December 31, 2006, per 100000 was 12.0 for CD (CI, 9.6-14.4) and 19.5 (CI, 16.5-22.6) for UC. CONCLUSIONS: In this population the incidence of UC increased significantly by 2.7-fold and CD increased 2.0-fold without reaching statistical significance. Hispanic and Asian children had development of UC more often than CD, suggesting possible etiologic differences across racial and ethnic groups.

Validity of computerized diagnoses, procedures, and drugs for inflammatory bowel disease in a northern California managed care organization.

PURPOSE: Resources for studying inflammatory bowel disease (IBD) are needed in evaluations of drug safety including traditional drugs and new biologics agents. We developed an IBD registry, with ascertainment from computerized visit information. OBJECTIVE: We sought to characterize the positive predictive value (PPV) of IBD case-finding using computerized data compared with chart review. METHODS: We identified 2906 persons aged 89 years or younger with one or more IBD diagnoses in computerized visit data during the period of 1996-2002. The diagnosis of IBD was confirmed through chart review. Adopting chart review as the gold standard, the validity of computerized encounter data to determine IBD was estimated. RESULTS: Among the 2906 study subjects with one or more ICD-9 diagnosis codes of 555 or 556 in computerized data, 81% were confirmed as having IBD by chart review. Defining cases as those who underwent two or more visits without regard to diagnostic procedures or drug utilization maximized the correct classification of cases (PPV, 95%). CONCLUSIONS: The quality of IBD diagnoses in computerized data is adequate to meet the aims of a wide range of research studies.

Stool DNA and occult blood testing for screen detection of colorectal neoplasia.

BACKGROUND: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. OBJECTIVE: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). DESIGN: Blinded, multicenter, cross-sectional study. SETTING: Communities surrounding 22 participating academic and regional health care systems in the United States. PARTICIPANTS: 4482 average-risk adults. MEASUREMENTS: Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. RESULTS: Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). LIMITATIONS: Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. CONCLUSION: Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.

Estimation of the period prevalence of inflammatory bowel disease among nine health plans using computerized diagnoses and outpatient pharmacy dispensings.

BACKGROUND: There are few contemporary estimates of prevalence rates for inflammatory bowel disease (IBD) in diverse North American communities. METHODS: We estimated the period prevalence of IBD for January 1, 1999, through June 30, 2001, among 1.8 million randomly sampled members of nine integrated healthcare organizations in the US using computerized diagnoses and outpatient pharmaceutical dispensing. We also assessed the positive predictive value (PPV) and sensitivities of 1) the case-finding algorithm, and 2) the 30-month sampling period using medical chart review and linkage to a 78-month dataset, respectively. RESULTS: The PPV of the case-finding algorithm was 81% (95% confidence interval [CI], 78-87) and 84% (95% CI, 79-89) in two different organizations. In both, the sensitivity of the optimal algorithm, compared with the most inclusive, exceeded 90%. The sensitivity of the 30-month sampling period compared with 78 months was 61% (95% CI, 57-64) in one organization. Applying a slightly more sensitive case-finding algorithm, the average period prevalence of IBD across the nine organizations, standardized to the age- and gender-distribution of the US population, 2000 census, was 388 cases (95% CI, 378-397) per 100,000 persons (range 209-784 per 100,000; average follow-up 26 months). The prevalence of Crohn's disease, ulcerative colitis, and unspecified IBD was 129, 191, and 69 per 100,000, respectively. CONCLUSIONS: The observed average prevalence was similar to prevalence proportions reported for other North American populations (369-408 per 100,000). Additional research is needed to understand differences in the occurrence of IBD among diverse populations as well as practice variation in diagnosis and treatment of IBD.