Diagnóstico del funcionamiento del Consejo de la Judicatura

El gobierno de la Función Judicial: origen del Consejo de la Judicatura

2.3 Diagnóstico del funcionamiento del Consejo de la Judicatura

• Colorectal cancer (CRC) is one of the most common types of cancers, with over 136,000 new cases identified each year in the United States.1 It typically affects adults over 55 years old, with a median age at diagnosis of 68 years.1

• Screening programs for CRC allow for its early detection. The earlier CRC is caught, the better chance a person has of surviving. Five year survival rates are 89.8% for localized cancer, 70.5% for cancer that has spread regionally, and 12.9% for CRC with distant metastasis.1

• Standard recommended screening for CRC includes fecal occult blood testing, sigmoidoscopy, CT colonography, or colonoscopy. Screening begins at age 50 years (age 45 years for African Americans) and continues until at least age 75 for people at average risk for CRC.2

• Although several screening tests have been endorsed and found to be cost- effective, compliance with CRC screening recommendations is limited. According to 2010 data from the Centers for Disease Control and Prevention (CDC), the percentage of adults over 50 years who reported their CRC screening was up to date ranged from 54.1% to 75.2%, depending on the state. The CDC estimates that 28 million Americans are not up-to-date on CRC screening.3

• The Cologuard screening test (Exact Sciences) is a proprietary multiple

molecular marker assay that measures the presence of certain markers in a stool sample. It is intended to identify people at increased risk for CRC.4 It offers an alternative to current screening options.

Test Information

• Cologuard is performed on a stool sample collected at home and sent to the laboratory for analysis. No bowel preparation or dietary or medication restrictions are required to complete the test.4

• Cologuard analyzes 11 molecular markers, including hemoglobin and DNA markers, in the stool sample. Three categories of markers are targeted for testing:4

o Hypermethylation of the promoter regions of the NDRG4 and BMP3 genes o Point mutations in the KRAS gene

______________________________________________________________________________________________________ © 2016 eviCore healthcare. All Rights Reserved. 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com157 of 486

C

ol

oguar

d

o Hemoglobin assays, which can be associated with the presence of blood in the colon.

• The non-DNA immunochemical assay component used to detect blood is similar to other available Fecal Immunochemical Test (FIT) assays.

• Cologuard provides a single, combined result: positive or negative. People who receive positive results should be referred for a diagnostic colonoscopy. Those with negative results can continue with standard CRC screening

recommendations.4

• Performance characteristics of the Cologuard assay were determined by a large, prospective multicenter trial (DeeP-C Study) and published by Imperiale and colleagues:5

o 9989 participants completed testing and were aged 50-84 years, asymptomatic, and at average risk for CRC. All participants provided a stool sample and underwent diagnostic colonoscopy. The primary outcome was the ability of the Cologuard test to detect CRC. o Sensitivity:

 65 subjects had CRC. 60 of these people had positive Cologuard results, giving a sensitivity of 92.3% foridentifyingcancer [95%CI: 83.0-97.5].

 757 had advanced precancerous lesions. 321 of these people had positive Cologuard results, giving a sensitivity of 42.4% for

identifying precancerous lesions [95%CI: 38.9-46.0].

 Comparable sensitivities of fecal immunochemical testing were 73.8% and 23.8%, respectively, in this trial.

o Specificity:

 9167 subjects had non-advanced adenomas, non-neoplastic findings, and negative results on colonoscopy. 7936 of these

people had negative Cologuard results, giving a specificity of 86.6% [95%CI 85.9-87.2].

 If only those with “true negative” colonoscopies are considered, the specificity was 89.8% [95%CI 88.9-90.7].

 Comparable specificities of fecal immunochemical testing were 94.9% and 96.4%, respectively, in this trial.

Guidelines and Evidence

• Current CRC cancer screening guidelines from the U.S. Preventative Services Task Force (USPSTF, 2008; under revision for 2015) recommend the use of fecal occult blood testing, sigmoidoscopy, and colonoscopy. Fecal DNA tests are not recommended, but the guidelines provide this commentary:4

o “Potential Preventable Burden: Fecal DNA has potential as a highly specific test, and it could reduce harms associated with follow-up of false- positive test results.

o Current Practice: Fecal DNA tests are evolving, and no test is widely used. o Costs: Fecal DNA is likely to have a high monetary cost per test.”

Lab Management Guidelines V1.0.2016

C

ol

oguar

d

• CRC screening guidelines from the National Comprehensive Cancer Network (NCCN, 2014) do not recommend stool DNA testing as a routine screening modality.6 They state: “Emerging technologies such as stool DNA have shown increasing evidence as a reasonably accurate screening modality, but there are limited data to determine an interval between screening. At present, stool DNA is not considered a primary screening modality.”

• The U.S. Food and Drug Administration approved Cologuard in August 2014 as an in vitro diagnostic.7

• A Blue Cross Blue Shield TEC Special Report (2014) reviewed the evidence for Cologuard testing as a CRC screening modality.8 They conclude:

o “The recent study [Imperiale et al, 2014] evaluating a fecal DNA test showed higher sensitivity but lower specificity than FIT. The diagnostic characteristics of the test are consistent with reduced colorectal cancer mortality if used in a longitudinal screening program. However, it remains to be determined how effective the test would be when used at a particular frequency within a screening program, and thus its efficacy and impact on resource use compared with established methods are unknown.”

o “The results of a recent large-scale study of a fecal DNA test (Cologuard) in a screening population have shown that the test has higher sensitivity and lower specificity than FIT, an established screening method. Study quality was good, though the exclusion of some indeterminate fecal DNA test results from the analysis may have biased results slightly. In addition, this study of the diagnostic characteristics of a test for detecting cancer and cancer precursors does not establish efficacy for prevention of colorectal cancer. Effective screening for colorectal cancer requires a program with established screening intervals and appropriate follow-up for positive tests.”

• A prospective, longitudinal study (ClinicalTrials.gov identifier NCT02419716) is currently underway to evaluate the impact of repeat Cologuard testing in an average-risk population at three-year intervals.9

Criteria

• This test is considered investigational and/or experimental.

o Investigational and experimental (I&E) molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene

products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.

o In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory-developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.

C

ol

oguar

d

References

1. SEER Cancer Statistics Factsheets: Colon and Rectum Cancer. National Cancer Institute. Bethesda, MD. Available at http://seer.cancer.gov/statfacts/html/colorect.html.

2. U.S. Preventive Services Task Force. Final Recommendation Statement: Colorectal Cancer: Screening. October 2008. Available at

http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFi nal/colorectal-cancer-screening.

3. Centers for Disease Control and Prevention. Colorectal Cancer. Available at http://www.cdc.gov/cancer/colorectal/index.htm.

4. Cologuard website. Available at http://www.cologuardtest.com.

5. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal- cancer screening. N Engl J Med. 2014 Apr 3;370(14):1287-97. doi:

10.1056/NEJMoa1311194. Epub 2014 Mar 19.

6. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology. Colorectal Cancer Screening. V.1.2014. Available at

http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf.

7. FDA News Release: FDA approves first non-invasive DNA screening test for colorectal cancer. August 11, 2014. Available at

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409021.htm.

8. Blue Cross Blue Shield Association TEC Special Report. Fecal DNA Analysis for Colorectal Cancer Screening. Available at http://www.bcbs.com/blueresources/tec/vols/29/29_8.pdf. 9. ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT02419716.

Lab Management Guidelines V1.0.2016

ConfirmMDx for Prostate Cancer Risk

In document Los modelos de integración del Consejo de la Judicatura y su relación con la independencia del Poder Judicial (página 78-83)