Authors' objectives:

This Assessment will evaluate whether there is sufficient evidence to evaluate the performance of immunochemical fecal occult blood test (iFOBTs) in general, or of specific iFOBTs, and to compare performance to standard guaiac-based FOBTs (gFOBTs). In addition, this Assessment will examine the evidence on patient compliance with various FOBT formats to determine if compliance is more likely with any or with a specific iFOBT versus gFOBTs.

Authors' results and conclusions: Based on the available evidence, the Blue Cross and Blue Shield Medical Advisory Panel made the following judgments about whether immunochemical fecal occult blood tests meet the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate governmental regulatory bodies. InSure(TM)(Enterix, Inc.), Instant-View(R)(Alpha Scientific Designs, Inc.), immoCARE(R)(Care Products, Inc.), FlexSure(R) OBT (Beckman Coulter), HemeSelect(R) (Beckman Coulter), and MonoHaem(R) (Chemicon International, Inc.) are iFOBTs that have received U.S. Food and Drug Administration (FDA) approval. However, FlexSure(R) OBT and HemeSelect(R) assays are no longer available commercially in the U.S. Guaiac-based FOBTs and most iFOBTs are categorized as waived under Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulation and may be developed in any laboratory with a CLIA license for waived tests, such as a physicians office lab. Tests may be waived from regulatory oversight if they meet certain requirements established by the statute. Minimal scientific and technical knowledge, training, and experience are required to perform waived tests. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. Annual or biennial screening with gFOBTs has been shown in large, randomized trials to have a significant and beneficial effect on colorectal cancer incidence and mortality. However, while the specificity of these tests is generally high, sensitivity is poor. Complicated dietary restrictions prior to testing and sampling instructions may limit patient compliance. Newer, immunochemical tests are reported to have improved performance characteristics compared to guaiac tests, no dietary restrictions, and in the case of 1 immunochemical test, InSure, simpler instructions for sampling. By comparing iFOBT performance characteristics and patient compliance to thosefor standard gFOBTs, effects on health outcomes can be inferred. Is there sufficient evidence to evaluate the performance of iFOBTs in general? Are there relative differences in performance among iFOBTs? Is iFOBT performance as good as or better than that of standard gFOBTs? The minimum study inclusion criteria for evaluating iFOBT performance were as follows: - Published as a full-length article in the English language - Enrolled a well-described patient group for CRC screening - Excluded patients with known causes of bleeding - Successfully completed FOBT by at least 85% of enrollees - Performed endoscopy on all enrollees - Compared 2 or more FOBTs including at least 1 iFOBT - Used no rehydration for Hemoccult II tests - Reported FOBT results for cancer, adenomas larger than 1 cm, or both combined Seven studies met these criteria, enrolling a total of 3,000 individuals for gFOBT testing and 3,834 for iFOBT testing. None of the studies enrolled an average-risk colorectal cancer screening population. To compare performance of screening tests, smaller studies of higher-risk screening populations in which all receive endoscopy were considered acceptable to increase the yield of neoplasia while avoiding verification bias. The majority of comparative data on iFOBTs are derived from studies of FlexSure OBT (n=2,946) and HemeSelect (n=1,853), neither of which are currently available in the U.S. Considering only iFOBTs that are FDA approved and currently available in the U.S., only 1 included study evaluated InSure (n=443) and 1 evaluated MonoHaem (n=81); none evaluated Instant-View or immoCARE. However, it is not clear that iFOBTs can be evaluated as an assay class. iFOBTs vary in their detection limit, determined by adding known quantities of fresh, human blood. For example, MonoHaem has the highest detection limit for hemoglobin and, judging from 1 small study (n=81), poor clinical sensitivity compared to Hemoccult II. However, the InSure assay reportedly has a detection limit that is 6 times lower than that of FlexSure but in 1 study (n=443) InSure and FlexSure performed equally. Thus, artificially determined detection limits may not predict comparative clinical performance. Therefore, the evidence on clinical performance of immunochemical FOBTs currently available in the U.S. compared to guaiac FOBTs is limited to 1 study comparing InSure to FlexSure and 1 study comparing MonoHaem to Hemoccult II and is insufficient for drawing conclusions. Does the evidence indicate that compliance is more likely with an iFOBT compared to gFOBT? Is there a specific iFOBT that increases compliance? For evaluation of the effect of iFOBTs on patient compliance, all available studies were included. Only 1 study addressed the effect of sampling method on patient compliance with FOBT testing. In a population randomly chosen from electoral rolls in Australia, not in association with a health care setting, sampling from 2 versus 3 stools and sampling toilet water around a stool with a brush (InSure) versus capturing a dry specimen for sampling with a spatula (Hemoccult SENSA, FlexSure OBT) was associated with significantly increased compliance. Whether or not these factors affect compliance when FOBT testing is recommended in a U.S. health care setting, e.g., by a patients general physician, is not known. The evidence is insufficient to evaluate the effect of sampling method on patient compliance with FOBT testing. Several studies have tested the effect of dietary restrictions versus none for compliance with performing the same FOBT, with conflicting results. Because study settings, populations, and specific dietary restrictions differ across studies, it is not possible to draw conclusions regarding the effect of dietary restrictions on patient compliance with FOBT testing. 3. The technology must improve the net health outcome; and 4. The technology must be as beneficial as any established alternatives. There is insufficient evidence to permit conclusions regarding the use of immunochemical fecal occult blood testing for colorectal cancer screening and health outcomes. 5. The improvement must be attainable outside the investigational settings. Whether or not the use of immunochemical fecal occult blood testing for colorectal cancer screening improves health outcomes has not been demonstrated in the investigational setting.

Authors' recommendations: Based on the above, the use of immunochemical fecal occult blood testing for colorectal cancer screening does not meet the TEC criteria.

Authors' methods: Review

Project Status: Completed

URL for project: http://www.bcbs.com/blueresources/tec/contact-tec.html

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)