From the Journals

Adjusting fecal immunochemical test thresholds improved their performance

 

Key clinical point: To minimize the heterogeneity of fecal immunochemical screening tests, adjust thresholds to produce a predetermined specificity or a manageable rate of positivity.

Major finding: Adjusting detection thresholds to obtain preset specificities (99%, 97%, or 93%) greatly narrowed both sensitivity (14%-18%, 21%-24%, and 30%-35%, respectively) and rates of positivity (2.8%-3.4%, 5.8%-6.1%, and 10%-11%, respectively).

Data source: A comparison of nine different fecal immunochemical assays in 516 patients, of whom 216 had colorectal neoplasias.

Disclosures: Manufacturers provided test kits free of charge. There were no other external sources of support, and the researchers reported having no conflicts of interest.

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Quantitative measurement of fecal hemoglobin: Improving FIT screening

The fecal immunochemical test (FIT) is an important option for colorectal cancer screening, endorsed by guidelines and effective for mass screening using mailed outreach. Patients offered FIT or a choice between FIT and colonoscopy are more likely to be screened.

In the United States, FIT is a qualitative test (reported as positive or negative), based on Food and Drug Administration regulations, in an attempt to simplify clinical decision making. In Europe, FIT has been used quantitatively, with adjustable positivity rate and sensitivity pegged to available colonoscopy resources. Adding complexity, there are multiple FIT brands, each with varying performance, even at similar hemoglobin concentrations. Each brand has a different sensitivity, specificity, and positivity rate, because reagents, buffers, and collection devices vary. Ambient temperature during mailing and transport time to processing labs can also affect test performance.

Dr. Theodore R. Levin
It is appealing for program administrators to adjust hemoglobin cutoffs, managing positivity, specificity, and sensitivity of FIT. Colonoscopy resources are difficult to expand, and a high positivity rate can lead to excess patient and physician anxiety. In the Dutch national colorectal cancer screening program, changing brands between the pilot phase and implementation led to a disruptive increase in test positivity. This strained available colonoscopy resources and led to long backlogs for follow-up colonoscopy. Program stakeholders responded by raising the positivity threshold. In the United States, however, adjustable FIT thresholds are not currently an option for clinical practice. Research such as this will help inform the need for more flexible hemoglobin cutoffs.

Theodore R. Levin, MD, is chief of gastroenterology, Kaiser Permanente Medical Center, Walnut Creek, Calif. He has no conflicts of interest.


 

FROM GASTROENTEROLOGY

Physicians can minimize the heterogeneity of fecal immunochemical colorectal cancer screening tests by adjusting thresholds for positivity, according to researchers. The report is in the January issue of Gastroenterology (doi: 10.1053/j.gastro.2017.09.018).

The investigators directly compared nine different fecal immunochemical assays using stool samples from 516 individuals, of whom 216 had advanced adenoma or colorectal cancer. Using thresholds recommended by manufacturers (2-17 mcg Hb/g feces) produced widely ranging sensitivities (22%-46%) and specificities (86%-98%). Using a uniform threshold of 15 mcg Hb/g feces narrowed the range of specificity (94%-98%), but sensitivities remained quite variable (16%-34%). Adjusting detection thresholds to obtain preset specificities (99%, 97%, or 93%) greatly narrowed both sensitivity (14%-18%, 21%-24%, and 30%-35%, respectively) and rates of positivity (2.8%-3.4%, 5.8%-6.1%, and 10%-11%, respectively), the researchers reported.

Increasingly, physicians are using fecal immunochemical testing to screen for colorectal neoplasia. In a prior study (Ann Intern Med. 2009 Feb 3;150[3]:162-90) investigators evaluated the diagnostic performance of six qualitative point-of-care fecal immunochemical tests among screening colonoscopy patients in Germany, and found that the tests had highly variable sensitivities and specificities for the detection of colorectal neoplasia. Not surprisingly, the most sensitive tests were the least specific, and vice versa, which is the problem with using fixed thresholds in qualitative fecal immunochemical tests, the researchers asserted.

Quantitative fecal immunochemical tests are more flexible than qualitative assays because users can adjust thresholds based on fecal hemoglobin concentrations. However, very few studies had directly compared sensitivities and specificities among quantitative fecal immunochemical tests, and “it is unclear to what extent differences ... reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions,” the investigators wrote. Patients in their study underwent colonoscopies in Germany between 2005 and 2010, and fecal samples were stored at –80 °C until analysis. The researchers calculated test sensitivities and specificities by using colonoscopy and histology reports evaluated by blinded, trained research assistants.

“Apparent heterogeneity in diagnostic performance of quantitative fecal immunochemical tests can be overcome to a large extent by adjusting thresholds to yield defined levels of specificity or positivity rates,” the investigators concluded. Only 16 patients in this study had colorectal cancer, which made it difficult to pinpoint test sensitivity for this finding, they noted. However, they found similar sensitivity estimates for colorectal cancer in an ancillary clinical study.

Manufacturers provided test kits free of charge. There were no external funding sources, and the researchers reported having no conflicts of interest.

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