Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children

Abstract

Background & aims: The level of fecal calprotectin (FC) can predict the onset of inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated the cost-effectiveness of using measurements of FC to identify adults and children who require endoscopic confirmation of IBD.

Methods: We constructed a decision analytic tree to compare the cost-effectiveness of measuring FC before endoscopy examination with that of direct endoscopic evaluation alone. A second decision analytic tree was constructed to evaluate the cost-effectiveness of FC cutoff levels of 100 μg/g vs 50 μg/g (typically used to screen for intestinal inflammation). The primary outcome measure was the incremental cost required to avoid 1 false-negative result by using FC level to diagnose new-onset IBD.

Results: In adults, FC screening saved $417/patient but delayed diagnosis for 2.2/32 patients with IBD among 100 screened patients. In children, FC screening saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100 screened patients. If endoscopic biopsy analysis remained the standard for diagnosis, direct endoscopic evaluation would cost an additional $18,955 in adults and $6250 in children to avoid 1 false-negative result from FC screening. Sensitivity analyses showed that cost-effectiveness of FC screening varied with the sensitivity of the test and the pre-test probability of IBD in adults and children. Pre-test probabilities for IBD of ≤75% in adults and ≤65% in children made FC screening cost-effective, but it was cost-ineffective if the probabilities were ≥85% and ≥78% in adults and children, respectively. Compared with the FC cutoff level of 100 μg/g, the cutoff level of 50 μg/g cost an additional $55 and $43 for adults and children, respectively, but it yielded 2.4 and 6.1 additional accurate diagnoses of IBD per 100 screened adults and children, respectively.

Conclusions: Screening adults and children to measure fecal levels of calprotectin is effective and cost-effective in identifying those with IBD on a per-case basis when the pre-test probability is ≤75% for adults and ≤65% for children. The utility of the test is greater for adults than children. Increasing the FC cutoff level to ≥50 μg/g increases diagnostic accuracy without substantially increasing total cost.

Keywords: CD; Colonoscopy; Cost-effectiveness; Crohn's Disease; Crohn's disease; DEE; Endoscopy; FC; FCS; Fecal Calprotectin; IBD; ICER; Inflammatory Bowel Disease; PSA; QALY; UC; Ulcerative Colitis; WTP; direct endoscopic evaluation; fecal calprotectin; fecal calprotectin screening; incremental cost-effectiveness ratio; inflammatory bowel disease; probabilistic sensitivity analysis; quality-adjusted life year; ulcerative colitis; willingness to pay.

Figure 1. Overview of model structure

* ‘endoscopy’ = upper endoscopy and colonoscopy with histopathology

Figure 2. One-Way Sensitivity Analysis

* varied from -$551 to $15,510 per additional IBD diagnosis; † varied from -$17,722 to $5,907 per additional IBD diagnosis.

Figure 3. Probabilistic Sensitivity Analysis

Acceptability curves from the 3,000 independent simulations. Figure A and B show FCS strategy decreases in cost-effectiveness at higher WTP. Figure C and D show that FCS at low FC cut-off values have a wider range of WTP (between 2 vertical hurdles) in which FCS at 50µg/g is the more likely cost-effective than FCS at 100µg/g (between the left hurdle and the origin).

Figure 4. 3-Way Sensitivity Analysis for Using FC Assay in Pediatric Group

ICER of DEE strategy at different pre-test probabilities of true IBD, as compared with FCS strategy.