THE DIAGNOSTIC ACCURACY AND COST-EFFECTIVENESS OF SEROLOGIC TESTS IN THE DIAGNOSIS OF CELIAC DISEASE

Purpose: To evaluate the diagnostic accuracy and cost-effectiveness of IgA (immunoglobulin A) and IgG serologic tests in the diagnosis of celiac disease including anti-tissue transglutaminase (tTG), anti-deamidated gliadin peptide (DGP), anti-endomysial antibody (EMA), and anti-gliadin (AGA) antibodies.

Method: A systematic literature review was conducted to identify studies published between January 2000 and November 2009 that evaluated the sensitivity and specificity of serologic celiac disease tests using small bowel biopsy as the gold standard. The patient population consisted of untreated subjects with symptoms consistent with the disease. Pooled estimates of sensitivity and specificity were calculated using a bivariate, binomial generalized linear mixed model (SAS 9.2). Statistical significance was defined by p-values  less than 0.05, “false discovery rate” adjustments were made for multiple hypothesis testing. A decision analysis was constructed (TreeAge Pro Suite 2009) to compare costs and outcomes based on the pooled estimates. Costs of serologic tests, endoscopy, small bowel biopsy, and physician fees in Canadian dollars were included. The outcome was expected costs per false negative (FN).

Result: Seventeen eligible studies were identified. The pooled sensitivity for IgA tTG was 92.1% [95% confidence interval (CI) 88.0, 96.3], 89.2% (83.3, 95.1, p=0.12) for IgA DGP, 85.1% (79.5, 94.4, p=0.07) for IgA EMA, 74.9% (63.6, 86.2, p=0.0003) for IgA AGA, and 44.7% (30.3, 59.2, p<0.0003) for IgG tTG. Serologic test combinations slightly increased the sensitivity, 95.1% (92.2, 98.0, p=0.039 vs. IgA tTG). Specificity ranged between 90.1% and 93.9% and was similar among the tests. Small bowel biopsy was assumed to have 100% accuracy since it is the gold standard. IgG tTG was the least costly and least effective strategy ($178.95, 0.1553 FNs). Biopsy alone was the most costly and most effective strategy ($396.60, 0 FNs). The cost per FN avoided moving from IgG tTG to the other strategies sequentially on the efficiency frontier were $293, $369, $1,401 for IgA EMA, tTG and biopsy respectively.

Conclusion: The evidence available suggests that IgA tTG has a higher accuracy compared to other serologic tests. All testing strategies with biopsy were cheaper than biopsy alone however they also resulted in more FNs. The choice of serologic test will depend on the decision maker’s willingness to pay to avoid a FN. Serologic test combinations contribute little to the diagnostic accuracy with an increased cost.