Response to the Comments on 'Point of Care D-Dimer Testing in the Emergency Department-A Bioequivalence Study' and Erratum to the Results

We have read with interest the comments made on our study titled ‘Point of care (POC) D-dimer testing in the Emergency department–a bioequivalence study’ [1]. Ekelund and Heilmann, referring to the results and conclusions of the study, have suggested that one of the discrepancies may be caused by a typographical error, and this inference probably stems from the use of the term ‘range’ in the published article. This should have been termed ‘Bland-Altman limits of agreement’ (0.24-2.13) for all the cases where both tests were ordered and not just for the 8 POC-negative VIDAS (VIDAS D-dimer assay; bioMérieux SA, RCS Lyon, France)-positive patients. The data have been reconfirmed by our database as not being a reporting error. Our study reflects a real-life scenario of replacing an existing laboratory test within the emergency department with another POC assay (AQT90 FLEX POC D-dimer analyzer; radiometer medical ApS, Åkandevej, Denmark). This involves conducting a bioequivalence study between the two assays to rule out the risk of missed positive results–the outcome by which clinicians would be guided. Raising the cut-off values, including age-appropriate cut-offs has been suggested in the literature as a measure to improve the specificity of D-dimer assay and reduce the implications of radiological investigations for various subsets of patients [2-7]. Furthermore, a separate study on the sensitivity and specificity of D-dimer test in venous thromboembolism is in progress. As pointed out in the results of our study, the POC D-dimer assay demonstrated better specificity than the VIDAS assay; however, our study was neither designed nor powered to investigate this question as the primary outcome measure. If statistically proven in a larger cohort of patients, the improved specificity of POC Ddimer assay may reduce the risk of unnecessary radiation or other interventions for a subset of patients, which could be considered as a significant strength of the assay. As pointed out by Sukhu et al. [8], discordant values are increasingly obtained near the cut-off levels leading to mismatched results between the two assays, therefore, a larger study would be required before implementing a new methodology in a clinical setting. A study on bioequivalence between the two assays was not enough to make an informed decision to replace one test with the other, a conclusion also supported by Sukhu et al. [8] in their study. The criteria for bioequivalence studies and cut-offs for drugs are well established [9, 10], but the question can be raised whether the same standards can be applied for bioequivalence of diagnostic assays, especially in diseases of low prevalence [11]. Our study results show that the 8 patients who were tested positive by the VIDAS assay demonstrated negative POC D-di-