Response to Basu et al

We welcome the critique of our paper ¹ by Basu et al. ² The analytical challenges of free light chain (FLC) assays are well documented^3,4 and need to be considered when evaluating an alternative method. The precision study was performed at the correct sample dilution as recommended by the manufacturers. The results are a reflection of the performance of the assays and are similar to those reported elsewhere. ⁴ We note a lack of references to contradict our findings. Selecting samples to uniformly cover the measurement range is an elemental aspect of method comparison studies and avoids evaluation of skewed data with a limited range. ⁵ As stated, we recruited samples for the method comparison based on the Freelite result until we had sufficient numbers in each category. The distribution of results relative to the proposed cut-off points led to our discussion on reference ranges which we qualified by pointing out the need for a formal reference range study. The recommendation that we should repeat discordant results at different dilutions is interesting and we refer the authors to Table 1. ¹

The requirement that a new assay must be validated de novo in clinical studies before use needs to be carefully considered. Both the Freelite and N Latex assays are approved for clinical use by the relevant regulatory authorities and furthermore the guidelines do not appoint an exclusive manufacturer. In our opinion the clinical usefulness of an assay does not require perfect alignment with a ‘predicate’ assay, a point that is very well illustrated by the Freelite assays as clinical validation studies are not called for each batch of reagent and every analytical platform, despite considerable variation.^3,4

After consideration of our data and the comments by Basu, we maintain our opinion that the N Latex FLC assay can be used in clinical practice based on its analytical performance characteristics.