Comparative Validation of Five Quantitative Rapid Test Kits for the Analysis of Salt Iodine Content: Laboratory Performance, User- and Field-Friendliness

<div><p>Background</p><p>Iodine deficiency has important health and development consequences and the introduction of iodized salt as national programs has been a great public health success in the past decades. To render national salt iodization programs sustainable and ensure adequate iodization levels, simple methods to quantitatively assess whether salt is adequately iodized are required. Several methods claim to be simple and reliable, and are available on the market or are in development.</p><p>Objective</p><p>This work has validated the currently available quantitative rapid test kits (quantRTK) in a comparative manner for both their laboratory performance and ease of use in field settings.</p><p>Methods</p><p>Laboratory performance parameters (linearity, detection and quantification limit, intra- and inter-assay imprecision) were conducted on 5 quantRTK. We assessed inter-operator imprecision using salt of different quality along with the comparison of 59 salt samples from across the globe; measurements were made both in a laboratory and a field setting by technicians and non-technicians. Results from the quantRTK were compared against iodometric titration for validity. An ‘ease-of-use’ rating system was developed to identify the most suitable quantRTK for a given task.</p><p>Results</p><p>Most of the devices showed acceptable laboratory performance, but for some of the devices, use by non-technicians revealed poorer performance when working in a routine manner. Of the quantRTK tested, the iCheck^® and I-Reader^® showed most consistent performance and ease of use, and a newly developed paper-based method (saltPAD) holds promise if further developed.</p><p>Conclusions</p><p>User- and field-friendly devices are now available and the most appropriate quantRTK can be selected depending on the number of samples and the budget available.</p></div

Summary of results from the ‘method’ validation of the different quantRTK’s.

<p>^a LoD, limit of detection; LoQ, limit of quantification; for the description of the calculations, refer to the description in the method section;</p><p>^b three iodine levels were used (15.0, 29.6, 59.1 mg/kg) and the three CV’s are given in the order of increasing iodine concentration;</p><p>^c Recovery A was calculated from the linearity assessment, and results are presented as mean recovery ± SD; Recovery B was calculated from the inter-operator precision exercise and comprises the observed/expected values from the samples with approximate KIO₃ concentrations of 15, 20, 30, 45, 60, and 90 mg/kg; results are shown with % SD.</p><p>^d the device gives results in mg/L and anything above 13mg/L is indicated as 'above measuring range'; assuming 1:5 dilution (factor 5.45), this corresponds to 65 mg/kg;</p><p>^e The device has set working ranges from 15–50 mg/kg and thus, LoD and LoQ could not be assessed; further, for intra- and inter-assay imprecision and recovery, the low level of salt (15.0 mg/kg) could not be assessed; the high level yielded results, because the device gave consistently lower readings; n/d thus, means not determined;</p><p>^f For the saltPAD, three types of interpretation of the results on the cards were done: interpretation by the operator, by an expert reader (a person from the device developer) and an image analysis software; for the device performance, the expert reader’s results only were used.</p><p>Summary of results from the ‘method’ validation of the different quantRTK’s.</p

Bland-Altman’s Limits of Agreement (LOA).

<p>^a Provides the number of samples with a valid quantitative result (i.e. not below or above the measuring range);</p><p>^b Difference between the reference method and the respective quantRTK;</p><p>^c Difference between the reference method and the quantRTK ±2 SD.</p><p>^d For the saltPAD, three types of interpretation of the results on the cards were done: interpretation by the operator, by an expert reader (a person from the device developer) and an image analysis software; the index provides the information which readings were used.</p><p>Bland-Altman’s Limits of Agreement (LOA).</p

Overall assessment of the quantRTK included in the validation, including objective and subjective parameters.

<p>^a Overall rating: (2*Analytical performance+user friendliness+field readiness+low resource setting suitability)/5;</p><p>^b These devices are not yet commercially available and under further development; thus, the scores are of transient nature.</p><p>Overall assessment of the quantRTK included in the validation, including objective and subjective parameters.</p

Summary of the results from the ‘system’ validation: inter-operator imprecision, expressed as coefficient of variation.

<p>^a three iodine levels were used (15.0, 29.6, 59.1 mg/kg) and the three CV’s are given in the order of increasing iodine concentration;</p><p>^b three iodine levels were used (20.0, 47.5, 90.4 mg/kg) and the three CV’s are given in the order of increasing iodine concentration;</p><p>^c outside of measuring range for more than one measurement and thus, n/d means not determined.</p><p>^d For the saltPAD, three types of interpretation of the results on the cards were done: interpretation by the operator, by an expert reader (a person from the device developer) and an image analysis software; the index provides the information which readings were used.</p><p>Summary of the results from the ‘system’ validation: inter-operator imprecision, expressed as coefficient of variation.</p

Schematic presentation of rating matrix employed.

<p>Schematic presentation of rating matrix employed.</p