3 research outputs found
Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project.
Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project.
Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass
215 spectrometry through a worldwide collaboration. Methods: Cumulative percentiles of amino
216 acids and acylcarnitines in dried blood spots of approximately 30 million normal newborns and
217 10,615 true positive cases are compared to assign clinical significance, which is achieved when
218 the median of a disease range is either >99%ile or <1%ile of the normal population. The cutoff
219 target ranges of analytes and ratios are then defined as the interval between the limits of the two
220 populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity
221 taking in consideration all available factors. Results: As of December 1, 2010, 129 sites in 45
222 countries have uploaded to the project website a total of 23,970 percentile data points, 558,168
223 analyte results of 10,615 true positive cases with 64 conditions, and 5,088 cutoff values. The
224 average rate of submission of true positive cases between December 1, 2008 and December 1,
225 2010 was 4.7 cases per day (3,418 cases). This cumulative evidence generated 91 and 23 high
226 and low target cutoff ranges, respectively. The overall proportion of cutoff values within the
227 respective target range was 43% (2,176/5,088). Conclusions: An unprecedented level of
228 cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114
229 markers applied to newborn screening of rare metabolic disorders. This set of data could be used
230 as baseline for monitoring of future performance
Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project
PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. © 2011 Lippincott Williams & Wilkins