MOMS (MULTIPLES OF THE MEDIAN) AND DADS (DISCRIMINANT ANEUPLOIDY DETECTION) - IMPROVED SPECIFICITY AND COST-EFFECTIVENESS OF BIOCHEMICAL SCREENING FOR ANEUPLOIDY WITH DADS

OBJECTIVE: Our purpose was to assess the efficacy of double- and tripl e-screening paradigms for Down syndrome and to develop a more logical, statistical approach to risk prediction that will decrease the cost o f screening and allow the incorporation of new parameters appropriatel y weighted for their contribution. STUDY DESIGN: Data from 24,504 pati ents who had biochemical screening for Down syndrome by single (alpha- fetoprotein), double (alpha-fetoprotein, beta-human chorionic gonadotr opin), or triple screening (alpha-fetoprotein, beta-human chorionic go nadotropin, unconjugated estriol) who had complete outcome information were analyzed by (1) existing gaussian-based methods, (2) the Glasgow ratio method, and (3) a new statistical approach (i.e., directly adju sted data sets for discriminant aneuploidy detection [DADs]). RESULTS: By use of individual risk-based thresholds for ''at risk'' status, bo th double and triple screening performed far better than single screen ing, but the percentages of patients at risk varied widely. When the p ercentages at risk were held constant, the sensitivity of double and t riple screenings was similar, suggesting that there are no benefits of using estriol as a third marker. For 25,000 patients the use of only alpha-fetoprotein and beta-human chorionic gonadotropin would save abo ut $500,000, with no decrease in sensitivity. With the DADs approach a statistically sound model giving more stable estimates was developed that permits each factor to be analyzed for its own explained proporti on of variance and allows each parameter to have different weighting. For this data set the same sensitivity was seen with, conservatively, a 1% reduction in the percentage of patients at risk, which would redu ce by 250 the number of amniocenteses, at a further savings of about $ 400,000. CONCLUSIONS: By use of existing methods, double screening is equally as effective as triple screening, so that the expense of estri ol is unnecessary. The DADs approach, by allowing for variable weighti ng of parameters, lowers the at risk percentage and will permit a much more flexible approach as new parameters become available. Changing t o DADs and eliminating estriol should achieve higher specificity for t he same sensitivity and save, conservatively, about $900,000 in this s eries. Extrapolated nationally, if confirmed, the annual savings could approach $72,000,000.