Precision of risk in multidimensional likelihood ratio based screening with first trimester screening for Down's syndrome as a special case

Objectives-The development of computer programs for the calculation of risk s and Monte Carlo estimation of the precision of such risks in Likelihood r atio based screening with multiple gaussian distributed risk markers and a priori risks. A quantitative study of the variation of risk estimates in fi rst trimester screening for Down's syndrome as a function of the variation of markers, and comparison of the results with published information on the variation of risk estimates in quality control schemes. Methods-Algorithms for calculations in the multidimensional normal distribu tion and procedures for Monte Carlo simulation of risk distributions were i mplemented in the S-PLUS programming language and used to construct program s producing risk estimates and risk distributions. Parameters of risk marke r distributions and correlations were obtained from the scientific literatu re. Results-In screening for Down's syndrome during the first trimester the var iation in risk estimates increased with increasing variation of biochemical and biometric markers, and the a posteriori risk may vary with at least a factor of 2-4. Conclusions-Risk estimates are not reasonable parameters in quality control systems. Instead, screening programmes should be controlled through carefu l monitoring of the distribution of risk estimates, in particular the scree n positive rate, and control of the quality of the biochemical and biometri c data. Furthermore, the correct classification of samples submitted for pr oficiency testing into screen positive and screen negative cases should be checked.