Deriving reference limits from historical data - A comparison of four novel methods

To compare four novel methods - extrapolated norms (E-norms), extrapolated reference values (E-Ref), multivariable extrapolated reference values (MeRef) and mixture model clustering (MMC) - for obtaining reference limits for nerve conduction studies (NCS) from historical data containing both normal and abnormal studies.

Reference limits for 29 commonly clinically used NCS measurements were calculated from a historical database containing measurements from 24618 patients using E-norms, E-ref, MeRef and MMC. The resulting reference limits were compared to reference limits for NCS calculated from 680 healthy subjects using Youden's J statistics.

Except for distal latencies, E-norms produced reference limits with the highest Youden's J statistics with higher sensitivity, but lower specificity. E-Ref, MeRef and MMC produced reference limits with high specificity, but lower sensitivity than E-norms.

There are substantial differences in the performance of E-norms, E-Ref, MeRef and MMC. A dynamic approach, where the methods used are changed based on the type of NCS measurement and the amount of historical data available, may yield the highest accuracy.

When combining the different novel methods, it is possible to create clinically useful reference limits using historical data.