Robustness and generalizability of smallest detectable difference in radiological progression

The smallest detectable difference (SDD) reflects that component of a measu re statistically attributable to error from the measurement process itself. As such it is an irreducible component of the inherent variability in meas urements in clinical trials and will affect their design, whether randomize d or observational. Even though the application of the SDD concept to assay ing radiographs in rheumatoid arthritis is relatively new and not well unde rstood, systematic work on the influences of radiographic SDD can be done. This report describes the effects of a number of clinical aspects of the di sease and operational aspects of trials on the values of the SDD of radiogr aphic progression data. We show that if conditions affecting SDD are known and kept constant across datasets, the SDD of radiological progression from one study may be generalizable to other studies. However, if any one condi tion varies, the SDD is distinctly unrobust and cannot be generalized to ot her studies.