Time-series analysis in the medical domain: A study of Tacrolimus administration and influence on kidney graft function

There exists a major concern regarding toxic effects of immunosuppressive medication on the kidney graft during post-transplant care, with observed variation in individual susceptibility to adverse drug effects amongst patients. To date, there has been no possibility to identify susceptible patients prospectively. This study analyzes medical data which includes time series of measures of renal function and trough levels of immunosuppressive drug Tacrolimus, with the main aim of identifying patients susceptible to drug toxicity. We evaluate a plethora of time-series distance measures, determining their appropriateness to the domain based on two criteria: (1) preserving the expected correlations between distances, and (2) ability to detect the expected patterns of interaction between immunosuppressive drug levels and renal function. Besides identifying the most suitable time-series distance measures, we observed that the majority of patients do not exhibit an association between impaired graft function and higher Tacrolimus dosing. On the other hand, the minority of patients determined most sensitive to varying Tacrolimus levels showed a strong tendency to prefer low Tacrolimus dosing.