The J to T-peak interval as a biomarker in drug safety studies: A method of accuracy assessment applied to two algorithms.

OBJECTIVES

To evaluate performance of J-to-T-peak (JTP) measurements of 12-lead ECGs, in a five-arm study using drugs with various levels of electrolyte channel block.

METHODS

The novel evaluation method distinguishes between different aspects of measurement. "Random noise" is the variability among repeated measurements made without changing the conditions. "Context noise" is the variability of changes in context of the measurement, e.g. T-wave morphology, autonomic nervous system state.

RESULTS

The average random noise of our RR-corrected JTPc measurements in standard deviations was 3.0 ms and not dependent on the drug. The average context noise was 4.0 ms for ranolazine, verapamil, and placebo, and 8.8 ms for dofetilide and quinidine. Measurement consistency is corroborated by linear fit confidence intervals of baseline- and placebo-corrected JTPc versus drug concentration.

CONCLUSIONS

Systematic differences were found in JTPc drug response between the Mortara method and published data. Residual signal component in the context noise may influence future study design.