A systematic review of 55 clinical trials revealed that 90% of Long QT Syndrome trials using point ECGs failed to report time of day information, highlighting a critical gap in trial design.
Systematic Review (n=55)
Does the design of clinical trials for Long QT syndrome adequately utilize diurnal timing information for ECG measurements and drug delivery?
Clinical trials for Long QT syndrome frequently fail to incorporate diurnal timing information for ECG measurements and drug dosing, potentially compromising the interpretation of trial results.
Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.
Seed et al. (Tue,) conducted a systematic review in Long QT Syndrome and drug-induced QT prolongation (n=55). Integration of diurnal timing information vs. Standard trial design without diurnal timing was evaluated on Proportion of trials reporting time of day information for ECG measurement or drug administration. A systematic review of 55 clinical trials revealed that 90% of Long QT Syndrome trials using point ECGs failed to report time of day information, highlighting a critical gap in trial design.