Cardiac Safety Analysis Suite 5 Modules

Comprehensive cardiac safety simulation tools for ICH E14/S7B compliance, TQT study design, biomarker monitoring, and exposure-response modeling. Select a module below to begin.

QRS

QT/QTc Concentration-Response (C-QRS) Nav1.5 exposure-response with BLQ sensitivity per Garnett 2018

CORE

TQT

TQT Study Power Calculator Thorough QT study design with crossover power analysis

NEW

ECG

ECG Categorical Analysis ICH E14 categorical outlier assessment by dose group

NEW

BIO

Cardiac Biomarker Dashboard Troponin-I, BNP, CK-MB monitoring with fold-change analysis

NEW

E-R

Cardiac Event Exposure-Response Logistic regression for cardiac AE probability vs exposure

NEW

P Compound Profile

Select a preset scenario or customize parameters for C-QRS exposure-response modeling.

Gut-Restricted Oral

Systemic Oral

IV Antiarrhythmic

Custom

Low Dose ? mg (e.g., 200 mg BID)

Target Dose mg (e.g., 800 mg BID)

Supratherapeutic Dose mg (highest dose tested)

Subjects per Arm per active arm (placebo = 30)

BLQ Rate at Target Dose ? % (higher = more gut-restricted)

True C-QRS Slope ? ms per ng/mL

LLOQ ng/mL

Baseline QRS ms (population mean)

Concentration-QRS Exposure-Response Relationship

DDeltaQRS by Dose Group (90% CI)

BLQ Sensitivity: Observed vs M5 (LLOQ/2)

QRS Change from Baseline Over Time

CSRC Outlier Analysis

O Categorical Outlier Incidence (CSRC Criteria)

B BLQ Method Comparison

Methodology References

Garnett CE et al. (2018) Scientific white paper on concentration-QTc modeling. J Pharmacokinet Pharmacodyn 45:383-397.

Harmer AR, Valentin JP, Pollard CE (2011) On the relationship between block of the cardiac Na+ channel and drug-induced prolongation of the QRS complex. Br J Pharmacol 164:260-273.

ICH E14/S7B Q&As R3 (2022). Questions and Answers on clinical and nonclinical evaluation.

Note: Simulated data for educational and planning purposes only.

T TQT Study Design Parameters

Configure thorough QT study parameters for power and sample size calculation.

Standard TQT

Small Effect

Large Effect

Custom

Expected DDeltaQTc Effect ? ms

SD of DeltaQTc ? ms

N per Sequence subjects

Alpha (One-Sided)

Number of Time Points ? per treatment period

Non-Inferiority Margin ms (ICH E14 default = 10 ms)

Power Curve: Sample Size vs Statistical Power

Effect Size Sensitivity Analysis

Minimum N by Power Target

S Sample Size Recommendation

E ECG Categorical Outlier Parameters

Assess ICH E14 categorical QTc outliers across dose groups.

Clean Profile

Borderline

Concerning

Custom

N Subjects per Group

Number of Dose Groups (excl. placebo)

Categorical Outlier Rates by Group (%)

Group	QTc >450ms (%)	QTc >480ms (%)	QTc >500ms (%)	DeltaQTc >30ms (%)	DeltaQTc >60ms (%)

Categorical QTc Outlier Incidence by Dose Group

Change from Baseline Outliers (DeltaQTc)

Traffic Light Summary

T Traffic Light Assessment

B Cardiac Biomarker Configuration

Configure Troponin-I, BNP, and CK-MB levels across dose groups for cardiac biomarker assessment.

Normal Profile

Mild Elevation

Significant Signal

Custom

Number of Dose Groups (excl. placebo)

N Subjects per Group

Troponin-I ULN ? ng/mL

BNP ULN pg/mL

CK-MB ULN ng/mL

Biomarker Levels by Group (Mean +/- SD)

Group	Trop-I Baseline	Trop-I Post-Dose	BNP Baseline	BNP Post-Dose	CK-MB Baseline	CK-MB Post-Dose

Cardiac Biomarker Fold-Change from Baseline

Troponin-I Levels vs ULN

BNP and CK-MB Summary

T Traffic Light Summary

E Cardiac Event Exposure-Response

Model the relationship between drug exposure (AUC) and cardiac adverse event probability using logistic regression.

Low Risk

Moderate Risk

High Risk

Custom

Dose Group Data

Dose Group	N Subjects	Cardiac AE Count	Mean AUC (ng*h/mL)

Logistic Regression: Cardiac AE Probability vs Exposure

Observed Event Rate by Dose Group

Risk Threshold Analysis

R Risk Assessment Summary