The Project Assurance ® Difference 1 Adopted Guidance Clinical Execution Planning Design Safety Operational Data analysis Outcome Conclusions

The Project Assurance ® Difference 2 Operational - How to measure the ECGs Acute safety: standard digital ECG machines, telemetric monitoring Thorough QTc analysis: 12-lead continuous digital ECGs Higher costs of Holters balanced by lower clinical costs Standard ECG may miss C max of metabolites In case of safety problems, Holters provide all necessary data Involvement of core ECG-lab

The Project Assurance ® Difference 3 Operational - Collaboration CPU / ECG-lab Continuous exchange of lots of information Equipment: installation + support Flash cards: sending, reading, returning Data: queries, results Project management: planning, progress, contingencies People should know each other Instructions, training Experience Procedures should be synchronized

The Project Assurance ® Difference 4 Operational - Portable equipment for volunteer’s comfort Mortara H-12/H12+ Continuous digital 12-lead ECG High sample frequency Holter analyses Heart rate Arrhythmias Ischemia parameters Heart rate variability H-12 H-12+

The Project Assurance ® Difference 5 Modem, diskette or flash Card Operational – Recording and analysis Paper Digital File Digitize FDA.XML DTD EXPeRT™ Fully-Manual Specialist + MD Algorithmic + MD Collect + Store + Output EXPeRT TM Web-based access via your own internet portal

The Project Assurance ® Difference 6 Adopted Guidance Clinical Execution Planning Design Safety Operational Data analysis Outcome Conclusions

The Project Assurance ® Difference 7 Data Analysis – Time-matched, time- averaged, mean maximum change Time-matched: subtract hour X at baseline from hour X on treatment to obtain a change from baseline for each time point (+/- 95% CI) – primary analysis Time-averaged: subtract time-averaged baseline (one single value as mean of all baseline measurements) from the mean of all measurements on treatment (one single value) (+/- 95% CI) Mean maximum change from baseline: as time- matched, but different time point per subject

The Project Assurance ® Difference 8 Statistical method I Average all Δ 1 ’s (n=50) + ANOVA analysis Average all Δ 2 ’s (n=50) + ANOVA analysis Average all Δ 15 ’s (n=50) + ANOVA analyis Determine the largest average QTci Day 1 Day -1 Δ1Δ1 Δ2Δ2 Δ3Δ3 Δ 15

The Project Assurance ® Difference 9 Statistical method II Average of Δ’s for all volunteers (n=50) + ANOVA analysis QTci Day 1 Day -1 Δ

The Project Assurance ® Difference 10 Statistical method III Determine largest Δ for each volunteer (n=50) Δ 1 in this volunteer Average all 50 largest Δ’s + ANOVA analysis QTci Day 1 Day -1 Δ1Δ1 Δ2Δ2 Δ3Δ3 Δ 15

The Project Assurance ® Difference 11 Click here to continue