A good CRO should be able to provide clients with FDA compliant manual over-read QT interval analysis and measurement by a team of experienced and highly trained cardiologists. Using the FDA compliant manual over-read approach, the QT interval is measured on screen by cardiologists through the use of electronic calipers (MUSE CV® Interval Editor, GE Marquette Medical Systems) with sufficient magnification that allows for the measurement precision equal to the storage frequency of 500 MHz, i.e. ±1 ms. Whilst the CRO can discuss and agree on the details of the analysis with the clients at the study design stage, as a matter of routine, in each ECG the QT interval is measured in all 12 leads. The median QT interval of all measurable beats from the 12 leads is then taken as valid for that specific ECG.
A conventional population-derived formulae (e.g. Fridericia) or an individually derived formula is then used to correct the measured and verified QT intervals for heart rate. The QT/QTc interval data are then subjected to a statistical analysis in accordance with the current regulatory guidelines which also includes input and interpretation of the results from experienced cardiological scientists.
In line with the current regulatory requirements and at least every six months, all cardiologists working for a good CRO should undertake intra- and inter-reader variability tests under blinded conditions to ensure that their measurements are reproducible and accurate. Moreover, systematic in–process QC checks should be performed by a senior cardiologist during a specific study analysis. All QC checks and any corrective actions should be reconciled and fully documented.
Every good CROs Core ECG Laboratory team should comprise of highly experienced cardiologists. Moreover, the CRO should ensure that the laboratory team always implements the 3 key elements to producing a successful TQT study, which are:
- Appropriate study design
- The quality of the ECG’s produced during the conduct of clinical trials
- The quality of the ECG analysis
A good way for the CRO to fulfill these 3 important elements would be to place these studies with research units that are able to provide both the conduct, analysis and interpretation of TQT studies. Partner with a CRO that is able to provide you with this combined competence. The CRO should be able to provide you with sufficient data in a format that is FDA compliant, with the inclusion of fewer volunteers, coupled with the production of fewer ECGs with a higher quality level and less variability. This is the key to success for the CRO both with their clients and internally.
Go for a clinical research organisation with a Core ECG Laboratory that has worked with numerous clinical units across the globe, as well as participated in numerous clinical trials that were sponsored by pharmaceutical companies. What you want is to partner with a CRO that has the capacity of undertaking and subsequently analyzing various cardiological assessments in order to understand and explain any abnormal ECG data that may have been obtained during clinical studies of a new chemical entity.