Optimizing Study Enrollment
Optimizing Study Enrollment by Minimizing Unreliable ECG Data
Ensuring that no subjects are needlessly excluded from a study because of inaccurate ECG data collected at a screening visit can save considerable time and costs. We can rapidly analyze your screening ECGs to make sure your sites are making the correct decisions about whether subjects should be included or excluded. This process can help to speed up study recruitment, and ultimately achieve earlier database lock.
How ECGs affect subject recruitment
The International Committee on Harmonization Guidance (ICH E14) has defined key requirements for the conduct of cardiac safety evaluation in clinical trials as well as inclusion criteria for Phase II and Phase III studies in the absence of definitive knowledge of a compound’s cardiac safety:
- Prior to characterizing a drug’s QT liability (typically achieved as part of a Thorough QT Study), all subjects with a marked baseline prolongation of QT/QTc interval are generally excluded from any clinical studies. As a result, patients with a measured QTc interval in excess 450 milliseconds during screening for a late phase study are often excluded from the trial.
- Relying on automated algorithms from site-based ECG machines often produces falsely elevated QT measurements, causing unnecessary patient exclusions and lower recruitment yields.
- This requires that additional subjects be screened to replace subjects who are excluded due to QT prolongation.
- QT prolongation is associated with a broad range of disease states, including liver disease, oncology, diabetes, rheumatoid arthritis and many central nervous system conditions, where the share of subjects who have measured QT prolongation can range from 5% to as much as 70% of all subjects. QT prolongation is also associated with conditions common to clinical trial subjects across all disease areas, including old age, obesity, depression, anxiety and sleeplessness.
- Once QT liability has been accurately characterized, subjects with a measured QTc in excess of 450 milliseconds may often no longer need to be excluded and, as a result, recruitment can be accelerated.
Onsite machine read vs. centralized iCardiac QT reporting
- Improved accuracy and precision through centralization means faster recruitment and faster database lock, saving significant costs during Phase II and III studies. Rapid, accurate, centrally-read ECGs eliminate unnecessary patient exclusions related to common, falsely-elevated, machine-interpreted QT intervals from site-based equipment:
- ECGs interpreted by a machine’s internal algorithms do not provide the accuracy needed to minimize false positive and inconclusive results.
- These false positive and inconclusive results lead to exclusion of otherwise viable subjects, raising costs and increasing time required to complete trials.
- Case studies from recently re-analyzed late phase studies at iCardiac show an average of 28% false positives in 3 categorical ranges (>450 ms, >480 ms, >500 ms).
- The primary limitation of most core ECG laboratories is reporting the accurate QT result back to the site before the patient exits the facility and/or is excluded from the trial.
- With iCardiac’s Dynamic ECG Centralization, data is analyzed and returned within 2 to 4 hours of reading, while the patient is still onsite or available to be randomized.
- All data is supplied in a consistent digital format that is securely accessible from any location for any required cardiologist assessment. The data is saved in permanent searchable archive that can be instantly accessed at a later date, streamlining interim or final review of all cardiac safety for end-of-study reporting.