Thanks to scientific advancements and increased understanding of pathways and systems that contribute to cardiac risk, the cardiac safety ECG environment continues to mature and expand. Presently, the assessment of QT/QTc from the electrocardiogram is the primary focal endpoint in cardiac safety.
Examining the progress made over the past decade takes me back to 2006 when early discussions around implementation of ICH E14 guidance were taking place. It was at DIA’s annual conference that year where I had the opportunity to organize a session, QT Dossier – The Impact of ECG Data from a Regulatory Perspective, in a panelist discussion with the FDA and industry representatives.Since then, we’ve had a lot of thoughtful and productive discussion within the industry, resulting in some important Q&A around ICH E14.
Initially, when the ICH-E14 came out proposing/requiring the conduct of a dedicated study to evaluate the QT effect ─ the Thorough QT (TQT) study ─ there was concern over cost and the impact on drug development this additional study would have. Fortunately, through advancement in TQT trial design, industry market pressures and other factors, the cost of a TQT study is actually lower today than the initial TQT studies conducted when the ICH-E14 was initially implemented.
Advancements and direction for evaluating the cardiac safety during the drug development process are highlighted in the most recent ICH-E14 Q&A and the ensuing cardiac safety conferences and industry meetings. One discussion centers on whether or not a formal TQT is necessary as part of the development program, with more of a focus on exposure response/ concentration effect analysis associated with the QT.
With the responses to the ICH E14 Q&A and options available to address cardiac safety requirements for developing therapeutic treatments/compounds, there are some key “points to consider” from a drug development consideration. These include:
- What are the potential financial considerations and impact for the biopharmaceutical organization when determining which trial design and path to take to address the cardiac safety regulatory requirements
- For biopharmaceutical organizations developing a compound, how do they determine the best path and types of trials to conduct to address the cardiac safety requirement?
- Is it still appropriate to conduct and submit a formal TQT study?
A number of these discussion points have been raised during industry meetings, including a review of a potential decision tree approach to assist in defining approaches to trial design and considerations.
These are but a few of the topic points that Bioclinica’s cardiovascular safety & medical imaging team will be exploring at upcoming industry conferences, meetings and webinars. We’d love to hear your perspectives and insights, so please join us during our forthcoming interactive webinar entitled, “Cardiovascular Safety in Biopharmaceutical Product Development – From QT Prolongation and Beyond“ and/or drop me a line anytime!