QT monitoring is essential in clinical trials for assessing the cardiac safety of new drugs. This process, critical across the spectrum of drug development, is necessary for comprehensive safety evaluations before market approval. Beyond its traditional focus on cardiac-specific therapies, every investigational drug has the potential to impact cardiac function, emphasizing the importance of QT monitoring for sponsors aiming to optimize their drug development process.
QT monitoring is pivotal for sponsors, enhancing more than just safety; it helps streamline development pipelines through early-phase comprehensive safety assessments. This contributes to reducing time to market entry and easing regulatory processes, while insights gained allow for greater opportunities in treatment personalization. This enables sponsors to refine patient selection for future trial phases, and improve the prospects of trial success.
The broad utility of QT monitoring highlights its essential role across various therapeutic areas. Here are some key applications:
Safety Assessments: QT monitoring can ensure that the drug under investigation does not have a detrimental effect on cardiac repolarization, which can lead to arrhythmias. For instance, in oncology, it can be used to identify early cardiac risks associated with new treatments, and in diabetes to develop safer antidiabetic medications with reduced cardiovascular risk profiles.
Regulatory Compliance: Regulatory agencies like the FDA and EMA mandate QT interval assessment for most new drugs as part of their safety evaluation process. Demonstrating that a drug does not significantly affect the QT interval is often a requirement for approval. The FDA states that all "Drugs are expected to receive a clinical electrocardiographic evaluation beginning early in clinical development, typically including a single trial dedicated to evaluating their effect on cardiac repolarization ('thorough QT/QTc study')".¹
Drug Differentiation: Demonstrating a neutral or lesser impact on the QT interval for drugs in the same therapeutic class can be a distinguishing safety feature. When comparing the effectiveness of a new drug against existing treatments or a placebo, as often is done with antipsychotic medications, a favorable QT profile can serve as a key differentiator—especially in competitive markets.
Dose Finding: QT monitoring helps in identifying the safe dose ranges of a drug. For example, researchers can examine how different doses of opioids impact the QT interval to establish optimal dosing regimens that minimize the risk of cardiac arrhythmias while maximizing pain relief. By determining the dose-response relationship with respect to QT prolongation, researchers can optimize dosing regimens to minimize risk.
Patient Selection and Risk Management: By identifying patient populations that may be more susceptible to QT prolongation (e.g., patients with existing QT conditions or those taking other QT-prolonging medications), sponsors can design trials that are safer and more targeted. This personalized approach can enhance the trial's success rate and patient safety.
Given the clear benefits of QT monitoring in enhancing drug development and trial safety, it's natural to wonder why its application isn’t more widespread across diverse drug trials. The answer often lies in the challenges posed by traditional 12-lead (12L) ECGs, which require on-site clinic visits and bulky equipment, placing physical burdens on patients.
Recent innovations, however, are breaking down these barriers, allowing for more precise and flexible QT monitoring solutions. For example, AliveCor has launched a pocket-sized, handheld 12L device for use by physicians, providing a trusted alternative to traditional 12L systems. However, for decentralized or hybrid trials, where ease of use and remote QT monitoring are key, the KardiaMobile® 6L serves as a vital complement.
With KardiaMobile® 6L, trials become:
A study on digital technologies in clinical trials even suggests that "The density and continuous nature of the data collected, particularly during early drug development, could support earlier detection of adverse events and allow for more optimized dose titration outside of office visits. Furthermore, continuous data output creates an opportunity for the development of novel endpoints that were previously inaccessible via traditional clinical trials."²
With KardiaMobile® 6L, sponsors can reliably monitor QT intervals at every trial stage—no matter the drug.
With greater access to QT data and integration of advanced monitoring technologies can come greater trial successes benefitting sponsors, participants, and ultimately, patients.
Ready to harness the benefits of QT monitoring in your clinical trials? Discover how KardiaMobile® 6L can innovate your approach today.
Resources:
https://www.cancertreatmentreviews.com/article/S0305-7372(17)30201-3/pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946151/
https://karger.com/mpp/article/27/5/401/204443/Opioids-and-Cardiac-Arrhythmia-A-Literature-Review
https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm
https://www.fda.gov/media/71379/download
*QT measurements made using EK12 ECG algorithm.
¹ "Guidance for Industry: E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs." U.S. Department of Health and Human Services. October 2005.
² Mitsi G, Grinnell T, Giordano S, Goodin T, Sanjar S, Marble E, Pikalov A. Implementing Digital Technologies in Clinical Trials: Lessons Learned. Innov Clin Neurosci. 2022 Apr-Jun;19(4-6):65-69. PMID: 35958972; PMCID: PMC9341314.
Beyond its traditional focus on cardiac-specific therapies, every investigational drug can potentially impact cardiac function. What if we expanded QT monitoring across various therapeutic areas?
Wiley.com | Clinic utilization time is significantly reduced with the KardiaMobile® 6L compared to traditional 12L ECG systems. This study published in Wiley highlights how the 6L minimizes the need for frequent conventional 12L use.
JAMAnetwork.com | Patient-centric trials require accessible digital health technologies. A JAMA study explores the current state and aspired role of remote monitoring and data collection tools in oncology trials.