Amidst the groundbreaking technological advancements that clinical research has seen in recent years, there are still some areas in which the industry is looking for improvements. One of these is FDA approval rates. Only about ten percent of drugs that enter clinical trials ultimately make it to market, rendering lost the years and, often, billions of dollars spent developing many drugs. Inaccuracies in data collected during research is a major reason why these drugs don’t make it to approval. In this context, clinical research stands to benefit significantly from any innovation that can increase efficiency and accuracy in drug development.
One such innovation comes from iCardiac Technologies, which has developed a new method for assessing the cardiac safety of new drugs – specifically, how a drug affects a patient’s QT interval – in a way that could significantly shorten, and reduce the costs of, the drug development process. The approach demonstrated effectiveness in a prospective validation study that was summarized by the FDA at the end of 20141, and is now gaining favor among industry regulators. In discussing this new method, it’s best to consider it in contrast to the current norm in cardiac safety assessment.
Traditional Methods of Cardiac Safety Analysis
Given the potential seriousness of heart irregularities in humans, one might imagine that one of the primary purposes of the safety and tolerability assessments that take place in Phase I studies would be to analyze a compound’s effect on the heart. Since 2005, though, in accordance with a mandate from regulators, researchers have, with some exceptions, analyzed the effect of a drug on patients’ QT intervals in designated studies separate from the rest of the clinical research process2. These studies, called Thorough QT (TQT) studies, take place in the middle and later phases of clinical research, and allow researchers to focus solely on cardiac safety.
The strength of these studies is that they allow for the exclusive focus that regulators and many sponsors feel cardiac safety deserves. But some sponsors and innovators have seen opportunities for improvement in efficiency and accuracy. In some TQT studies, for example, clinically insignificant heart irregularities have led to false diagnoses of cardiac problems. This has created a market for an alternative methodology for assessing cardiac safety, one that can produce accurate data without compromising thoroughness, and do so in a way that can keep the costs and timeline of drug development at bay.
The Alternative Method of Cardiac Safety Analysis
After the prospective validation study at the end of 2014, it appears such a methodology has arrived. Here’s how that methodology, called Early Precision QT, works.
TQT studies utilize cardiac safety data collected from an electrocardiogram (ECG); with Early Precision QT, this process is incorporated into otherwise routine Phase I studies instead of separated from the main phases3. If a study design implements this method, then analysis of a drug’s QT effect will be performed closer to the beginning of the research process, in Phase I, instead of in the middle or later phases. This could amount to a difference of several years in the drug development timeline, and allow researchers to apply for an exemption from traditional TQT studies. The work done by researchers will be largely the same – data will still be collected and assessed with the ECG – it will simply happen at a different point in the process.
Early Precision QT has demonstrated multiple benefits. In the prospective validation study, the data was analyzed accurately, without false diagnoses1. Furthermore, the method can yield significant cost savings. By integrating QT analysis with routine Phase I studies, it eliminates the need to fund an entirely separate study in the later and more expensive stages of drug development. And if the results of the assessment lead to the conclusion that the treatment is unsafe, and the study is canceled, the sponsor will have lost significantly less of their investment than if that conclusion were reached later in development.
Last December, regulators revised their guidance for QT data-gathering methods to allow for this new approach to QT assessment2. Early Precision QT is not, however, mandatory. The TQT studies currently in practice have their merits, and many sponsors may prefer to continue using them. Early Precision QT simply creates more flexibility in how sponsors can assess a drug’s effect on patients’ QT intervals. And as the method is proprietary, sponsors who wish to implement it will need to reach an agreement with the company that developed it. Those who do may see a rearrangement of some key steps of the drug development process, and could significantly boost the efficiency with which clinical research is conducted.
It is, of course, fanciful to hope for one hundred percent approval rates – but if a new system truly can offer shorter timelines and fewer inaccuracies, more treatments may indeed be approved – and sponsors of those that don’t may feel less of a sting.
1 FDA: Study Demonstrates Potential for Faster Drug Development; iCardiac Technologies, Inc.; 15 December 2014
2 Kleiman, Robert; Are You Prepared to Replace the Thorough QT study?; Applied Clinical Trials; 15 June 2016