TQT study

As many new drugs are subjected to a TQT study, the FDA will receive more and more information from sponsors. In order to capture all the data in submissions in a single location for future reference, and for future data analysis, a database with an analytical tool—the Qtech— was developed in the Office of Clinical Pharmacology and Biopharmaceuticals within the FDA (15). The QTech is a Visual Basic... 

The Thorough QT/QTc (TQT) Study is addressed by ICH Guideline E14 (ICH 2005). It is discussed in more detail in Chap. 7, but a brief description here is appropriate to faciUtate discussion of the role of the intersection-union test in this context. 

The labs that analyze ECGs collected during a TQT study are highly specialized for this purpose and are referred to as core ECG labs. This nomenclature is similar in intent to the term central lab central labs are used to analyze different types of... 

ICH E14 proposed that several values should be reported when presenting the results from a TQT study. These include the following ... 

The TQT study is a randomized, placebo- and positive-controlled clinical trial that can adopt a crossover design or a parallel-group design. The traditional four treatment arms are as follows ... 

The statistical details of the intersection-union and union-intersection tests used in the analysis of QTc data following the completion of a TQT study were provided in Chap. 5 since we believe that readers interested in that level of detail should have access to it within this book. That said, our discussions in this chapter are couched in more simple nomenclature. 

The descriptions in the preceding section apply to the traditional TQT study. Other considerations, however, are also pertinent, particularly as they tie into later discussions in Chap. 10 concerning the cardiotoxicity of many oncologic agents. 

Being as Thorough as Possible When a Formal TQT Study Is Infeasible... 

As we have seen, the traditional TQT study contains a placebo arm. In cases where the study is conducted using healthy participants, there is no ethical concern by definition, these individuals do not have a disease requiring treatment. However, placebo treatment (alone) is not an ethical option in certain circumstances. Rock et al. (2009) therefore discussed alternate approaches when optimum ones are infeasible. Consider the case of developing oncologic drugs. It is well known that many of these drugs are toxic and that cardiotoxicity is relatively common. Therefore,... 

Several potential replacements of the active pharmacological control treatment arm in a TQT study with another means of establishing assay sensitivity have been discussed in the literature. One example is the detection of food-indnced QTc shortening (Taubel et al. 2012 Hnatkova et al. 2014). 

We noted previously that both crossover and parallel-gronp designs can be employed in TQT studies. As in any other clinical trial, the issue of statistical power is of interest. When commenting on the topic, Mayo (2009) observed as follows The... 

Even given all of these considerations, we are nonetheless left with the fundamental tenet that the TQT study employs QTc prolongation as the biomarker of proarrhythmic risk. There is widespread acknowledgement that QT interval prolongation is not the most accnrate predictor of such risk. Indeed, some researchers have commented that if it were not relatively easy to measure (at least theoretically, precise identification of the offset of the T wave can be very difficult for some waveforms), it may have been discarded aU together some time ago. 

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