With the FDA’s recent go-ahead for earlier cardiac safety testing, iCardiac Technologies has announced a risk-sharing program with sponsors that guarantees sponsors will receive precise, conclusive Thorough QT results—or pay nothing for iCardiac’s services.
Based on study size, those services can cost from $300,000 to more than $1 million, according to Alex Zapesochny, president and CEO of iCardiac Technologies, a large, dedicated electrocardiogram (ECG) core laboratory serving the pharma industry.
In cardiology, the QT interval is a measure of the time, in milliseconds, between the start of the Q wave and the end of the T wave in the heart’s electrical cycle. It represents electrical de-polarization and re-polarization of the heart’s ventricles and provides doctors with essential information: if the interval occurs in a normal amount of time or if it takes longer, based, in part, on age, sex and regularity and speed of the heart.
Long QT syndrome reflects abnormalities in the heart’s electrical recharging system. A prolonged QT interval may be due to an underlying medical condition or induced from a medication. Careful measurement of the QT interval during a clinical trial detects whether an experimental drug might prolong QT, which regulators consider an indication a drug might cause side effects such as arrhythmias or even cardiac arrest.
A review of Thorough QT studies submitted to the FDA revealed nearly one-third of those studies, conducted between 2006 and 2013, were considered either “inconclusive” or “positive” for QT prolongation, which would be a bad result. Those results often are caused by poor precision in measurement methodologies used to access the QT interval, said Zapesochny, explaining a result with no prolonged interval might actually show up as a prolonged interval—a false positive. In both cases, precision is the key.
“Since it is the ECG core lab that is in the best position to assure a highly precise study, sponsors have the right to expect the ECG core to assume responsibility for risks associated with poor precision, and we are happy to fully do so,” said Zapesochny. “Sponsors could end up needlessly discontinuing a promising drug or receiving an unfair cardiac safety warning label when poor precision is employed in a Thorough QT study.”
iCardiac’s full risk-sharing program, he said, starts with only two acceptable outcomes: the sponsor receives either a clean study without meaningful QT prolongation and the data demonstrates good assay sensitivity, or a positive prolongation result that demonstrates the drug might have a potential pro-arrhythmic effect.
“If neither of these two outcomes is achieved in our Thorough QT study, sponsors pay us nothing,” said Zapesochny.
The company also said the full risk-sharing program is applicable to studies in healthy subjects conducted at iCardiac certified sites or at sites approved by the company and executed with a written contract between iCardiac and a sponsor.
“Their ECG methodology to analyze many QT wave forms results in relatively small standard deviations, which enable increases in precision of the study,” said Philip Sager, M.D., a consulting professor of medicine at Stanford University School of Medicine and a consultant in cardiac research who has worked with iCardiac and other ECG cardiac testing laboratories. “Having high precision is important. Risk-sharing in drug development makes a lot of sense when testing variability plays an important role in the final results.”
Sager said the field is moving toward earlier QT testing during phase I, to obtain information sooner to de-risk a drug compound and save the cost and time of having to do a later Thorough QT study. High precision levels are important in performing careful QT assessments in phase I, due to the relatively small number of trial participants.
“The science is evolving,” he said, “and the company is saying it has a methodology with high precision and can guarantee the variability will be low.”
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