Getting the values right: Which QT correction formula is most accurate in healthy volunteers?

Prolonged QT intervals on an electrocardiogram (ECG) can signal increased risk of life-threatening arrhythmias, including Torsades de Pointes and sudden cardiac death. Yet the QT interval is highly dependent on heart rate. As the heart beats faster, the interval shortens; as it slows, the interval lengthens. To make results comparable, clinicians and researchers correct the QT interval to what it would be at 60 beats per minute, known as QTc.

Correcting the QT interval, however, is not straightforward. Different formulas exist, each with strengths and limitations related to how they account for heart rate differences across age, sex, and BMI. Choosing the most appropriate one for the population and context is crucial, as an inaccurate correction may either overstate risk or miss clinically significant prolongation. Four popular formulas are used today: Bazett’s, Fridericia’s, Framingham’s and Hodges’.

ICON and our partners at the University Medical Center Groningen, Netherlands, recently compared these four formulas to determine which provides the most reliable correction in healthy individuals, where accuracy is essential both for patient care and for the integrity of clinical trial data. We jointly published a paper with the findings, entitled A comparison of the four most commonly used formulae to adjust the QT-interval for heart rate in 22,000 healthy subjects, and share the conclusions in this blog.

The challenge of QT correction

Until now, no study has looked at QT correction in such a large group of healthy people or examined in detail how age, BMI and different heart rate groups might affect the accuracy of different formulas. This study helps fill that gap by comparing the most widely used methods in both the overall population and in subgroups.

Bazett’s formula has been the standard for more than a century and is still recommended by the European Society of Cardiology. However, it often overestimates at fast heart rates and underestimates at slow ones, which can cause confusion. Other formulas, including Fridericia’s, Framingham’s and Hodges’, were created to address these issues. Each applies a different mathematical approach to adjusting for heart rate variation, and evidence has suggested that some may perform better in specific clinical or research settings.

A study in healthy volunteers

Previous comparisons of QT correction methods have often been based on patient populations, where underlying conditions and treatments complicate the evaluation. By focusing on healthy individuals, this study could assess formula performance in a more stable context, providing insights that are highly relevant for both preventive medicine and early-phase research.

The large-scale analysis conducted at ICON’s early phase unit in Groningen included healthy volunteers who ranged widely in age, sex and body mass index (BMI) to gain deeper insights into formula performance across these key subgroups. Researchers retrospectively examined ECGs from 22,063 healthy volunteers, collected under tightly controlled resting conditions between 1997 and 2023. The Pearson correlation coefficient (r) between QTc and heart rate (HR) and the linear regression slope (b) were calculated for each formula and the influence of age, sex body mass index and heart rate.

16,170
males
5,893
females
34.9
mean age
24.2
mean BMI

Key findings

The analysis revealed clear differences between the formulas:

Fridericia’s formula was the most accurate overall. It showed the least dependency on heart rate, producing consistent results across sexes, age groups, BMI categories and heart rate ranges.
Framingham’s formula performed best in very low BMI participants, although this group made up less than 1% of the population studied.
Hodges’ formula demonstrated moderate accuracy, but with more variability than Fridericia’s.
Bazett’s formula performed the poorest, with substantial over- and under-estimation depending on the heart rate.

The findings support what many researchers and regulators have already observed in practice: while Bazett’s formula has been most commonplace, it may not be the most appropriate tool for all cases of modern clinical decision-making. This is supported by the FDA’s recommendations for Fridericia’s formula and the increasingly common use of Fridericia’s within the pharmaceutical industry in general.

The nuance behind QTc formula choice

It is important to stress that no single formula is perfect. The accuracy of QT correction can vary depending on patient characteristics and clinical context. For example, some pediatric studies suggest Bazett’s formula may still be useful in neonates, while in oncology trials it has often exaggerated QT prolongation, potentially excluding patients unnecessarily.

This nuance highlights why formula choice should never be automatic. Instead, it requires careful consideration of the population being assessed and the potential consequences of misclassification. For clinicians, the risk lies in either withholding a beneficial treatment or exposing a patient to avoidable danger. For researchers, the stakes involve trial safety and the viability of promising new therapies.

Implications for practice and research

Our study’s findings align with regulatory trends. In pharmaceutical research, Fridericia’s formula is already widely used and is endorsed by ICH E14 guidance as the preferred option in most circumstances. Clinicians, however, often continue to apply Bazett’s, partly for consistency with historical data.

Greater alignment between clinical and research practice could reduce confusion and ensure that patients receive the safest and most effective care. It would also provide clearer data for regulators evaluating new medicines.

Looking ahead

Although Fridericia’s formula emerges as the most reliable in healthy adults, new approaches are being developed. For example, the QTcAd formula, which incorporates demographic factors like age. These may provide further refinements and help tailor QT correction more precisely to individual patients.

BMI as a subgroup in this study is an important inclusion. As noted above, the study found that Fridericia’s formula performed more accurately with all BMI ranges except the very lowest (underweight), where Framingham’s performed best. For BMI ranges encompassing healthy, overweight, and obese categories, Fridericia’s formula is superior. With the global rise in obesity research and the rapid growth of cardiometabolic and obesity-related clinical trials, understanding how BMI influences QT correction is increasingly important. Reliable formula choice ensures that safety assessments in these studies reflect true cardiac risk.

Conclusion

QT correction is both essential and complex. This study of more than 22,000 healthy volunteers confirms that Fridericia’s formula provides the most accurate correction across a broad range of individuals. However, nuance is always at play as formula choice should always reflect the population and context at hand.

By adopting a more considered approach to QT correction, clinicians and researchers can avoid misinterpretation, protect patient safety and strengthen the evidence base for new therapies. Learn more about the nuances of formula performance and selection by reading the full published study.

Hoek LJ, Voors AA, Maass AH, Riesebos M, Brouwer JL. A comparison of the four most commonly used formulae to adjust the QT-interval for heart rate in 22,000 healthy subjects. J Electrocardiol. 2025;92:154091. doi:10.1016/j.jelectrocard.2025.154091.