By: Marsha B. Henderson, MCRP
FDA research has been especially important in helping FDA better understand cardiovascular diseases in women and the effects of drugs on women’s heart health.
Knowing that heart disease is the leading cause of death for women, our Office of Women’s Health (OWH) has been committed to using a significant portion of our limited funds to support cardiovascular research from the very beginning of our research program in 1995. We’ve accomplished that by working across several FDA Centers to support studies on issues ranging from sex differences in cardiac interventions to the cardiotoxicity of breast cancer drugs.
One of our earliest funded projects examined the connection between certain drugs and Torsade de Pointes (TdP) – a rare but dangerous heart arrhythmia that can lead to sudden death. Women are more likely than men to have this heart rhythm problem. FDA has been leading an effort to evaluate better ways to screen drugs for their potential to cause this rhythm problem. This is made possible in part because drugs that cause TdP almost always prolong the QT-interval on the electrocardiogram (ECG), which measures the heart’s electrical cycle.
On the heels of Heart Health Month, I wanted to highlight the history of FDA research on QT prolongation and demonstrate the ways ongoing collaborations across FDA research programs are helping to advance policies and projects to protect women’s heart health.
Early Years: Understanding the Sex Differences
The exact reason for the higher rate of drug-induced TdP in women is unknown. OWH funded studies to help FDA better understand the mechanism of the sex differences in drug-induced QT prolongation. OWH also funded research within the Center for Drug Evaluation and Research (CDER) enabling post-market drug analysis to better recognize drug safety effects in women.
Supporting the Development of FDA Guidance
Building on the previous studies, OWH partially funded additional research on metabolic drug-drug interactions that contribute to QT prolongation. This research contributed to FDA guidance on the assessment of the QT prolongation potential of drugs for both men and women. As part of this guidance, FDA recommended that drug sponsors conduct a comprehensive study, called the Thorough-QT (TQT) study when seeking FDA approval of a new drug. The TQT study, implemented in 2005, has been an effective screening tool. Although certain commonly used drugs, such as antihistamines and antibiotics, had to be withdrawn from the US market because of drug-induced QT prolongation concerns, no such withdrawals have been necessary since 2005.
Moving Forward: Improving Prediction and Prevention
Although the current FDA guidelines are very useful for identifying QT prolonging drugs, not all QT prolonging drugs cause TdP. OWH is currently partnering with CDER to sponsor studies to better screen for the subset of QT-prolonging drugs that have lower or no risks for TdP. This new research has the potential to enhance drug development and safety for both women and men by improving the accuracy of the evaluation of a drug’s potential to cause heart rhythm problems, and by providing this information earlier in drug development.
Marsha B. Henderson, MCRP, is FDA’s Assistant Commissioner for Women’s Health