CDER Report Outlines Drug Safety Research Priorities
A new CDER drug safety report has outlined ongoing research priorities to improve drug safety. For example, one priority is to use electronic health care data to better determine suicide risks associated with approved drug products. “CDER must enhance its ability to determine if suicide is a potential adverse event of a specific drug therapy,” the report says. “However, suicidal outcomes are infrequent and difficult to measure in clinical trials. Electronic healthcare database studies can measure outcomes for large populations at lower costs than other forms of data-gathering, but their ability to accurately measure suicidal outcomes is uncertain. CDER investigators are therefore conducting a systematic review to investigate which data resources and methods have been most informative for determining suicidal outcomes in populations of interest. Available data are being assessed for their suitability to determine suicide as an outcome of drug therapy, and possibilities for enhancing future data collection on completed and attempted suicide will be explored.”
Another research priority will examine computer modeling to better predict adverse drug events. “Innovative approaches in computer science are being explored to better predict drug-related adverse reactions, by integrating medical and laboratory data with other data based on current medical knowledge and published research,” the report says. “These tools aid in understanding timing and association of drug safety signals with specific enzymes following certain anticancer treatments. As a result, investigators developed novel approaches such as machine learning and neural networks (in which computers can ‘learn’ as new data is collected) to aid regulatory agencies, industry, academia and others to understand adverse events and guide drug development and regulatory reviews.”
Another research priority will identify factors that might explain the emergence of drug safety issues in the pre- and post-market settings — and the extent to which scientific evidence, along with approaches used in precision or “personalized” medicine can be used to predict and manage safety issues, according to the report. This project will “compile a ‘catalog’ of past decisions made by CDER to place a drug approval on hold or when post-marketing safety label changes were needed. Researchers plan to map that data to possible risk management strategies, which can assist drug product reviewers and safety surveillance as well as regulatory decision-making in the postmarketing period.”
The report also details research activities under the Division of Applied Regulatory Science (DARS), where researchers are reportedly using state-of-the-art equipment and technologies in areas such as toxicology, pharmacology, biophysics, chemistry, genomics, and computational modeling that will be used in developing new and innovative approaches to improve CDER’s drug product review capabilities. DARS scientists are currently involved in over 30 projects that advance drug development and safety assessments. For example, DARS uses a number of laboratory and computer-based approaches to measure the impact of specific sets of drugs on heart function. “These combined approaches will allow better prediction of both the functional effects and scope of injury associated with cardiotoxic drugs, thereby enhancing the safer use of medications,” the report says.
And another DARS effort to investigate drug-induced cardiac toxicity sees the Division working as part of a research consortium to evaluate the possibility of predicting drug-induced cardiac toxicity using a computer model of the human ventricular cell. “This project involves evaluating drugs and then simulating their effects on electrical activity in the heart under a wide range of conditions,” the report says. “The study seeks to develop a new regulatory pathway that will change current cardiovascular safety testing guidelines and potentially eliminate the need for certain kinds of clinical testing during drug development,” it says.