The Grand Challenges Annual Meeting, hosted by the Bill & Melinda Gates Foundation and Grand Challenges Canada among others, aims to address urgent global health problems by bringing researchers with a global health passion together.
Professor Andrea Edginton was invited to participate on a panel discussing the use of physiologically based pharmacokinetics (PBPK) models for drug development in global health. With the meeting overlapping the 10th Annual World Health Summit, keynote speakers included Bill Gates and German Chancellor Angela Merkel.
Edginton’s research focuses on building virtual people in computers and assessing how drug pharmacokinetics changes with, for example, age or disease. Pharmacokinetics is a field that uses mathematics to describe a drug’s absorption, distribution, metabolism, and excretion from the body. By harnessing information from large populations of patients, virtual people can be used to test why patients differ in pharmacokinetics and how this might change the drug dose each patient needs to ensure effective treatment. Edginton’s speciality is building virtual children to assess how dosing may change as the child grows and matures. This information is useful for planning pediatric clinical trials where getting the dose right is of utmost importance.
Edington’s research has been recognized with over two million dollars of funding from various funding agencies in the last year. Here are some of the projects this funding supports:
Medication use in breastfeeding women
When breastfeeding, women are often advised to avoid taking certain medications or to stop breastfeeding if on certain drugs. Though appropriate at times, there are many situations when this advice is not directly supported by evidence; instead, physicians exercise caution because for many drugs there is no data on how much of that drug is excreted into breastmilk. To avoid potential dangerous effects on breastfeeding infants, women are thus advised to avoid either the medication or the act of breastfeeding.
In partnership with SickKids Hospital in Toronto, Edginton is conducting research that will fill this gap. Her partners at SickKids collect breastmilk from mothers on common drugs that women may be taking prior to or post-childbirth. The breastmilk is analyzed to determine what concentration of the medication is in the milk. Edginton then uses large data sets to create PBPK models of virtual infants: she inputs the data gathered by the team into these models and assesses how much exposure the infants will have to the drug during breastfeeding. These exposures would be difficult to gather directly from infants as many blood samples would be necessary. With the computer model however, she can estimate exposure which informs the risk assessment process.
Once they have perfected their methods, the researchers plan to assess the top five drugs used by women pre- and post-birth for which there is no safety data. This work is funded by the Canadian Institute of Health Research (CIHR).
Developing an open source tool to get generic drugs to market faster
Brand name versus generic drugs: the price is different, but the drug has the same effect. This is because generic drug companies spend significant time and resources developing a product that is bioequivalent to the brand version. Bioequivalence means that the two drug products exhibit the same pharmacokinetic profile when taken and therefore should act the same in the body.
Demonstrating bioequivalence is complex, and Edginton’s team, from the Children’s Hospital of Los Angeles and Bayer, is developing a tool that will allow generic drug companies and regulators to simulate the probability of a successful bioequivalence trial. This tool will enable companies to refine their trial designs and get generic drugs to market faster.
The online platform for running these simulations is entirely open source, meaning it is available free of charge around the world. Edginton and her collaborators have received funding from the United States Food & Drug Administration to continue to develop the tool.
Evaluating the effectiveness of an online platform for hemophilia dosing
The Web Accessible Population Pharmacokinetic Service – Hemophilia (WAPPS-Hemo) is an online platform to help clinicians determine safe drug doses for patients with hemophilia. WAPPS-Hemo was initiated at McMaster and developed in collaboration with Edginton and her lab group.
Hemophilia is a rare bleeding disorder where a person’s blood does not clot normally. Patients often take medication every few days to treat this chronic condition but determining how much medication to take is challenging since patients vary greatly in their pharmacokinetics and thus in their effective doses. WAPPS-Hemo houses the largest collection of pharmacokinetic information on people with hemophilia and has over 330 participating hemophilia treatment centres in over 30 countries. This research database of real-world information has the potential to transform hemophilia care and, with funding from the Canadian Institutes of Health Research, Edginton and collaborators will be assessing the effectiveness of the service.
Dr. Edginton’s work and the impressive funding it has received demonstrates the vital role pharmacokinetics plays in improving medication safety, particularly in populations where running clinical trials is challenging and existing safety data is limited.