Testing people to understand more about their genetic information isn’t a new practice, but it's part of a rapidly-changing pharmacology field. The second phase of NIH-funded network, “Implementing Genomics in Practice (IGNITE),” is underway at five locations across the country, including IU School of Medicine. Todd Skaar, PhD, and Paul Dexter, MD, are the principal investigators of the IU site. Skaar is also the leader of the IU Grand Challenge Precision Health Initiative Pharmacogenomics Program. Skaar says his main focus is to understand how someone's genetic variability contributes to the way they respond to drugs, which involves pharmacokinetics – what our bodies do to the drugs – and pharmacodynamics – what drugs do to our body. Researchers on his team can test patients to see if they have specific genetic variants, which may affect the way their enzymes activate or inactivate certain drugs.
"If you give hundreds of people the same dose of a drug, the levels of the drug in the blood can vary about tenfold," said Skaar. "That's just because of the way each person's body gets rid of the drugs. A lot of that is our liver, our kidneys and whether it gets absorbed."
Because of those differences, Skaar says certain people may be more likely to get side effects from a particular drug, or not get the full efficacy of a different drug, because of their genetic makeup. Researchers at Skaar’s lab have been studying about a dozen genetic variants for the last five years, learning about the way they interact with patients who take medicine for heart attacks (Plavix), organ transplants (Tacrolimus or Azathioprine) or oncology treatments (Capecitabine or Fluorouracil).
"What we’re working on doing is coming up with a mechanism to return these results directly to the patient in a format they can either make sense out of or give it to their provider, so they can have it wherever they are," said Skaar. "The ultimate goal is to have the information on a card that would have a QR code and it would link to updated recommendations, such as, 'based on this genotype, we have these recommendations.' We need to understand what the patients want, what information we think is clinically important and how to convey that information in a way that's understandable to the patients and that they will use it in a safe and effective way, rather than either to not understand it and throw it away or do things they shouldn't do.”
Skaar says the cards would be about the size of an insurance card, small enough for patients to keep in their wallet for easy access. Another one of Skaar's goals is to incorporate that genetic information into each person’s medical record at hospitals across the country. One of the challenges with a project of this scope is that different healthcare providers use different kinds of software for medical record information, so Skaar's team is starting by developing a way to incorporate it into Cerner software, currently used by IU Health. Skaar says this is not a simple task, but they're trying to keep the momentum of their progress moving in the right direction.
"We can’t just sit back and wait for someone else to do it," said Skaar. "Now that we’ve got that started, it's taking a while, but we've got all the agreements and approvals to do it and it's starting to move forward."
As genetic testing technology advances, Skaar says it will be important for physicians, pharmacists and other medical professionals to take additional classes in continuing education so they will know how to incorporate it. Skaar says he sees the value in these developments for patients as well as providers.
"It will help them make choices," said Skaar. "For example, there are a variety of antidepressants now and oftentimes they will just try one and if that doesn't work, they'll try another one. Then patients have to come back. It [a genetic test] is not going to get them the right one the first time without questions, but it should reduce the amount of times they have to change medication. It should get them closer to the right one and the right dose to start with."
As part of IGNITE II, Skaar's team is also getting ready to start two big clinical studies. The first is a pharmacogenetics study (ADOPT-PGx: A Depression and Opioid Pragmatic Trial in Pharmacogenomics) where patients get their genetic information tested and doctors use what they learn to guide therapy, either for opioid-based treatments (for chronic or acute pain) or patients on antidepressants. Skaar is the principal investigator of the ADOPT-PGx study.
The second is a study for patients who have hypertension (GUARDD-US: Genetic testing to Understand Renal Disease Disparities across the U.S.), some who get genetic information tested and others who do not, to see whether they are more likely to progress to chronic kidney disease if they know about relevant genetic information. Michael Eadon, MD, is the principal investigator of the GUARDD-US study.
Both of the NIH-funded studies are set to begin in 2020 and will include about 2,000 people at IU Health or Eskenazi Health, plus others across the country.