The Genome on Drugs
Howard McLeod, PharmD, likes to have fun, though his definition of “fun” might not be what you’d expect. True, he enjoys playing sports with his kids and jamming on his electric guitar. But he also loves doing research on pharmacogenomics and negotiating with insurance companies to provide this new type of testing. Whereas others might find work to be, well, work, McLeod describes his job as director of the Institute for Pharmacogenomics and Individualized Therapy (IPIT) like a man who just won the lottery.
Howard McLeod, PharmD, likes to have fun, though his definition of “fun” might not be what you’d expect. True, he enjoys playing sports with his kids and jamming on his electric guitar. But he also loves doing research on pharmacogenomics and negotiating with insurance companies to provide this new type of testing. Whereas others might find work to be, well, work, McLeod describes his job as director of the Institute for Pharmacogenomics and Individualized Therapy (IPIT) like a man who just won the lottery.
“Getting paid to answer the most clinically relevant questions is an amazing example of luck,” said McLeod. “To me, it is not just about doing research, but doing impactful research and trying to make sure that when you go home, you feel like the time you spent has not just been career prolongation but has driven the field forward.”
McLeod originally wanted to do clinical work, but began to change his mind when he volunteered as a student for a research study. The trial was testing an over-the-counter version of the antacid Zantac, and he was struck by how enthusiastic the lead scientist was to get the results. But what really sealed the deal was the time he spent, after getting his PharmD, doing postdoctoral fellowships at St. Jude’s Children’s Hospital in Memphis and the Beatson Institute in Glasgow, Scotland.
“As I dug into the clinical research I realized that the people who were leading the clinical research were having even more fun than those doing clinical practice,” said McLeod. “There were times where they were pulling their hair, but for the most part they were enjoying themselves and also having an impact on hundreds and sometimes thousands of people.”
With his background in pharmacy, McLeod was keenly interested in why different people respond in completely different ways to the exact same drug. For instance, some people might have a dramatic lowering of blood pressure, while some people’s blood pressure might actually go up. Some people might get a rash; some people might not. His research has focused on explaining this variation in response to medicines and then applying that at the regulatory level with drug labels, at the practitioners’ level to get the tests ordered in the clinic, and at the insurance company level to get them reimbursed. That’s a lot for just one investigator to tackle, so when he was asked five years ago to come to UNC to direct an entire institute focused on those same goals, he eagerly accepted.
“The whole idea behind IPIT was to take on all of the stumbling blocks that are truly holding up personalized medicine, whether it is the need for more genetic information, the lack of a device, or the informatics shortfalls, and bring together different types of people to tackle each of them in a cohesive manner,” said McLeod.
The institute celebrates all it has accomplished over the last five years with a symposium September 19. For example, researchers at IPIT have helped to move genomic tests into clinical trials quicker than ever before. They extended little known information that genetic variation in the gene CYP2D6 could indicate what dose of the chemotherapeutic drug tamoxifen will be most effective in treating breast cancer patients. Once they had built up enough data in the laboratory they decided to test the concept in a patient population, and ended up enrolling 500 patients in about a year when they had expected to only enroll about 20 per year. The study, which had an initial report in the August 20 issue of the Journal of Clinical Oncology, had statewide impact, including patients from 64 of the 100 North Carolina counties. The researchers are hoping to be as successful as they apply similar tactics to a variety of other diseases, including heart disease and mental illness.
Key to this effort is the Novel Methodology core, which Howard McLeod helps to lead within the North Carolina Translational and Clinical Sciences (NC TraCS) Institute. NC TraCS is UNC’s home of the NIH Clinical and Translational Science Awards (CTSA), a national consortium created to turn discoveries into practical solutions for patients. Through the Novel Methodology Core, director of the molecular genetics laboratory Karen Weck, M.D., Ph.D., has helped investigators turn their pre-clinical research into clinical-grade assays that are safe enough to use in patients.
Last year, doctors at UNC-Chapel Hill ordered over 1000 pharmacogenomic tests in a variety of areas, such as infectious diseases, cardiology, and oncology. Though some clinicians are still a bit reticent to use genetics, many have accepted it as one of the many tools to help them manage their patients better. McLeod has developed a number of smart phone applications – such as iwarfarin, an app for calculating the dose for the popular blood thinner warfarin -- to guide practitioners as they use these new pharmacogenomic tests in their practice.
Not satisfied with just educating scientists and physicians about the merits of pharmacogenomics, McLeod has also begun talking with insurance companies about how the new tests can improve health care. Through a rather unconventional approach, he has let the payers pick the endpoints of the research. As a result, the researchers have changed their measure of success from things like an academic data point or a paper in The New England Journal of Medicine to other metrics, like reduced doctor’s visits or fewer prescriptions. If the researchers don’t meet the new endpoint, they move on. But if they are successful, then insurance companies have to pay up. As McLeod describes it, the process is much more painful at the start, but moves the research that much closer to the clinic where it can have an actual impact.
That impact is what makes research fun to McLeod, who credits NC TraCS and endeavors like it with motivating investigators to take their work to the next level. He laughs when he remarks that he is no longer interested in science that just interests him – it has to be entirely translational in nature.
“There are a lot of people who think they are doing translational research, but all they are doing is making the first step of it,” said McLeod. “This idea that one would build one quarter of a bridge across a river and think that they’re done is just insane. Either we have a plan to build the whole bridge or we don’t do it at all. If we are going to do translational research in its fullest, we need to be good at the hand-off at all of the different stages, not just at the early stage.”
