March 26, 2018
“The central precept of my life is that every meeting, every phone call, every email I answer in relation to work, should be followed with a question to myself: ‘Did what I do just now improve the health and well-being of children?’ Because if it didn’t, then I’m not focused on the right thing.
~ Dr. Bruce Carleton
Dr. Bruce Carleton’s research is centered on drug therapy with the goal of improving human health and quality of life. For nearly three decades, he has focused on developing models to evaluate drug effectiveness, medication use models designed to improve patient health, and effective surveillance systems for the safe use of medication. He is particularly interested in pediatric medicine, with specific emphasis on the epidemiology and clinical management of adverse drug reactions.
Bruce and his team were recently awarded funding through two major Genome Canada competitions — the Large Scale Applied Research Program (LSARP) for Genomics and Precision Health, where his Go-PGx (Pharmacogenomics) project aims to prevent chemotherapy side effects in children, and the Genomics Applications Partnership Program (GAPP) where he will work to integrate pediatric pharmacogenomic testing into the Canadian health care system in partnership with Dynacare, one of the largest laboratory services provider in Canada.
When he started the Pharmaceutical Outcomes and Policy Innovations program (POPi), to better understand prescription drug outcomes and the variability between patients in experiencing both positive and harmful outcomes from drugs, genomics was not as accessible and affordable as it is today. Pharmacogenomics has become an important tool for clinicians to help patients achieve better outcomes — and better patient outcomes must remain the primary focus.
While his innovative research and work on policy development have made him one of Canada’s leading experts in adverse drug reactions, his belief of serving the patient is equally inspiring. He credits his father for teaching him that, “to be fully human and fully alive, you have to be engaged in your community.” This has been his guidepost throughout his career as he works to achieve better health outcomes through the translation of pharmacogenomic research into clinical applications.
Bruce recently sat down with Genome BC to share his insights about the evolution of pharmacogenomics in the clinical health care setting.
Genome BC (GBC): What was the impetus for your interest in drug research and pharmacogenomics?
I had asked myself, “What great problems with drug therapy exist that have not yet been solved?” And one of the questions was, “Why do some people experience tragic side effects and others don’t?” And “Is anybody doing something about that?” I realized that this presented a great opportunity.
Ninety-five per cent of adverse drug reactions are never reported to federal regulators. The whole idea of voluntary surveillance and expecting busy clinicians to report the necessary information about an adverse event in detail seemed silly. So, I’ve spent a lot of years looking at how we could improve reporting and most importantly, what to do with the reported information to improve patient outcomes.
I was searching for a technology that could help me understand the variability between people who got a drug, at this dose, with these disease states, and had an adverse reaction compared to somebody who was in exactly the same circumstances, but didn’t have the reaction. And in the early 2000s it began to look like genomic technology was cost-effective enough that we would be able to use it in that capacity.
I began reading medical genetics literature of the day, which was making broad leaps about how this was going to personalize therapy. I knew it was going to be more complicated than was suggested. However, it was interesting and the technology allowed me to begin thinking about how to put the idea of side-effect surveillance and rigorous data collection together with a new technology to be able to come up with a plan.
GBC: How would you describe the benefits pharmacogenomics provides for patients?
Bruce: Our healthcare system is complex and still too often reflects a provider centric focus versus a patient care focus. So, precision medicine and pharmacogenomics can be a way for patients to say, “I want to understand the likely benefit to me, as well as the likely harm to me, so I can make a more informed decision.”
We know there can be individual variability in our response to drug treatment — the same treatment doesn’t always work in patients with similar conditions. The problem I have is that some patients might actually be harmed by a drug meaning that they’re now in hospital battling an adverse reaction instead of at home with their families.
Pharmacogenomics straddles the line. It doesn’t identify ‘bad drug’ versus ‘good drug’ for patients. It helps to identify the ‘right drug’ and ‘wrong drug’ for each patient. It identifies for whom a drug is likely to be effective or for whom a drug is likely to be harmful. Both outcomes of drug therapy are important to create a patient-specific benefit-risk profile that patients and clinicians together can use to make better drug therapy decisions.
GBC: Where does the science of pharmacogenomics need to go next?
Bruce: We’ve been working on specific adverse drug reactions, for specific drugs. For these drugs, we know there is significant variation in adverse drug reactions. Understanding that variability helps us to make smarter choices. Now we are studying what to do with that information. Perhaps use a lower dose, or use something else. That’s where the science is at.
We don’t know the genomic risk and benefit of every drug. There are thresholds of evidence we must have in order to make sense of all genetic variation and that’s going to take some time. So, where I think the science needs to go in the short-term, is to understand genetic variation across an increasing number of patients, and how relevant these variations are to individual patients in the circumstances in which they’re using the drug.
Ideally, I think we should sequence everyone’s DNA and have everyone’s information available for clinicians to use in treatment. And as we meet thresholds of evidence for genetic data, we move that patient’s genetic information from the library of sequenced data into the patient’s medical record so it can be accessible to clinicians. That might be the most efficient way to get important treatment related information to patients and their clinicians.
GBC: Genome BC hosted a series of talks on adverse drug reactions. There was discussion about pharmacogenomics in the community pharmacy, which provides a report to patients and their health care professional. What are your thoughts to this approach?
Bruce: I believe pharmacogenomics has to be coupled with the drug use process. So, the physician prescribes a drug and the patient takes the prescription to the pharmacist who dispenses the medication. The patient is told by their pharmacist and doctor what they can expect and is asked to report any adverse effects. This process, however, is strictly linear and shifts responsibility to the patient.
Pharmacogenomics can provide the patient with information about their likelihood of a response. The process only becomes circular when the physician receives data that can be acted upon and incorporated into prescribing decision-making. Therefore, the physician should order the pharmacogenomics test, and know how to utilize the results. Certainly, pharmacists can help here too.
GBC: So, you believe the process would be more effective when the physician orders the test?
Bruce: I believe the process must be circular. It makes sense for pharmacists to handle the logistics of DNA collection, but when you start providing interpretation of reports at the counter, and there are 30 patients lined up get their prescriptions, how much time does the pharmacist really have?
It can be just as challenging for physicians. At the end of the day, you still have a report that needs interpretation. Physicians and pharmacists, in general have limited genomic knowledge or are not properly set up to provide that service. That’s still going to be a challenge.
GBC: What can be done to overcome that challenge and help educate health care providers?
Bruce: Health care providers can learn about the use and benefits of genomics, but we don’t have to teach them everything there is to know about human genetics. What they need to understand is how to utilize the information that is provided. For example, physicians should know why a drug should be avoided and what alternative should be used. If a dose reduction is warranted, then they will need to know how much of a reduction and over what period of time. These are just some of the important pieces of information that need to be conveyed in health care provider education.
GBC: How does the approach you’re taking through your GAPP project tackle these challenges?
Bruce: I spend a lot of time making recommendations to physician colleagues, helping them come up with therapeutic plans for patients, so I know the kind of information they find useful.
First we tested our pharmacogenomics reports to ensure we were providing the kind of information physicians can use, but ultimately I want to solve that individual patient problem for the physician. Physicians really want to talk with somebody to help ensure that they’re making the right decisions for their patient. That’s the piece that I’ve coupled with this — a 1-800 number to get someone from my team on the phone where they can have a conversation about what might be unclear or not specific enough to be useful in a report of genetic test results.
The problem is time. Physicians have less time with a patient than they would ultimately like. You have to provide them with support. You can’t just provide reports and education sessions and expect them to be comfortable. Doctors don’t prescribe genes, they prescribe drugs. You can’t tell them “*2*2 variant.” You have to tell them what that means in terms of treatment options. Physicians know therapeutic plans carry risk, but also a benefit. Physicians need better information on the degree of risk, not just whether the patient is “at risk.”
We have set up physician, pharmacist and patient focus groups to test this at children’s hospitals across the country. For example, at Children’s Hospital of Eastern Ontario where I have clinical pharmacists working with physicians. We’ll figure out the amount of education they need, and how to provide them the supplemental help as pharmacogenomic results are known. This information will help us roll out testing in other institutions over time.
GBC: So, you believe that more one-on-one support is needed for physicians to help them deliver better outcomes for patients through pharmacogenomics.
Bruce: Yes. I’m not just interested in providing genetic information online. I’m interested in serving the patient. And if I am serving the patient, then I must serve the physician and pharmacists, too.
