|This month we return to our interviews, and hear from Professor William Clarke, Chair of the TDM in Oncology committee. Alongside academic and clinical work, Professor Clarke is involved in an academic initiative in disposable microfluidic diagnostics, which has potential to impact the clinical application of TDM in resource limited settings.
Associate Professor, Pathology
Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Can you tell us a little bit about your respective roles? What is a typical day like for you?
I am an Associate Professor of Pathology in the School of Medicine, and Director of Clinical Toxicology and Point-of-Care Testing for the Hospital. I also oversee a clinical mass spectrometry research lab, and I’m involved in a large microfluidics/nanotechnology initiative at the University. No day is ever the same for me, which is something that I love. I am able to contribute to patient care, be involved in interesting research initiatives, and mentor students and trainees every day.
Is there anything that your laboratory does, or that is done at your hospital/centre, that you would consider innovative?
In our mass spectrometry lab, we are applying this technology to facilitate novel tissue analyses that can be used clinically as well has high-throughput screening and quantitative methods. In our microfluidics lab, we are developing low-cost diagnostic technologies that can be used to increase access in developing countries and other resource limited settings.
What technological innovations have entered into use during your career that have permitted a change, or evolution, in practice?
Over the course of my career, the use of mass spectrometry in the clinical lab has increased dramatically. It is still used for only a small percentage of tests performed in a Core Laboratory, however it is no longer just accessible in large, academic medical centers. This has impacted practice significantly, as clinical labs are able to routinely support pain management physicians with detailed analyses, and also increases access to TDM of drugs for which there is no commercial assay.
How did you become interested in your area of expertise?
During my graduate work, we developed chromatographic immunoassays for free drugs and hormones, which stirred my interest in thinking about how drug measurements could be used for treatment of patients, but I wasn’t clear on how I could get involved in that type of work. I was fortunate that during my Clinical Chemistry training at Johns Hopkins, the American Association for Clinical Chemistry (AACC) held a series of TDM Renaissance meetings in Baltimore. I attended the first meeting to learn more about the field, and was lucky that our colleagues such as Chuck Pippenger, Steve Wong, and Catherine Hammett-Stabler were so willing to reach out and get a young person like myself involved. Through those meetings in Baltimore, and subsequent IATDMCT meetings, I was hooked and I have never looked back.
Is there anything that you’ve seen or heard about recently and thought “I’d like to incorporate that idea at my center”?
I’m fascinated at the thought of the lab taking a more active/collaborative role in drug management through tools such as the ISBA from Professor Marquet’s laboratory. Combining this type of analysis with automation through software development to create a tool that our pharmacists and physicians can use for their day-to-day patient care activities is something that really excites me. However, in our institution there are a lot of challenges to get the information needed for this analysis, so we have a way to go.
What sort of research do you have on the horizon that you think might influence clinical practice in the future?
I think that it’s hard to predict what research will impact practice in the future, but the project we’re working on that has the most potential is the development of disposable microfluidic diagnostics. This is a competitive field, so it may be someone else’s design that is adopted, but making testing more accessible (when needed) could really impact clinical practice in resource limited settings.
What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?
From a technology standpoint, I think it is difficult to envision a future without mass spectrometry being central to laboratories supporting TDM and CT. As the field moves forward rapidly, I think that affinity-based technologies such as immunoassays require far too long to develop useful assays, and MS also affords the ability to measure the parent drug and important metabolites in a single analysis – important for both TDM and CT. From an applications standpoint, I think that TDM of oncology, psychoactive, and anti-infective drugs are where there are great opportunities for TDM to make an impact. In CT, untargeted screening coupled with targeted analysis as follow-up seems to be an approach that will allow us to adequately support clinicians and adapt to the ever-changing usage patterns and emerging substances of abuse. The biggest challenge we face is the lack of understanding of the value of our field to patient care – we have to demonstrate that we provide a clinical service, and not just a commodity (i.e. a numeric result). I am actually excited to see the response of our discipline to this challenge. There is so much creative work going on to show the clinical impact of TDM and CT by both established and young scientists in the field. I am also excited to see the technological advances that will enable that creativity for years to come.
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