In 2007, I was asked to chair the AACC’s Personalized Medicine Advisory Task Force. It was our job to advise the AACC on matters related to personalized medicine. The first thing we needed was a definition of “personalized medicine.” After substantial deliberations we agreed that personalized medicine is the integration and application of an individual’s unique healthcare information to predict, prevent, diagnose and treat disease. This is differentiated from traditional medical practice, which is supported by population-based information.
I think it helps to think not of “personalized” medicine, but of “precision” medicine. It’s a way of helping physicians identify the most effective means of treating an individual patient – to, in effect, increase the precision of their ordered therapy.
The practice of laboratory medicine is central to personalized medicine. We’re on the cusp of major disruptions based on our understanding of the molecular and genetic legions underlying pathophysiologic processes. While everyone agrees that molecular knowledge will sharpen the ability of physicians to target the very specific needs of individual patients, we don’t often discuss how the development of precise, personal therapies makes laboratories key architects of healthcare practices.
I highly recommend "The Innovators Prescription: A Disruptive Solution to Healthcare" by Clayton M. Christensen, Jerome H. Grossman, and Jason Hwang. The book outlines how centrally important our profession is to the future of medicine. I have a few questions based on that insightful text that may help us chart our own path to the future of medical care:
1) Will diagnostics trump therapeutics? For years pharmaceuticals have dominated medical therapeutics. As we learn more about how individuals respond differently to medicines, we’re heading in a direction where physicians won’t prescribe certain drugs until some type of biochemical analysis shows the drug will be effective on that specific patient. My lab PGXL, has physician clients that use CYP2C19 tests with every Plavix prescription, making sure Plavix is the correct choice. That’s going to be more and more common as the diagnostic information provided by laboratories drives the use of pharmaceutical agents.
2) Will pathologies be defined by the “state” of a molecular pathway? In The Innovator’s Prescription, the authors believe that diseases will be increasingly categorized by their molecular characteristics. Patients may be diagnosed as having a Jak-2 or a KRAS or a p53 disease. These diagnoses would provide a biochemically targeted therapeutic regimen. Hence, we see the evolving role of laboratory medicine: providing both the definitive diagnosis and the optimal therapeutic. The concept of a “companion diagnostic” is already being embraced by both pharmaceutical manufacturers and regulators. It is an approach by which the practice of laboratory medicine rises to a higher level in the healthcare hierarchy.
3) Will we (once again) rethink the concept of normality? The use of “average” dosing schema is rapidly fading, and the new standard of practice is based on biochemically-defined subgroups in which “average” has an entirely new meaning. This doesn’t challenge the use of reference range as a concept; it enhances it by identifying narrower reference ranges that can inform the physician’s treatment decision. For example, in warfarin therapy it is now accepted that genotyping can stratify individuals into three different groups, each of which requires a different “average” dosing strategy.
4) Should clinical trials be used as “discovery” experiments? Most clinical trials define a “normal” group compared to a group with a known pathology. Then, on average, the treatment works marginally. Might this be an opportunity to explore whether the initial diagnosis of the supposedly diseased group was really accurate? We need new approaches to define patient subgroups and look for characteristics not understood in their initial selection.
Maybe, after the same initial diagnosis, some had a different disease or a molecular legion not responsive to the therapy. Laboratories need to be involved in those clinical trials at a sufficiently early stage to define the relevant molecular characteristics that sets the subjects apart.
These are only a few of the questions the coming disruption poses for laboratory medicine. I really believe that the answers to these and other questions will define our profession for years to come. As we discuss scientific advances and the very real needs of our healthcare system to adapt and adopt, the bottom line – now more than ever – is that we are central players and recognized enablers of the disruption that is taking place.