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Keeping Cool in the Race for Precision Medicine
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Precision medicine is rapidly racing forward and, for those of us who are watching, it may be reasonable to ask “What will this mean for me?” The most obvious question might be whether we should seek to be early adopters or lay low and wait for the dust to settle.
As former U.S. Senator Robert F. Kennedy stated in his “Ripple of Hope” speech in 1966, “There is a Chinese curse which says ‘May he live in interesting times.’” Although he was incorrect in attributing the quote to a Chinese curse, Kennedy, like British Politician Joseph Chamberlain 68 years before him, took the phrase to mean that with interesting times come not only excitement and danger but also optimism and creativity. This is the way I think of precision medicine today.
A National Research Council report on precision medicine explains that the term refers to “the tailoring of medical treatment to the individual characteristics of each patient.” Knowing this, who would not want to be all in on this concept? Fundamentally, we are still uncertain as to whether precision medicine has arrived today, will arrive in the near future, or for that matter, will arrive for our generation to incorporate into day-to-day practice. Why the uncertainty?
Cautionary Notes
I will address cautionary notes in two areas where there has been unbridled enthusiasm for precision medicine — improvement of population health and the enhancement of individual therapy selections.
Much has been said about the new federal initiative to collect data on 1 million people and to process the data in a way that helps improve health by providing predictors of disease and mechanisms to avoid such diseases. Remarkable efforts in the private sector by leading scientific visionaries, such as Leroy Hood, MD, PhD, and his P4 (predictive, preventive, personalized and participatory) initiative are attempting to define the transition from wellness to disease by studying a large population of healthy people and generating data that can be used at a personal level to prevent disease. The approach relies on generating dense, dynamic and personalized data clouds of health information. I am all for discovery, but taking a cloud of data and converting it to cures for diseases in the near future seems unlikely. Just look at all the numerous genome-wide association studies that have generated data on genetic variables in rheumatic diseases during the past decade.
From the hundreds of genes identified to associate with diseases, we now fundamentally understand the role of relatively few in disease pathogenesis and no cures are in sight. Progress is not always accelerated by big data; we have seen the remarkable Human Genome Project open more doors of questioning than it closed. I am not being a Luddite, but passionate talk, such as how we will be saved by “big data and machine learning” encourages patients to think it is easy to take control of their health.
Much has been written about the pros and cons of patients using the internet and I am all for it if it is informed. However, many patients are now encouraged to “take control” of their health by self-ordering everything from sequencing their genome to measuring their telomeric age. Analyzing your genes now seems almost “old school,” as we acutely appreciate that much of our biology is driven by epigenetic modification influenced by behavior. I am profoundly challenged to interpret such data, so I can only empathize in terms of how confusing it is for patients. While I am not paternalistic in my thinking about my patients, I am protective. How many people will make sense out of a self-ordered uric acid of 7.2 mg% ordered because their foot hurts or will be panicked by a low immunoglobin G of 676 mg% ordered because they think they have too many colds and were cruising the web? Medical scientists are now cautiously retreating in the wake of overselling. Bottom line: It may be better to not be the earliest adopter in this field and to wait for the data to speak.
Better Predictions Needed
What about the pressing need to be better able to predict the effects of our therapies? In rheumatology, this is of particular importance given the tremendous costs of our biologic treatments. Here I believe lessons can be learned from oncology where precision medicine as a modality to enhance treatment selection is increasingly incorporated into practice. The current gold standard of randomized controlled trials now has been labeled “imprecision medicine” by some, and I think it is well deserved in large part. However, up to now it has provided much benefit to medicine and has helped avoid the uninformed treatment decisions of past generations.
Fast forward to the many remarkable examples of “n of 1” therapies that have had success for seemingly refractory malignancies. Based on these examples, there is a robust initiative moving forward to exploit this design in cancer and other therapeutic areas. However, patients should understand that for now, this is not likely to provide a lottery ticket win for defeating most malignancies. Furthermore, while there are high hopes for being able to decode the complexities of the microbiome, metabolome and epigenome, to name a few of the omics, overselling to patients must be avoided. While many studies have shown hints of prediction in this field, we need larger effect sizes to make these tools standard practice.
Precision Medicine is Upon Us
As I wrote in my Editorial on biomarkers in the July 2016 issue of Healio Rheumatology, I believe precision medicine is upon us. I am enthusiastic about exploring biomarkers like the multi-biomarker disease activity score to help me appraise prognosis and sort out dilemmas in the management of patients with rheumatoid arthritis. I am also a close follower of research on the microbiome and hope this field can be reduced to some form of predicative modeling for incorporation into disease prevention, assessment and management.
Caution should not be interpreted as old thinking or thinking that is not bold. My cautions are primarily issued, first, for my patients for whom I do not want the field to oversell itself before its ready and, secondly, for my colleagues to be critical appraisers of the precision medicine tsunami that is to come.
Thank you for reading. I look forward to receiving your comments at calabrl@ccf.org or on Twitter @LCalabreseDO.
- Reference:
- Calabrese LH. Biomarkers signal the next horizon in rheumatology. Healio Rheumatology. 2016;1(5);7-8.
- For more information:
- Leonard H. Calabrese, DO, is the Chief Medical Editor, Healio Rheumatology, and Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic.
Disclosure: Calabrese reports he is a consultant for Genentech, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Jansen and AbbVie; and is on the speakers bureau for Genentech, AbbVie and Bristol-Myers Squibb and Crescendo Bioscience.