Margaret McCartney: Are we too captivated by precision medicine?
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j1168 (Published 09 March 2017) Cite this as: BMJ 2017;356:j1168All rapid responses
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Health and sickness are like the two ends of a seesaw. As one goes up, the other goes down. So health spares us from swings and slides of sickness and merry-go-rounds of misguided, dizzy doctors, who think that health is merely the absence of sickness. But health is more than the absence of sickness, just as life is more than the absence of death. Health is the shield between life and death.
Competing interests: No competing interests
Health is homeostasis. Homeostasis is an internal feedback system that stabilizes and balances our body's chemistry, so that our organs work smoothly and efficiently with each other. Sickness is the disruption of homeostasis, which doctors treat with medicine. But medicine adjusts one homeostatic mechanism by disrupting another, which leads to more sickness and more medicine. This is why medicines are so profitable, but have so many side effects and adverse reactions. So healthcare should minimize medicine and maximize holistic factors, such as lifestyle, diet, exercise, education, recreation, and relationships.
Competing interests: No competing interests
I think that 'precision medicine' is an admirable objective, which can (I hope) be summed-up as 'offered treatment which is tailored to the biological-individuality of the specific patient', and I do of course agree with Dr McCartney that the point of a trial, is to obtain its results.
Reordering a few of Dr McCartney's sentences:
'Personalised medicine is definitely the goal, but technology may not always be needed to obtain it. We could use a bit more personalised medicine and precision right now; it doesn’t need a genome, and it doesn’t need much technology. The tool is talking—having conversations to decide what interventions are wanted and warranted.'
I have just ended a response about CPR (ref 1) on the same theme:
'... the only satisfactory resolution, is to ‘have held the necessary ‘consent discussions’’ in advance of the cardiopulmonary arrest.'
Competing interests: No competing interests
Medicine is the ultimate personalised technology
The power of modern medicine is that it combines science with the art of communicating and caring for individual patients. Talking with patients and their families to identify the best clinical management has always been central to what we do whether in primary, secondary or tertiary care and whether at the start or the end of life, in the acute or the chronic setting.
The fact that medicine is as much a science as an art in the 21st century is thanks to tremendous technological advances. In the past many of our tools have been rather blunt and often we have had to resort to algorithms that have a “one size fits all” approach. Powerful imaging and genomic sequencing technologies, to name but two examples, mean that we can be much more precise in understanding the disease and deciding on a treatment. For example, we can precisely treat infections that are resistant to first line antibiotics not by trial and error or from long-waiting for rounds of culture and sensitivity results but in a timely fashion through sequencing the bacterial DNA (e.g. [1]). In cancer the ability to “look inside” a patient’s tumour and characterise it as a molecular level is already leading to less toxic therapies and advances in survival and quality of life for some patients (e.g. in melanoma [2]).
It goes without saying that this more complex array of diagnostic tests and treatments leads to more responsibility on clinicians to understand the options and explain them to our patients. In her article Margaret McCartney highlights the concerning finding that doctors overestimate the benefits and underestimate the harms of interventions. As options become more individualised, doctors should perhaps be encouraged to “use more science” in their art of communicating and understanding the risks and benefits. This might include tools to assess and navigate existing evidence as well as to communicate them fairly [3]. We are in a fantastic era of big data, genomes and population studies – those of us deeply involved with the science and the trials are also tackling these challenges and performing the critical analyses.
McCartney chose Cytosponge as an example of short-cuts to implement technology. Cytosponge is an example of a technology that has the possibility to bring diagnosis of patients with reflux symptoms into the primary care setting. Furthermore, because the cells collected by the simple patient-friendly device are coupled with molecular assays is has the potential to risk stratify patients at risk for cancer of the oesophagus - which is a lethal disease (http://www.bbc.co.uk/programmes/p04wtqpp). There are no short-cuts to clinical implementation and this diagnostic test is progressing through carefully designed clinical trials spanning over 10 years which encompass measures of acceptability, accuracy and health economics [4-8]. The BEST3 trial will involve 9,000 patients across the UK (http://www.wolfson.qmul.ac.uk/current-projects/best3). Too often there is a delay between academic-led clinical trials and implementation in the health service. As Catapult put in their statement assistance will be provided so that the Cytosponge is ready to be adopted into clinical practice following completion of the BEST3 trial.” McCartney then asks, “Shouldn’t we wait for the results of this large trial first?” This is baffling since of course the results of the BEST3 trial will be peer reviewed, and only if successful will the Cytosponge be adopted into clinical practice.
Precision medicine per se is not a recipe for “false alarms and poor sensitivity”. It is the imprecise use of novel diagnostics that carry such risks. Application of precision medicine to early diagnosis focusses on increasing both sensitivity and specificity and thereby not only increasing the benefits, but also reducing the harms of early diagnosis. For example, work on molecular biomarkers in patients with Barrett’s oesophagus will identify a small sub-group for whom treatment is most likely to be beneficial and a large majority for whom risk of progression to cancer is very small. Technology offers real potential for improving the quality as well as the quantity of life.
Let’s embrace all that new technology can offer – medicine has always been in the business of offering a customised approach for our patients and the newly coined term “precision” or “personalised” medicine reflects the fact that our scientific armamentarium is starting to catch up with the art of individual care for patients.
References
1. Raven KE, Reuter S, Gouliouris T, et al. Genome-based characterization of hospital-adapted Enterococcus faecalis lineages. Nature microbiology 2016;1(3) doi: 10.1038/nmicrobiol.2015.33[published Online First: Epub Date]|.
2. Holderfield M, Deuker MM, McCormick F, et al. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nature reviews Cancer 2014;14(7):455-67 doi: 10.1038/nrc3760[published Online First: Epub Date]|.
3. Hoffman TC, Montori VM and Mar CD The Connection between evidence-based medicine and shared-decision making JAMA 204;(13)1295-1296
4. Lao-Sirieix P, Boussioutas A, Kadri SR, et al. Non-endoscopic screening biomarkers for Barrett's oesophagus: from microarray analysis to the clinic. Gut 2009;58(11):1451-9 doi: 10.1136/gut.2009.180281[published Online First: Epub Date]
5. Kadri SR, Lao-Sirieix P, O'Donovan M, et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study. Bmj 2010;341:c4372 doi: 10.1136/bmj.c4372[published Online First: Epub Date]|
6. Weaver JM, Ross-Innes CS, Shannon N, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nature genetics 2014;46(8):837-43 doi: 10.1038/ng.3013[published Online First: Epub Date]|.
7. Ross-Innes CS, Becq J, Warren A, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma. Nature genetics 2015;47(9):1038-46 doi: 10.1038/ng.3357[published Online First: Epub Date]|.
8. Ross-Innes CS, Debiram-Beecham I, O'Donovan M, et al. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study. PLoS medicine 2015;12(1):e1001780 doi: 10.1371/journal.pmed.1001780[published Online First: Epub Date]|.
Competing interests: RCF is named on patents pertaining to the Cytopsonge and associated assays that have been licensed by the Medical Research Council to Covidien (now Medtronic) RCF and PS are Chief Investigators on the BEST3 Grant PS has been on scientific advisory boards for companies that are interested in molecular diagnostics PS is director of a CTU some of whose trials are in the area of stratified medicine (in rheumatoid arthritis)