Mapping the drivers of overdiagnosis to potential solutions
BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3879 (Published 16 August 2017) Cite this as: BMJ 2017;358:j3879
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As a GP concerned to limit the growth of medicalisation and ‘healthism’(1), I welcome Pathirana et al’s account of some of the ways this might be achieved. But I take issue with two points in their opening paragraph. First, while ‘a growing body of evidence’ indicates that diagnosis and treatment can both cause harm, no amount of evidence can tell us how much is ‘too much’ medicine this is a value judgement. Second, any intervention offered to a person who feels well at present relates to a health problem that may ‘never cause them harm’. Screening tests particularly often involve ‘“the detection of abnormalities that are not destined to ever bother” most of us. Implying that any individual can be ‘overdiagnosed’ makes no sense without a crystal ball. In the thyroid cancer example presented, what we need to know is how many lives were lengthened for every 100,000 people diagnosed and treated. Once available, this information will inform a value judgement about the number of people who should suffer diagnosis and treatment in return for one life lengthened. This value judgement can be made by health economists who calculate which interventions are cost effective, or by individuals who evaluate the pros and cons of an intervention they are offered. The challenge for clinicians is to help people do this evaluating in the consulting room.
While accepting Pathirana et al’s recommendation that campaigns should challenge the public’s current beliefs about how much medicine is just right, I should like the overdiagnosis conversation to accept that it is not doctors’ job to specify this ‘right’ amount. Also, the assumption that the public believe ‘more is better’ is open to challenge. My own research (2) suggests that in accounting for their everyday decisions about preventive medication, patients negotiate the tension between ‘medical progress’ and ‘medicalisation’. I see less evidence that the biomedical community has yet engaged with this tension, but am encouraged that a forthcoming RCGP meeting focuses on both over- and under-treatment. Such engagement is urgently needed as genetic screening begins to generate an enormous number of new ‘at risk’ labels, a juggernaut that needs to be guided by people who simultaneously fear medicalisation and welcome medical progress.
1. Crawford R. Healthism and the medicalization of everyday life. International Journal of Health Services. 1980;10(3):365-8.
2. Polak L. What is wrong with ‘being a pill-taker’? The special case of statins. Sociology of Health and Illness. 2017;39(4):599–613.
Competing interests: No competing interests
The Journal must be commended for its crusade against overdiagnosis: the first mention was in 1984.(1) The term has appeared in 217 articles including two recent ones: an analysis in the “too much medicine” section and an essay looking for solutions.(2,3) Sadly, this may be whistling in the wind.
First, the problem is not about “too much medicine” but simply about bad medicine.
Second, the term “malpractice” was never used once in these two articles.(2) To prescribe a risky procedure when there is no potential benefit is an error! This error has complex roots but the cornerstone is innumeracy.(4) Adding to it illiteracy is just flying in the face of the sad evidence to duck one's responsibilities.
Last, malpractice, as Janus, has two faces: Overuse and underuse. For the latter one example could be enough: only one-half of patients with cancer who smoke are counselled to quit although cessation is an important factor in the outcome (treatment effectiveness, overall survival, risk of second primary malignancies, quality of life).(5)
Could our system be more frequently the hall of shame than of fame than we believe? To hijack a quote from Séguéla, a French publicist, about his job: “Do not tell my mother that I am a healthcare professional, she believes me pianist in a brothel”.
1 Alm J, Hagenfeldt L, Larsson A, Lundberg K. Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis. BMJ 1984;289:1171-5.
2 Pathirana T, Clark C, Moynihan R. Mapping the drivers of overdiagnosis to potential solutions. BMJ 2017; 358: j3879.
3 Carter SM. Overdiagnosis, ethics, and trolley problems: why factors other than outcomes matter—an essay by Stacy Carter. BMJ 2017; 358: j3872.
4 Braillon A. Discrepant expectations about benefits and harms: innumeracy plus illiteracy? JAMA Intern Med 2017;177:1225-1226.
5 Ramaswamy AT, Toll BA, Chagpar AB, Judson BL. Smoking, cessation, and cessation counseling in patients with cancer: A population-based analysis. Cancer 2016 15;122:1247-53.
Competing interests: No competing interests
References to H L's rapid response of 21 August 2017 with links that work:
1. Llewelyn H. Reducing over -diagnosis and over-treatment by improving their criteria and stratifying them. Preventing Overdiagnosis Conference, Oxford, 2014, poster 34. http://www.preventingoverdiagnosis.net/2014presentations/Board%2034_Huw%...
2. Llewelyn H, Ang AH, Lewis K, Abdullah A. The Oxford Handbook of Clinical Diagnosis, 3rd edition. Oxford University Press, Oxford, 2014, pp 615 – 664. http://oxfordmedicine.com/view/10.1093/med/9780199679867.001.0001/med-97...
Competing interests: No competing interests
The problem is that EBM as currently promulgated does not include the tools to find the solutions to over-diagnosis. EBM is in reality evidence based screening (supported by sensitivity and specificity) and efficacy (supported by RCTs). There is far more to medicine than screening and efficacy.
RCTs are not used currently to identify who benefits and to what extent. Sensitivity and specificity are used to assess non-numerical screening tests and to place cut-offs for numerical tests. They do not help to assess tests for use in differential diagnosis, diagnostic criteria and or offering treatments to patients to consider, which is why we have over-diagnosis and over-treatment.
One example of how to assess tests in order to avoid over-diagnosis was described in an over-diagnosis conference some years ago by stratifying patients within an RCT [1]. However, there seems to have been little interest in solutions until now. If we wish to apply such solutions, we need doctors and other health professionals who are familiar with the thought processes of day to day patient care who are also mathematicians and statisticians. This approach is now being taught to students [2].
It is not only the public, industry and health professionals who need a change of culture and education. There is a need for those who do research and promulgate EBM to expand their skills and horizons in order that they can help to provide solutions to current problems.
References
1. Llewelyn H. Reducing over -diagnosis and over-treatment by improving their criteria and stratifying them. Preventing Overdiagnosis Conference, Oxford, 2014, poster 34. http://www.preventingoverdiagnosis.net/2014presentations/Board%2034_Huw%...
2. Llewelyn H, Ang AH, Lewis K, Abdullah A. The Oxford Handbook of Clinical Diagnosis, 3rd edition. Oxford University Press, Oxford, 2014, pp 615 – 664. http://oxfordmedicine.com/view/10.1093/med/9780199679867.001.0001/med-97...
Competing interests: No competing interests
Re: Mapping the drivers of overdiagnosis to potential solutions: Is the UK ready for an Imaging Biomarker Solution to the Breast Screening Debate?
Thanya Pathirana's article beautifully explains the current problem of "Too much medicine", but in our necessary attempts at de-escalation we must be careful not to throw the baby out with the bath water. Within health screening in particular we must sort out our tool kit and use diagnostic devices that find significant disease, early discovery of which is truly beneficial to the population.
The NHS Breast Screening Programme was set up in 1988. Its rigorous quality assurance surpasses that of other areas of radiology and of medicine. Nevertheless, overdiagnosis is a reality (1,2), and we must also ask why, when we know that finding breast cancer early saves lives (3), is breast cancer still the second commonest cause of oncological mortality for women in the UK?
The explanation for both overdiagnosis and underdiagnosis lies in the diversity of breast cancer biology, improved understanding of which has revolutionised breast cancer treatment and greatly improved survival. An era of personalised cancer therapy has begun, that depended on the revelation that breast cancer is not one disease (4). Breast cancer subtypes demonstrate a vast heterogeneity in presentation, biology, risk of progression, response to treatment and survival outcomes.
Digital mammography is an effective diagnostic tool for breast cancer, but it is best at picking up less aggressive cancers that distort the structure of the breast as they grow or engender calcium deposition. More aggressive, faster growing cancers often replace the surrounding breast tissue without distortion, and can remain undetected mammographically until they are large enough to be felt clinically (5).
Host-related factors also affect the visibility of cancer on mammograms. The density of breast cancer tissue tends to be similar to that of normal glandular breast parenchyma, and therefore, if breasts are predominantly glandular, a cancer is more likely to remain invisible within this tissue mammographically. This variable is known as breast density. At age 50, 50% women have breasts dense enough to obscure a small cancer (6), introducing an unspoken inequality of effectiveness of mammographic screening programmes worldwide.
Targeted breast cancer treatments, developed over the past few decades, depend for their effectiveness on the use of biomarkers to identify particular molecular characteristics and allow treatments tailored to the individual cancer (7). These biomarkers are measured from samples obtained at biopsy or surgery, and are therefore inherently invasive. Imaging biomarkers (IB) are inherently non-invasive and could potentially enable screening targeted to biologically aggressive cancers.
Functional Magnetic Resonance Imaging (MRI) is being evaluated but is not yet included in clinical practice. However, dynamic contrast-enhanced (DCE) MRI is our current standard screening test for young women at high risk of breast cancer (>30% lifetime risk) and demonstrates features associated with biological aggression in breast cancer (8). The trouble with MRI is the high cost of equipment, compounded by long acquisition and interpretation times, making it unsuitable for use in a wider screening population. It remains reserved for those at highest risk despite increasing evidence that it could also benefit average risk women by enabling diagnosis of the aggressive cancers underdiagnosed by mammography (9).
There is now increasing interest worldwide in abbreviated breast MRI. This was first described using the acronym FAST MRI in 2014 and takes far less time to acquire and report than the full-protocol breast MRI (10). Early results imply that this technique could provide a cost-effective screening tool for a wider group of women (11). FAST MRI is best at picking up cancers that are biologically aggressive because it retains elements of the DCE protocol that demonstrate cancer perfusion and enhancement morphology.
Abbreviated MRI holds great promise as an imaging biomarker in a screening application, but large scale studies are necessary to test it rigorously, in terms of effectiveness, patient acceptability and cost, against our standard screening modalities, to ensure that it truly can reduce both overdiagnosis and underdiagnosis. The EA1141 study has recently begun recruiting in USA to compare abbreviated MRI with digital breast tomosynthesis (the most advanced radiographic breast imaging method) for women with dense breasts (12). Since tomosynthesis is still undergoing evaluation itself (13), comparison of FAST MRI with digital mammography would be a more appropriate study for the UK. Mammography is an effective test for most women of screening age, and it may be that the future of effective screening, like that of effective treatment, for breast cancer, lies with a tailored approach for each individual.
The solution to overdiagnosis and underdiagnosis is not to undermine our national breast screening programme that cost-effectively provides quality-assured, standardised population screening (14), but instead to enable high quality research to guide the evolution of that screening programme into a new imaging biomarker age.
References:
1. Gemma Jacklyn, Paul Glasziou, Petra Macaskill and Alexandra Barratt Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography. British Journal of Cancer (2016) 114, 1269–1276. doi:10.1038/bjc.2016.90
2. Pathirana T, Clark J and Moynihan R. Mapping the drivers of overdiagnosis to potential solutions. BMJ 2017; 358: j3879 doi: 10.1136/bmj.j3879
3. Saadatmand S, Bretveld R, Siesling S et al. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173797 patients. BMJ 2015;351: h4901
4. Curtis C, Shah SP, Chin S-F, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, METABRIC Group, Langerod A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Borrensen-Dale A-L, Brenton JD, Tavare S, Caldas C and Aparicio S. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012; 486: 346-352
5. Sung JS, Stamler S, Brooks J, Huang T, Dershaw DD, Lee CH, Morris EA and Cornstock CE. Breast cancers detected by screening MR imaging and mammography in patients at high risk: Method of detection reflects tumor histopathologic results. Radiology 2016; 280: 716-722
6. American College of Radiologists publication; BI-RADS Atlas 5th edition 2013: ISBN No: 9781559030168 (Breast Composition Categorisation) p123-132
7. Duffy MJ, Harbeck N, Nap M, Molina R, Nicolini A, Senkus E and Cardoso F. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). European Journal of Cancer 2017; 75: 284-298
8. Yamamoto S, Han W, Kim Y, Du L, Jamshidi N, Huang D, Kim JH and Kuo MD. Breast Cancer: Radiogenomic biomarker reveals associations among dynamic contrast-enhanced MR Imaging long noncoding RNA and metastasis. Radiology 2015;275: 384-92
9. Kuhl CK, Strobel K, Bieling H, Leutner C, Schild HH, Schrading S. Supplemental Breast MR Imaging Screening of Women with Average Risk of Breast Cancer. Radiology. 2017 May;283(2):361-370
10. Kuhl CK, Schrading S, Strobel K, Schild HH, Hilgers R-D and Bieling HB. Journal of Clinical Oncology 2014;32: 2304-2310
11. Chlor CM and Mercado CL Abbreviated MRI Protocols: Wave of the Future for Breast Cancer Screening. American Journal of Radiology 2017; 208: 284-289
12. Kuhl C. Invited commentary: Abbreviated breast MRI for screening women with dense breast: The EA1141 Trial. British Journal of Radiology 2017 epublished ahead of print
https://doi.org/10.1259/bjr.20170441
13. Gilbert FJ, Tucker L, Gillan MG, Willsher P , Cooke J, Duncan KA, Michell MJ, Dobson HM, Lim YY, Purushothaman H, Strudley C, Astley SM, Morrish O, Yooung KC and Duffy SW. Health Technology Assessment 2015;19::i-xxv, 1-136. The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme – a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone
14. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG and Wilcox M - The Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. British Journal of Cancer 2013; 108: 2205-2240
Competing interests: No competing interests