Preventing overdiagnosis: How to stop harming the healthy

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MEDICALISATION
Preventing overdiagnosis: how to stop harming the
healthy
Evidence is mounting that medicine is harming healthy people through ever earlier detection and
ever wider definition of disease.With the announcement of an international conference to improve
understanding of the problem of overdiagnosis, Ray Moynihan, Jenny Doust, and David Henry
examine its causes and explore solutions
Ray Moynihan senior research fellow
1
, Jenny Doust professor of clinical epidemiology
2
, David
Henry chief executive officer
3
1
Bond University, Robina, Queensland, Australia;
2
Centre for Research in Evidence-Based Practice, Faculty of Health Sciences and Medicine, Bond
University, Australia;
3
Institute for Clinical Evaluative Sciences, Toronto, Canada
Medicine’s much hailed ability to help the sick is fast being
challenged by its propensity to harm the healthy. A burgeoning
scientific literature is fuelling public concerns that too many
people are being overdosed,
1
overtreated,
2
and overdiagnosed.
3
Screening programmes are detecting early cancers that will
never cause symptoms or death,
4
sensitive diagnostic
technologies identify “abnormalities” so tiny they will remain
benign,
5
while widening disease definitions mean people at ever
lower risks receive permanent medical labels and lifelong
treatments that will fail to benefit many of them.
3 6
With
estimates that more than $200bn (£128bn; €160bn) may be
wasted on unnecessary treatment every year in the United
States,
7
the cumulative burden from overdiagnosis poses a
significant threat to human health.
Narrowly defined, overdiagnosis occurs when people without
symptoms are diagnosed with a disease that ultimately will not
cause them to experience symptoms or early death.
3
More
broadly defined, overdiagnosis refers to the related problems
of overmedicalisation and subsequent overtreatment, diagnosis
creep, shifting thresholds, and disease mongering, all processes
helping to reclassify healthy people with mild problems or at
low risk as sick.
8
The downsides of overdiagnosis include the negative effects of
unnecessary labelling, the harms of unneeded tests and therapies,
and the opportunity cost of wasted resources that could be better
used to treat or prevent genuine illness. The challenge is to
articulate the nature and extent of the problem more widely,
identify the patterns and drivers, and develop a suite of responses
from the clinical to the cultural.
At the clinical level, a key aim is to better discriminate between
benign “abnormalities” and those that will go on to cause harm.
In terms of education and raising awareness among both the
public and professionals, more honest information is needed
about the risk of overdiagnosis, particularly related to screening.
More deeply, mounting evidence that we’re harming healthy
people may force a questioning of our faith in ever-earlier
detection, a renewal of the process of disease definition, and a
fundamental shift in the systemic incentives driving dangerous
excess.
Next year, an international scientific conference called
Preventing Overdiagnosis aims to deepen understanding and
awareness of the problem and its prevention. The conference
will take place on 10-12 September 2013 in the United States,
hosted by the Dartmouth Institute for Health Policy and Clinical
Practice in partnership with the BMJ, the leading US consumer
organisation Consumer Reports, and Bond University. The
conference is timely, as growing concern about overdiagnosis
is giving way to concerted action. The Archives of Internal
Medicine’s feature “Less is More” now regularly augments the
evidence base,
9
high level health policy groups in Europe are
debating ways to tackle excess,
10
and the recently launched
Choosing Wisely campaign warns about dozens of potentially
unnecessary tests and treatments across nine specialties.
11
Many factors—including the best of intentions—are driving
overdiagnosis, but a key contributor is advances in technology.
The literature suggests several broad and related pathways to
overdiagnosis: screening detected overdiagnosis in people
without symptoms; overdiagnosis resulting from use of
increasingly sensitive tests in those with symptoms;
Correspondence to: R Moynihan raymoynihan@bond.edu.au
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Feature
FEATURE

overdiagnosis made incidentally—“incidentalomas”; and
overdiagnosis resulting from excessively widened disease
definitions. These different pathways are not mutually exclusive,
and a more rigorous classification of the different forms of
overdiagnosis will be a focus of discussion at the 2013 scientific
conference.
Screening detected overdiagnosis
This pathway to overdiagnosis occurs when a screening
programme detects disease in a person without symptoms but
the disease is in a form that will never cause that person
symptoms or early death. Sometimes this form of disease is
called pseudodisease. Contrary to popular notions that cancers
are universally harmful and ultimately fatal, some cancers can
regress, fail to progress, or grow so slowly that they will not
cause harm before the individual dies from other causes.
5
As
we will discuss below, there is now strong evidence from
randomised trials and other studies comparing screened and
unscreened populations that an important proportion of the
cancer detected through some popular screening programmes
may be pseudodisease.
4 12
Evidence from autopsy studies
suggests a large reservoir of subclinical disease in the general
population, including prostate, breast, and thyroid cancer, the
bulk of which will never harm.
12
Similarly, screening the hearts
of people without symptoms or at low risk may also lead to
overdiagnosis of coronary atherosclerosis and subsequent
unnecessary interventions.
13
Our understanding of the nature
and extent of overdiagnosis and the amount of pseudodisease
detected by screening remains limited but is evolving, and as
Woolfe and Harris observed recently in JAMA, “concern about
overdiagnosis is justified.”
14
Increasingly sensitive tests
People presenting to doctors with symptoms can also be
overdiagnosed because changes in diagnostic technologies or
methods have enabled the identification of less severe forms of
diseases or disorders. It is becoming clearer that a substantial
proportion of these earlier “abnormalities” will never progress,
raising awkward questions about exactly when to use diagnostic
labels and therapeutic approaches traditionally deployed against
much more serious forms of disease.
Incidentalomas
Diagnostic scanning of the abdomen, pelvis, chest, head, and
neck can reveal “incidental findings” in up to 40% of individuals
being tested for other reasons.
15
Some of these are tumours, and
most of these “incidentalomas” are benign. A very small number
of people will benefit from early detection of an incidental
malignant tumour, while others will suffer the anxiety and
adverse effects of further investigation and treatment of an
“abnormality” that would never have harmed them. As others
have shown, the rapidly rising incidence for some cancers, set
against relatively stable death rates, is a phenomenon suggestive
of widespread overdiagnosis, whether from screening or the
detection of incidentalomas (figure⇓).
12
Excessively widened definitions
Another pathway to overdiagnosis is through disease boundaries
being widened and treatment thresholds lowered to a point where
a medical label and subsequent therapy may cause people more
harm than good. Changing diagnostic criteria for many
conditions are routinely increasing the numbers of people
defined as sick,
16
causing virtually the entire older adult
population to be classified as having at least one chronic
condition.
17
This widening has happened both with asymptomatic
conditions that carry a risk of an adverse event, such as
osteoporosis, where treatments may do more harm than good
for those at very low risk of fracture,
18
and for behavioural
conditions such as female sexual dysfunction, where common
difficulties have been reclassified as dysfunctions.
19
Such changes in diagnostic criteria are commonly made by
panels of health professionals with financial ties to companies
that benefit directly from any expansion of the patient pool.
20
As definitions broaden and thresholds fall, people with smaller
risks or milder problems are labelled, which means the potential
benefits of treatment decline, raising the possibility that harms
will outweigh benefits. As Welch and colleagues estimated in
their 2011 book Overdiagnosed,
3
many people diagnosed and
treated long term for near-normal cholesterol concentration or
near-normal osteoporosis may be “overdiagnosed,” in the sense
that they would never have experienced the events their
treatments are designed to prevent.
A related form of overdiagnosis occurs when people are
diagnosed outside of already widened diagnostic criteria, as can
occur when inappropriate manufacturers’ norms exaggerate the
incidence of abnormality,
21
when diagnostic methods wrongly
label random or normal fluctuations in biomarkers as true
abnormalities,
22
or when important qualifiers are left out of the
process of diagnosis.
23
Examples of overdiagnosis
The growing evidence on overdiagnosis suggests the problem
may exist to varying extents across many conditions (box 1),
including those for which underdiagnosis may simultaneously
be a feature. For some conditions, the evidence remains tentative
and speculative, for others it has become much more robust.
Breast cancer
Arguably the strongest evidence of overdiagnosis comes from
studies of screening detected breast cancers, though estimates
of its extent are wide ranging. A 2007 systematic review in
Lancet Oncology found the proportion of overdiagnosis of
invasive breast cancer among women in their 50s ranged from
1.7% to 54%.
24
An Australian study estimated the rate was at
least 30%,
25
while a Norwegian study calculated 15-25%.
26
A
2009 systematic review in the BMJ concluded up to one third
of all screening detected cancers may be overdiagnosed.
4
However, even with strong evidence from population based
studies, it is currently impossible to discriminate between
cancers that will harm and those that will not.
Thyroid cancer
While the chances of tests detecting a thyroid “abnormality”
are high, the risk it will ever cause harm is low.
3 27
Analysis of
rising incidence shows many of the newly diagnosed thyroid
cancers are the smaller and less aggressive forms not requiring
treatment,
28
which itself carries the risk of damaged nerves and
long term medication.
3
Gestational diabetes
A 2010 revision of the criteria defining gestational diabetes
recommended a dramatic lowering of the diagnostic threshold,
more than doubling the number of pregnant woman classified
to almost 18%.
29
Proponents argue universal screening with the
new definition will reduce health problems, including babies
being “large for gestational age.”
29
Critics, however, are calling
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BMJ 2012;344:e3502 doi: 10.1136/bmj.e3502 (Published 29 May 2012) Page 2 of 6
FEATURE

Box 1: Problems of overdiagnosis
Asthma—Canadian study suggests 30% of people with diagnosis may not have asthma, and 66% of those may not require medications
37
Attention deficit hyperactivity disorder—Widened definitions have led to concerns about overdiagnosis; boys born at the end of the
school year have 30% higher chance of diagnosis and 40% higher chance of medication than those born at the beginning of the year
46
Breast cancer—Systematic review suggests up to a third of screening detected cancers may be overdiagnosed
4
Chronic kidney disease—Controversial definition classifies 1 in 10 as having disease; concerns about overdiagnosis of many elderly
people
23
Gestational diabetes—Expanded definition classifies almost 1 in 5 pregnant women
31
High blood pressure—Systematic review suggests possibility of substantial overdiagnosis
22
High cholesterol—Estimates that up to 80% of people with near normal cholesterol treated for life may be overdiagnosed
3
Lung cancer—25% or more of screening detected lung cancers may be overdiagnosed
56
Osteoporosis—Expanded definitions may mean many treated low risk women experience net harm
18
Prostate cancer—Risk that a cancer detected by prostate specific antigen testing is overdiagnosed may be over 60%
12
Pulmonary embolism—Increased diagnostic sensitivity leads to detection of small emboli. Many may not require anticoagulant treatment
39
Thyroid cancer—Much of the observed increase in incidence may be overdiagnosis
28
for an urgent debate before the new expanded definition is more
widely adopted, because they fear many women may be
overmedicalised and overdiagnosed, that the screening test has
poor reproducibility for mild cases, the evidence of benefit for
the newly diagnosed pregnant women is weak, and the benefit
modest at best.
30 31
Chronic kidney disease
More than 10% of adults in the United States are now classified
as having some form of chronic kidney disease.
32
A working
definition launched as part of new clinical guidelines
33
asserts
that an estimated glomerular filtration rate (eGFR) below 60
ml/min/1.73m
2
and sustained for three months or longer is
deemed abnormal, a decision critics argue automatically creates
the potential for overdiagnosis, particularly among elderly
people.
34
According to Winearls and Glassock in an article last year the
new classification system is “like a fishing trawler” and
“captures many more innocent subjects than it should.”
23
They
estimate that up to one third of people over 65 may meet the
new criteria, yet of these, fewer than 1 in 1000 will develop end
stage renal disease each year. They also point to major problems
with the reliability and consistency of the eGFR test and express
concern many older people are being labelled on the basis of a
single and potentially inaccurate laboratory measure. Elsewhere
they have argued that “the majority of those held to have CKD
[chronic kidney disease] have no identifiable kidney disease”
and they’ve highlighted attempts by some organisations to move
away from the controversial new definition, raise the threshold
for diagnosis, and dramatically reduce prevalence.
35
Responding
to criticisms, proponents have defended the new definition as
being “clear, simple, and useful.”
36
Asthma
Although asthma can be severe and may be underdiagnosed and
undertreated, some studies suggest that there may also be
substantial overdiagnosis. One large study in 2008 found that
almost 30% of people diagnosed as having asthma did not have
the condition, and almost 66% of those did not need drugs or
asthma care during six months of follow-up.
37
The authors
concluded, “A substantial proportion of people . . . may be
overdiagnosed with asthma and may be prescribed asthma
medications unnecessarily.” In the same year a Dutch study
found that of 1100 patients using inhaled corticosteroids, 30%
may have been using the drugs without any clear indications.
38
Pulmonary embolism
Doctors think of pulmonary embolism as a “not to be missed”
diagnosis, because failure to detect it can have catastrophic
consequences. Historically it was diagnosed only when the
blockage was large enough to cause infarction of part of the
lung or haemodynamic instability. In such patients, treatment
with an anticoagulant or a thrombolytic agent was considered
mandatory. Now, however, computed tomography (CT)
pulmonary angiography can detect smaller clots, and there is
uncertainty about whether treatment is always necessary.
39
Analysing trends before and after the widespread introduction
of CT pulmonary angiography, Weiner and colleagues suggested
that the almost doubling in incidence “reflects an epidemic of
diagnostic testing that has created overdiagnosis,” with much
of the increase consisting of “clinically unimportant” cases that
“would not have been fatal even if left undiagnosed and
untreated.”
40
An observational study is investigating the safety
of not treating people with very small blood clots.
41
Attention deficit hyperactivity disorder
Much has been written about expanding diagnostic definitions
within mental illness and concerns about the dangers of
overtreatment.
42
Debate has intensified with suggestions that
current processes for defining disease may be contributing to
the widespread overdiagnosis of conditions such as bipolar,
autistic disorder, and attention deficit hyperactivity disorders.
43 44
One focus of concern is the possible overdiagnosis of children,
who have no say in the appropriateness of a label that can
permanently change their lives. This is particularly salient with
attention deficit hyperactivity disorder.
45
A recent study of
almost a million Canadian children found boys born in
December (typically the youngest in their year) had a 30%
higher chance of diagnosis and 40% higher chance of receiving
medication than those born in January, with the authors
concluding their findings “raise concerns about the potential
harms of overdiagnosis and overprescribing.”
46
Drivers of overdiagnosis
The forces driving overdiagnosis are embedded deep within the
culture of medicine and wider society, underscoring the
challenges facing any attempt to combat them (box 2). A key
driver is technological change itself. As Black described in
1998, the ability to detect smaller abnormalities axiomatically
tends to increase the prevalence of any given disease.
5
In turn
this leads to overestimation of the benefits of therapies, as milder
forms of the disease are treated and improvements in health are
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FEATURE

wrongly ascribed to treatment success, creating a “false
feedback” loop fuelling a “cycle of increasing testing and
treatment, which may eventually cause more harm than benefit.”
5
The industries that benefit from expanded markets for tests and
treatments hold widereaching influence within the medical
profession and wider society, through financial ties with
professional and patient groups and funding of
direct-to-consumer advertising, research foundations, disease
awareness campaigns, and medical education.
8
Most importantly,
the members of panels that write disease definitions or treatment
thresholds often have financial ties to companies that stand to
gain from expanded markets.
20
Similarly, health professionals
and their associations may have an interest in maximising the
patient pool within their specialty, and self-referrals by clinicians
to diagnostic or therapeutic technologies in which they have a
commercial interest may also drive unnecessary diagnosis.
Avoidance of litigation and the psychology of regret is another
obvious driver as professionals can be punished for missing the
early signs of disease yet don’t generally face sanctions for
overdiagnosing. Quality measures focused on doing more may
also encourage overdiagnosis in order to meet targets for
remuneration incentives.
47
An intuitive belief in early detection, fed by deep faith in
medical technology is arguably at the heart of the problem of
overdiagnosis. Increasingly we’ve come to regard simply being
“at risk” of future disease as being a disease in its own right.
Starting with treatment of high blood pressure in the middle of
the 20th century,
48
increasing proportions of the healthy
population have been medicalised and medicated for growing
numbers of symptomless conditions, based solely on their
estimated risk of future events. Although the approach has
reduced suffering and extended life for many, for those
overdiagnosed it has needlessly turned the experience of life
into a tangled web of chronic conditions. The cultural norm that
“more is better” is confirmed by recent evidence suggesting
patient satisfaction flows from increased access to tests and
treatments, even though more care may be associated with
greater harm.
49 50
What can we do about overdiagnosis?
Building on existing knowledge and activity, the 2013
conference on overdiagnosis will provide a forum for learning
more, increasing awareness, and developing ways to prevent
the problem (www.preventingoverdiagnosis.net). Research on
overdiagnosis is now recognised as part of the future scientific
direction of the National Cancer Institute’s division of cancer
prevention in the United States.
51
The 2013 conference hopes
to provide researchers working in this field with the chance to
share and debate methods and further advance research agendas.
As to education, the development of a range of curriculums and
information packages could help raise awareness about the risks
of overdiagnosis, particularly associated with screening.
52
In
association with the BMJ, a series of articles about the potential
for overdiagnosis within specific conditions is being planned.
And at the level of clinical practice new protocols are being
developed to bring more caution in treating incidentalomas.
3
Similarly, some are urging that we consider raising the
thresholds that define “abnormal”—in breast cancer screening,
for example—and evaluate methods of observing changes to
some suspected pathologies over time, rather than intervening
immediately.
53
As we’ve seen, early studies of how to safely
undiagnose or de-prescribe are starting to emerge.
At a policy level, reform of the process of defining disease is
urgently required, with one model coming from the National
Institutes of Health in the United States, where people with
financial or reputational conflicts of interest are disqualified
from panel membership.
20
Dispassionate assessment of evidence
may result in disease definitions being narrowed, as has been
seen with the recent tentative proposals to raise thresholds for
high blood pressure that could demedicalise up to 100 million
people.
54
Processes for defining disease may also benefit from
an attempt to synthesise the evidence from clinical medicine
with literature on the wider social and environmental
determinants of health. Other policy reforms could review the
permanency of some diagnostic labels, address calls for
increased independence in the design and running of scientific
studies,
55
and adjust the structural and legal incentives driving
overdiagnosis.
Concern about overdiagnosis does not preclude awareness that
many people miss out on much needed healthcare. On the
contrary, resources wasted on unnecessary care can be much
better spent treating and preventing genuine illness. The
challenge is to work out which is which, and to produce and
disseminate evidence to help us all make more informed
decisions about when a diagnosis might do us more good than
harm.
We thank the participants at the April 2012 Coolangatta planning meeting
on overdiagnosis: Paul Glasziou, Kirsten McCaffery, Melissa Sweet,
Hilda Bastion, Andrew Wilson, Ian Scott, Suzanne Hill, Alexandra Barratt,
Steve Woloshin, Lisa Schwartz, Fiona Godlee, and Rae Thomas. We
also thank Julia Lowe.
Competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf (available on
request from the corresponding author) and declare: JD is supported
by NHMRC project grant 511217; they have no financial relationships
with any organisations that might have an interest in the submitted work
in the previous three years; all authors were at the April 2012 planning
meeting for the 2013 conference and RM is undertaking a PhD on
overdiagnosis.
Provenance and peer review: Commissioned; externally peer reviewed.
1 Abramson J. Overdosed America: the broken promise of American medicine. Harper,
2004.
2 Brownlee S. Overtreated: why too much medicine is making us sicker and poorer
Bloomsbury, 2007.
3 Welch G, Schwartz L, Woloshin S. Overdiagnosed: making people sick in pursuit of health.
Beacon Press, 2011.
4 Jørgensen K, Gøtzsche P. Overdiagnosis in publicly organised mammography screening
programmes: systematic review of incidence trends. BMJ 2009;339:b2587.
5 Black W. Advances in radiology and the real versus apparent effects of early diagnosis.
Eur J Radiol 1998;27:116–22.
6 Moynihan R, Heath I, Henry D. Selling sickness: the pharmaceutical industry and
disease-mongering. BMJ 2002;324:886-91.
7 Berwick D, Hackbarth, A. Eliminating waste in US health care. JAMA 2012;307:1513-6.
8 Moynihan R, Cassels A. Selling sickness: how the world’s biggest pharmaceutical
companies are turning us all into patients. Nation Books, 2005.
9 Grady D, Redberg R. Less is more: how less health care can result in better health. Arch
Intern Med 2010;170:749-50.
10 European Health Forum Gastein. Innovation and wellbeing: living longer—but are we
living better? Press release, 8 September 2011. www.ehfg.org/826.html#c1950.
11 Choosing Wisely. US physician groups identify commonly used tests or procedures they
say are often not necessary. Press release, 4 April 2012. http://choosingwisely.org/wp-
content/uploads/2012/03/033012_Choosing-Wisely-National-Press-Rls-FINAL.pdf .
12 Welch G, Black W. Overdiagnosis in cancer. JNCI 2010;102:605-13.
13 Lauer M. Pseudodisease, the next great epidemic in coronary atherosclerosis? Arch Intern
Med 2011;171:1268-9.
14 Woolfe S, Harris R. The harms of screening. JAMA 2012;307:565-6.
15 Orme NM, Fletcher JG, Siddiki HA, Harmsen WS, O’Byrne MM, Port JD, et al. Incidental
findings in imaging research: evaluating incidence, benefit, and burden. Arch Intern Med
2010;170:1525-32.
16 Schwartz LM, Woloshin S. Changing disease definitions: implications for disease
prevalence: analysis of the third national health and nutrition examination survey,
1988–1994. Effect Clin Pract 1999;2:76-85.
17 Kaplan R, Ong M. Rationale and public health implications of changing CHD risk factor
definitions. Annu Rev Public Health 2007;28:321-44.
18 Herndon MB, Schwartz LM, Woloshin S, Welch G. Implications of expanding disease
definitions: the case of osteoporosis. Health Aff 2007;26:1702-11.
19 Moynihan R. Merging of marketing and medical science: female sexual dysfunction. BMJ
2010;341:c5050.
20 Moynihan, R. A new deal on disease definition. BMJ 2011;342:d2548.
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2012;344:e3502 doi: 10.1136/bmj.e3502 (Published 29 May 2012) Page 4 of 6
FEATURE

Drivers of overdiagnosis
• Technological changes detecting ever smaller “abnormalities”
• Commercial and professional vested interests
• Conflicted panels producing expanded disease definitions and writing guidelines
• Legal incentives that punish underdiagnosis but not overdiagnosis
• Health system incentives favouring more tests and treatments
• Cultural beliefs that more is better; faith in early detection unmodified by its risks
21 Ahmed A, Blake G, Rymer J, Fogelman I. Screening for osteopenia and osteoporosis:
do the accepted normal ranges lead to overdiagnosis? Osteoporos Int 1997;7:432-8.
22 Hodgkinson J, Mant J, Martin U, Guo B, Hobbs F, Deeks J, et al. Relative effectiveness
of clinic and home blood pressure monitoring compared with ambulatory blood pressure
monitoring in diagnosis of hypertension: systematic review. BMJ 2011;342:d3621.
23 Winearls C, Glassock R. Classification of chronic kidney disease in the elderly: pitfalls
and errors. Nephron Clin Pract 2011;119(suppl 1):c2-4.
24 Biesheuvel C, Barratt A, Howard K, Houssami N, Irwig L. Effects of study methods and
biases on estimates of invasive breast cancer overdetection with mammography screening:
a systematic review. Lancet Oncol 2007;8:1129-38.
25 Morrell S, Barratt,A, Irwig L, Howard K, Biesheuvel C, Armstrong B. Estimates of
overdiagnosis of invasive breast cancer associated with screening mammography Cancer
Causes Control 2010;21:275-82.
26 Kalager M, Adami H, Bretthauer M, Tamimi R. Overdiagnosis of invasive breast cancer
due to mammography screening: results from the Norwegian screening program. Ann
Intern Med 2012;156:491-9.
27 Tan G, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable
nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226-31.
28 Davies L, Welch G. Increasing incidence of thyroid cancer in the United States, 1973-2002.
JAMA 2006;295:2164-7.
29 International Association of Diabetes and Pregnancy Study Groups. Recommendations
on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care
2010;33:676-82.
30 Ryan E. Diagnosing gestational diabetes. Diabetologia 2011;54:480-6.
31 Cundy T. Proposed new diagnostic criteria for gestational diabetes—a pause for thought?
Diabet Med 2012;29:176-80.
32 Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new
equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12.
33 National Kidney Foundation. Clinical practice guidelines for chronic kidney disease:
evaluation, classification and stratification. Am J Kidney Dis 2002;39(suppl 1):s17-31.
34 Glassock R. Estimated glomerular filtration rate: time for a performance review? Kidney
Int 2009;75:1001-3.
35 Winearls C, Haynes, R, Glassock R. CKD staging—evolution not revolution. Nefrologia
2010;30:493-500.
36 Eknoyan G. Chronic kidney disease definition and classification: the quest for refinements.
Kidney Int 2007;72:1183-5.
37 Aaron S, Vandemheen K, Boulet L, McIvor R, FitzGerald J, Hernandez P, et al.
Overdiagnosis of asthma in obese and nonobese adults. CMAJ 2008;179:1121-31.
38 Lucas A, Smeenk F, Smeele I, van Schayck C. Overtreatment with inhaled corticosteroids
and diagnostic problems in primary care patients, an exploratory study. Fam Pract
2008;25:86-91.
39 Prasad V, Rho J, Cifu A. The diagnosis and treatment of pulmonary embolism. Arch Intern
Med 2012 Apr [Epub ahead of print].
40 Weiner R, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United
States. Arch Intern Med 2011;171:831-7.
41 Carrier M. A study to evaluate the safety of withholding anticoagulation in patients with
subsegmental PE who have a negative serial bilateral lower extremity ultrasound (SSPE).
2011. http://clinicaltrials.gov/ct2/show/NCT01455818.
42 Angell M. The epidemic of mental illness: why? New York Review Books 2011 Jun 23.
43 Frances A. The first draft of DSM-V. BMJ 2010;340:c1168.
44 Healy D. The latest mania: selling bipolar disorder. PLoS Med 2006;3:e185.
45 Thomas R. The diagnostic variability in attention deficit hyperactivity disorder. Presentation
to Overdiagnosis Meeting, Coolangatta, 29-30 April 2012.
46 Morrow R, Garland E, Wright J, Maclure M, Taylor S, Dormuth C. Influence of relative
age on diagnosis and treatment of attention-deficit/hyperactivity disorder in children. CMAJ
2012;184:755-62.
47 Heath I, Hippisley-Cox J, Smeeth L. Measuring performance and missing the point. BMJ
2007;335;1075-6.
48 Greene J. Prescribing by numbers; drugs and the definition of disease. Johns Hopkins
University Press, 2007.
49 Fenton J, Jerant A, Bertakis K, Franks P. The cost of satisfaction. Arch Intern Med
2012;172:405-11.
50 Fisher ES, Wennberg DE, Stukel TA, Gottlieb DJ, Lucas FL, Pinder EL. The implications
of regional variations in Medicare spending, part 2: health outcomes and satisfaction with
care. Ann Intern Med 2003;138:288-98.
51 Kramer B. Current and future perspectives on cancer prevention research. National Cancer
Advisory Board, 2012. http://deainfo.nci.nih.gov/advisory/ncab/161_0212/Kramer.pdf.
52 Schwartz L, Woloshin S, Fowler F, Welch G. Enthusiasm for cancer screening in the
United States. JAMA 2004;291:71-8.
53 Elmore J, Fletcher S. Overdiagnosis in breast cancer screening: time to tackle an
underappreciated harm. Ann Intern Med 2012;156:536-7.
54 Taylor B, Wilt T, Welch G. Impact of diastolic and systolic blood pressure on mortality:
implications for the definition of “normal”. J Gen Intern Med 2011;26:685-90.
55 Prasad V, Cifu A, Ioannidis J. Reversals of established medical practices. JAMA
2012;307:37-8.
56 Reich J. A critical appraisal of overdiagnosis: estimates of its magnitude and implications
for lung cancer screening. Thorax 2008;63:377-83.
Cite this as: BMJ 2012;344:e3502
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BMJ 2012;344:e3502 doi: 10.1136/bmj.e3502 (Published 29 May 2012) Page 5 of 6
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Figure
Rates of new diagnosis and death for five types of cancer in the US, 1975-2005. Adapted from Welch and Black
12
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