Overdiagnosis: How Our Compulsion for Diagnosis May Be Harming Children

SPECIAL ARTICLE

AUTHORS: Eric R. Coon, MD,a Ricardo A. Quinonez, MD,b Virginia A. Moyer, MD, MPH,c and Alan R. Schroeder, MDd abstract aDivision of Inpatient Medicine, University of Utah School of Overdiagnosis occurs when a true abnormality is discovered, but de- ’ Medicine, Primary Childrens Hospital, Salt Lake City, Utah; tection of that abnormality does not benefit the patient. It should be bBaylor College of Medicine, San Antonio Children’s Hospital, San Antonio, Texas; cAmerican Board of Pediatrics, Maintenance of distinguished from misdiagnosis, in which the diagnosis is inaccurate, Certification and Quality, Chapel Hill, North Carolina; and and it is not synonymous with overtreatment or overuse, in which ex- dDepartment of Pediatrics, Santa Clara Valley Medical Center, cess medication or procedures are provided to patients for both cor- San Jose, California rect and incorrect diagnoses. Overdiagnosis for adult conditions has KEY WORDS medical education, public health gained a great deal of recognition over the last few years, led by real- izations that certain screening initiatives, such as those for breast and ABBREVIATION ADHD—attention-deficit/hyperactivity disorder prostate cancer, may be harming the very people they were designed to Dr Coon participated in conception and design, drafted the protect. In the fall of 2014, the second international Preventing Over- initial manuscript, and critically reviewed and revised the diagnosis Conference will be held, and the British Medical Journal will manuscript; Drs Quinonez, Moyer, and Schroeder participated in produce an overdiagnosis-themed journal issue. However, overdiagno- conception and design and critically reviewed and revised the manuscript; and all authors approved the final manuscript as sis in children has been less well described. This special article seeks submitted. to raise awareness of the possibility of overdiagnosis in pediatrics, www.pediatrics.org/cgi/doi/10.1542/peds.2014-1778 suggesting that overdiagnosis may affect commonly diagnosed condi- doi:10.1542/peds.2014-1778 tions such as attention-deficit/hyperactivity disorder, bacteremia, food Accepted for publication Aug 20, 2014 allergy, hyperbilirubinemia, obstructive sleep apnea, and urinary tract infection. Through these and other examples, we discuss why over- Address correspondence to Eric R. Coon, MD, Department of Pediatrics, Division of Inpatient Medicine, University of Utah diagnosis occurs and how it may be harming children. Additionally, School of Medicine, Primary Children’s Hospital, 100 North Mario we consider research and education strategies, with the goal to better Capecchi Dr, Salt Lake City, UT 84113. E-mail: [email protected]. elucidate pediatric overdiagnosis and mitigate its influence. Pediatrics edu 2014;134:1–11 PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2014 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

PEDIATRICS Volume 134, Number 5, November 2014 1 Downloaded from www.aappublications.org/news by guest on September 27, 2021 Overdiagnosis is defined as the identi- evaluate the likelihood of benefit from should be noted that randomized trial fication of an abnormality where detec- treatments across populations, it is pos- designs are often limited by a commit- tion will not benefitthepatient.Unlike sible to know the likelihood of benefit ment to internal validity and efficacy, misdiagnosis,thefindingisaccurate;the from diagnostic testing. which limits generalizability. Testing or condition detected may be precisely the screening interventions may show an condition that was meant to be detected RESEARCH METHODS TO effect under idealized trial conditions, (a true-positive). The notion that an ac- INVESTIGATE OVERDIAGNOSIS but post hoc naturalistic studies may be curate diagnosis could be anything but better equipped to evaluate their effec- beneficial runs counter to the conven- Thefollowingexperimentaldesignshave tiveness in real-world conditions. been used to detect overdiagnosis. tional wisdom that the more that is known about a patient, the better. Un- The Natural Experiment: Delayed or Missed Diagnoses Without Patient fortunately, not only do overdiagnosed Randomized Trials of Screening Tests Harm patients fail to benefit from their diagnosis, they may also be harmed. The most convincing examples of over- Diagnoses made after a patient has overcome the abnormality or remained Consider the following common clinical diagnosis come from randomized trials asymptomatic over a lifetime, despite scenarios. An 8-year-old boy with ton- of cancer screening tests. If patients the absence of detection and medical sillar hypertrophy on examination and randomly assigned to screening expe- intervention, suggest overdiagnosis. polysomnography consistent with ob- rience more diagnosis of disease but do not experience net benefit (generally For example, nearly 10% of men in their structive sleep apnea undergoes an measured in terms of overall mortality) 20s and .80% of men in their 70s adenotonsillectomy. A 4 year-old girl compared with those randomly as- have prostate cancer discovered in- with a head injury, 2 episodes of vom- signed to no screening or less screen- cidentally on autopsy after they die iting, and a normal physical examina- ing, overdiagnosis exists. For example, from an accident, yet only 3% of men tion undergoes a head CT scan, which in the recent Canadian trial of screen- dieofprostatecancer.5,6 In other shows a small subdural hematoma, for ing mammography involving almost words, although many men have or which she is admitted to the PICU. A 3- 90 000 women, breast cancer diagno- will have prostate cancer, most are month-oldgirlwithbronchiolitisseenin sis was unsurprisingly more common in not overtly harmed by this condition. an emergency department has an ox- women randomly assigned to receive Indeed, randomized trials of prostate ygen saturation of 94% at triage but annual mammography than in women cancer screening have demonstrated desaturates to 88% while asleep on assigned to no mammography.1 How- increased detection with screening continuous pulse oximetry, prompting ever, over the next 25 years all-cause and without an improvement in mortality.7,8 hospital admission. In each case, the breast cancer–specific mortality were In children, studies have identified pro- diagnoses were accurate; the diag- equivalent in both groups. The authors portions of missed and untreated di- nostic tests detected precisely what estimated that 1 overdiagnosed breast agnoses of bacteremia,9 urinary tract theywereintendedtodetect.Providers cancer occurs for every 424 women who infection (UTI),10 and medium-chain may disagree on the optimal treatment undergo screening mammography. Mam- acyl-coenzyme A dehydrogenase de- approaches for these diagnosed chil- mography was successful in detecting ficiency,11 without any harm to the dren, but the focus of this article is not breast cancer but did not save lives. child (Table 1). This study design can mistreatment or overtreatment but Randomized trials were similarly used be confounded by prognostic factors, rather the incipient event of diagnosis. to demonstrate overdiagnosis of neu- in that missed diagnoses may be sys- fi Did these 3 children bene t from their roblastoma in young children with tematically different (ie, milder or more accurate diagnoses? implementation of universal urine indolent) compared with conditions that For an individual patient, determining screening (Table 1). A German trial found reached detection. whethera diagnosis is beneficial can be unchanged mortality rates from neuro- a nearly impossible task, just as it is blastoma after widespread screening Increasing Disease Incidence but often difficult to tell how much benefit with urinary catecholamines at 1 year of Unchanging Morbidity or Mortality an individual derives from treatment; age and estimated that 62% of neu- An increasing incidence of diagnosis of one can never know with certainty what roblastoma cases identified were aspecific disease should always trigger would have happened if the diagnosis overdiagnosed.2,3 A Canadian trial of suspicion of overdiagnosis. When the had not been made or the treatment not universal screening for neuroblastoma increase in incidence is accompanied given. However, just as it is possible to yielded similar results.4 However, it by an unchanging rate of the outcome

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important to patients (usually mortal- TABLE 1 Examples of Possible Overdiagnosis in Pediatrics ity), overdiagnosis is a likely explanation. Diagnosis Evidence of Overdiagnosis For example, thyroid cancer incidence ADHD The youngest children for a given grade level are significantly increasedalmost two anda half foldfrom morelikelythantheirolderclassmatestoreceiveadiagnosisof 83–85 1973 to 2002, but mortality due to thyroid ADHD. Although this phenomenon has been labeled overdiagnosis, one could argue that misdiagnosis is more 12 cancer did not change. Analogous appropriate (ie, immaturity is pediatric examples include hypoxemia misdiagnosed as ADHD). in bronchiolitis and hyperbilirubinemia Aspiration The natural course of aspiration detected by swallow study in anatomically and neurologically normal infants is complete (Table 1), where increased detection resolution.80,81 It is unknown whether making this diagnosis and treatment of both conditions has benefits infants. The largest assessment of outcomes for not decreased mortality.13,14 An alter- neurologically impaired infants found that fundoplication did 82 native explanation could be that a clini- not reduce their risk of hospitalization for respiratory illness. Bacteremia A trial of children age 3–36 mo presenting to an emergency cally important increase in incidence department with fever .39°C treated 19 children with occurred, but an otherwise higher rate bacteremia with placebo (no antibiotic).9 Eighteen children of outcomes important to patients was had spontaneous resolution of bacteremia at 48 h. None developed serious morbidity (meningitis, pneumonia, bone or exactly matched by effective treatment joint infection, cellulitis). modalities, keeping outcomes constant. Cholelithiasis 50% of children diagnosed with cholelithiasis in 1 study were This explanation requires both a biologic completely asymptomaticat diagnosis, of whom 95% were free of complications on long-term follow-up.86 mechanism to explain a truly increased Food allergy Children can have positive immunoglobulin E test results incidence and evidence of improved treat- indicating sensitization but not necessarily suffer from a ment outcomes. clinical allergy.87 For example, 17% of people are sensitized to a major food allergen, but only 2.5% have a clinical food allergy.88 Although it is clear that the most con- Gastroesophageal reflux Reflux is common in the first 6 mo of age and nearly completely clusiveevidence of overdiagnosis comes resolves by 12 mo of age, independent of any medical 89,90 from adult trials of cancer screening, it interventions. A randomized trial found no benefitto treatment of symptoms attributed to gastroesophageal reflux has been suggested that overdiagnosis disease in infants but did find that medication increased the also affects nonneoplastic, common risk of lower respiratory tract infections.91 Yet adult conditions such as hypertension, gastroesophageal reflux disease diagnoses and treatments with medication for infants are common and increasing.92,93 15 diabetes, and osteoporosis. In these Hyperbilirubinemia Therewasnochangeinmortalityduetokernicterusbetween1979 chronic diseases, lowering the thresh- and 2006,14 despite increased vigilance for old values for disease has further in- hyperbilirubinemia, including bilirubin testing and phototherapy.94,95 creased the risk of overdiagnosis.15 Hypercholesterolemia The 2011 National Heart, Lung, and Blood Institute guidelines Similarly, overdiagnosis is probably af- recommend universal screening for children age 9–11 and fecting routine conditions in pediatrics. potentially qualify 200 000 children for treatment,96 with However, although the importance of unclear evidence for long-term harms and benefits of diagnosis and treatment.97–99 overdiagnosis as a driver of avoidable Hypoxemia in bronchiolitis Hospital admissions for children with bronchiolitis have and potentially harmful medical care in significantly increased since 1980, a period coinciding with adult populations has gained promi- increased use of pulse oximetry, yet mortality from bronchiolitis during the same time period has been 16 nence recently, through conferences, unchanged.13,100 Oxygen saturation changes as small as 2% books,15 and dedicated themed journal significantly increase a physician’s decision for admission, issues,17 the phenomenon is rarely de- and the diagnosis of hypoxemia by continuous pulse oximetry scribed in pediatrics. prolongs hospitalization, but there is no evidence that supplemental oxygen for transient desaturations benefits children.101–103 Medium-chain acyl-coenzyme Aportionofnewbornsidentifiedbynewbornscreeningmaynever OVERDIAGNOSIS IN CHILDREN A dehydrogenase deficiency experience symptoms of their enzymatic defect. Studies have There will almost always be a proportion identified affected but completely asymptomatic older siblings of screening-identified newborns,11 and some mutations of patients who benefit from any di- identified by newborn screening have acylcarnitine profiles agnosis,including the exampleswe have that normalize over time.104 chosen. In evaluating the importance Neuroblastoma A portion of neuroblastoma diagnoses will regress without treatment.105 Screening children for neuroblastoma identifies of overdiagnosis in a condition at the more lower-stage cancers but does not reduce end-stage populationlevel,weproposefocusingon neuroblastoma or mortality.2,4 the frequency of overdiagnoses relative

PEDIATRICS Volume 134, Number 5, November 2014 3 Downloaded from www.aappublications.org/news by guest on September 27, 2021 TABLE 1 Continued pediatrics: physical effects, psycholog- Diagnosis Evidence of Overdiagnosis ical effects, financial strain, and op- 25 OSA In 1 trial, almost half of children with OSA randomized to watchful portunity cost. waitinghadcompletenormalizationoftheirpolysomnographic 106 findings 7 mo after enrollment. The same trial failed to show Physical Effects a benefit for the primary outcome (attention and executive function) after surgical intervention for OSA. Tonsillectomy The physical effects of testing and in- 107 rates nearly doubled between 1996 and 2006, a proportion terventions motivated by overdiagnoses of which probably are attributable to the surgical indication of OSA, which increased from 12% of patients in 1970 to 77% in are the most visible harms of unnec- 2005.108 essary detection of an abnormality. Un- Skull fracture Children with isolated skull fractures have excellent outcomes til recently, the standard of care for without neurosurgical intervention, yet they are subjected to repeat CT scanning and often hospitalized.109–111 small, localized adrenal tumors in in- UTI AccordingtoaPediatricResearchinOfficeSettingsstudyofyoung, fants, including those overdiagnosed by febrile infants, of 807 febrile infants never tested or treated for neuroblastoma screening, was surgical UTI, 61 were predicted to have a UTI based on the application of predictors of UTI in infants who did undergo urine testing.10 resection, the mortality of which is 2% Only 2 of the 807 infants not initially tested or treated were or higher.26 For young infants with fe- later diagnosed with a UTI, and none suffered immediate ver, the detection of bacteremia leads morbidity or mortality. to prolongation of antibiotic therapy,27 VUR Most VUR, includinghigh-grade VUR, resolves over time, and few if any interventions for VUR decrease rates of renal scarring or often via a peripherally inserted cen- insufficiency.112,113 tral catheter, for which the complica- OSA, obstructive sleep apnea; UTI, urinary tract infection; VUR, vesicoureteral reflux. tion rate necessitating line removal in children ,1yearofageis48%.28 The gold standard diagnostic test for aspiration, to needed diagnoses, the ratio of po- fants are treated for hyperbilirubinemia avideofluoroscopic swallow study, expo- tential benefits from needed diagnoses in the United States, at a cost of $150 ses subjects to radiation, and an as- to potential harms from overdiagnoses, million per year for the healthy term piration diagnosis often results in an and the amount of resource utilization cohort.20 Because kernicterus is a dev- intervention, ranging from thickening resulting from overdiagnosis. Thus, the astating and potentially lethal condi- feeds to surgery for gastric tubes and examples in Table 1 feature diagnoses tion, overdiagnosis and overtreatment of Nissen fundoplications. with unclear or infrequent opportunity hyperbilirubinemia have been accepted for benefit, the possibility for harm, or as a reasonable tradeoff. However, the high resource utilization. potential for harm from hospitalization Psychological Effects For example, universal or nearly uni- and treatment of hyperbilirubinemia Subtle but potentially common byproducts versal bilirubin screening is common in has not been adequately researched, of overdiagnosis are psychological ef- the United States, intended to decrease and recent findings of a possible asso- fects, because all diagnoses, whether infants’ risk of kernicterus, a rare but ciation between phototherapy and child- beneficial to the patient or not, change devastating neurologic condition. How- hood leukemia may affect the risk/benefit the perception of the child for the child, ever, the number of infants who must be analysis.21,22 his or her caregivers, and society. Fun- treated with phototherapy to prevent damentally, diagnoses connote abnor- 1 infant from needing exchange trans- HOW IS OVERDIAGNOSIS mality, something to be remedied. One HARMFUL? fusion is high,18 meaning that most in- recent study found that parents given fants with hyperbilirubinemia do not Medical tests are more accessible, a hypothetical clinical scenario of a child benefit from diagnosis and treatment. rapid, and frequently consumed than with a gastroesophageal reflux disease The number needed to treat for the ever before. Discussions between pa- label were more likely to believe the more important outcome, kernicterus, tientsandproviderstendtofocusonthe child would benefit from medication is probably much larger. Unfortunately, potential benefits of testing, with less than parents given the same scenario as concluded by the US Preventive regard for potential harms.23 Yet a sin- without a gastroesophageal reflux dis- Services Task Force19 in 2009, evidence gle test can give rise to a cascade of ease label, a belief that persisted even to support the efficacy of screening events, many of which have the poten- when parents were told that the medi- and treatment to reduce the risk of tial to harm.24 We use a recently pub- cations were probably ineffective.29 kernicterus is inadequate. Nevertheless, lished taxonomy of 4 harm domains to Parental belief in their child’s vulnera- 10 to 80 in 1000 term and preterm in- frame the harms of overdiagnosis in bility after illness, despite full recovery,

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was first described in 1964.30 Unfor- infants with elevated bilirubin values leave a practitioner feeling validated by tunately, the debilitating effects of the are unlikely to be included in waste hisorherdecisiontoobtainthe CT scan, “vulnerable child syndrome” require estimates, despite the fact that in some even though detection of these abnor- only that a diagnosis is made, regard- cases these interventions are not ben- malities is unlikely to change manage- less of a child’s ability to benefitfrom eficial. The annual US health care costs mentinawaythatbenefitsthe patient.If the diagnosis. Forty percent of junior for each of these conditions are $543 physicians are not aware of the po- high school children with a history of million,39 $1.6 billion,40 and $150 million,20 tentialharmsofoverdiagnosis,patients an innocent heart murmur or other respectively. and families cannot be expected to ap- cardiac nondisease in 1 study suffered preciate them either. A survey of adult physical and psychological restriction Opportunity Cost medicine providers found that their after their diagnosis.31 In another Finally, consideration must be given to understanding of cancer screening sta- study, parents of children with feeding the opportunity cost of overdiagnosis, tistics, including overdiagnosis, was and crying problems in infancy necessi- thepossibilitythatneededmedicalcare poor. Almost half of those surveyed tating a change in formula were more is not provided because of unnecessary believedthatfindingmorecancercases likely to perceive their child as vulnera- diagnoses, their subsequent interven- in screened as opposed to unscreened ble .3 years later, despite being no tions, and the psychological and finan- populations proved that screening saved more likely to report allergies, asthma, cial burdens they impose. Unfortunately, lives.41 Unfortunately, similar knowledge or eczema for their child.32 Finally, par- this is an almost completely unstudied assessments have not been performed ents of infants with jaundice or photo- harm of overdiagnosis. The value of in pediatrics. therapy exposure are more likely to patient and family time and the quantity Intolerance of uncertainty can be a seek medical attention for their child of their financial resources consumed powerful motivator for diagnostic test- well after jaundice resolution,33 per- by care related to overdiagnosis are ing.42–44 Providers may be troubled by ceive subsequent illnesses as moderate unquantified. The attention and re- not having an answer to explain a or severe, and fear leaving their baby sources that providers could divert to patient’s complaint and respond to this with any other caregiver.34 fi patients who stand to bene tfromdi- uncertainty by relying on diagnostic Diagnoses also affect how children are agnoses and treatments, were they not tests or expert consultation. Provider treated by society. Approximately one- consumed by the overdiagnosed, are perceptions that families want an an- fi third of children with food allergy also unquanti ed. swer, that testing expresses caring, ∼ (a diagnosis now given to 8% of and that watchful waiting ignores pa- children) suffer from allergy-related WHAT IS DRIVING tient needs may propagate this behav- bullying and an associated lower qual- OVERDIAGNOSIS? ior. For example, in a study investigating ity of life.35,36 The widespread bullying of Drivers of excessive care are poorly decisions to obtain head CT scans in children with this diagnosis has pro- quantified in health care in general, and children with minor blunt head trauma, mpted the “It’sNotaJoke” campaign, we are aware of no research quantifying providers acknowledged the influence highlighting the emotional toll of food the factors that motivate pediatricians of parental anxiety or request on their allergy bullying.37 to test or treat. Drawing on the limited decision to order more CT scans. In- available literature from adult medicine, terestingly, white non-Hispanic children Financial Strain we propose several candidate drivers of were more likely to undergo unnec- Overdiagnosis is also harmful because overdiagnosis in pediatrics. essary cranial CT scanning than their 45 of the resultant financial costs. Un- minority counterparts. necessary and wasteful care are esti- Physician Factors The culture of medical education is an mated to constitute 21% to 47% of all Overdiagnosis is rarely addressed in early impetus for training providers to expenditures, which probably ignores the pediatric literature, and some pe- find comfort in commission and fear in the contribution of overdiagnosis given diatric providers may not be aware that uncertainty.46 Problem-based learning that accurate diagnoses, regardless of the detection of abnormalities could be strategies in medical school encour- their benefit to the patient, are assumed harmful. If a diagnostic test discovers age a shotgun approach, which tends to be necessary.38 Providing oxygen to the condition it was meant to discover, to reward unusual diagnoses and children with bronchiolitis, stimulants how could it have been unnecessary or contributes to overtesting and over- to students with attention or hyperac- even harmful? A head CT scan revealing diagnosis.47–49 An emphasis on avoid- tivity problems, and phototherapy to a small bleed or a skull fracture might ing omission errors in case report

PEDIATRICS Volume 134, Number 5, November 2014 5 Downloaded from www.aappublications.org/news by guest on September 27, 2021 conferences and morbidity and mortal- Industry Influence US patient groups found that 80% re- 68 ity conferences may strengthen these Industry interests contribute to over- ceived industry funding. The National tendencies. Given this milieu, the pro- diagnosis by lobbying for widened di- Alliance on Mental Illness, a mental duction of providers eager for diagnosis, agnostic boundaries and using the health advocacy organization, received but unsighted of its possibility to harm, media to generate demand for diag- $23 million, or approximately three- is only natural. nosis, both of which create more pa- quarters of its donations, from drug 69 Finally, fear of litigation may motivate tients and more profit.60 For example, makers between 2006 and 2008. unnecessary testing, exposing patients lowering the definition of hypercho- to unnecessary diagnoses. Indeed, er- lesterolemia in adults from 240 to 200 Public Psyche rors of omission (a patient is harmed mg/dL, a 2002 recommendation made Belief in scientific advance and a tech- because a necessary test or treatment by an expert panel where 8 of 9 pan- nological imperative, a confidence that was not provided) are more frequently elists had financial conflicts of interest, the use of technology to detect disease punished by litigation than errors of created .42 million new diagnoses.61,62 is always beneficial, also drive over- commission (a patient is harmed be- Such conflicts of interest in defining diagnosis. A positive feedback loop of cause an unnecessary test or treatment disease are not unusual. In one study, testingensues,inwhichthe testresults, was provided).50 However, although 75% of members of panels responsible independent of the actual value (posi- providers often cite defensive medicine for defining the most common diseases tive, negative, false-positive, or false- as a stimulus for unnecessary testing in the United States had ties to industry negative), confirm for patients that and care,51,52 reforms to lessen provider that stood to benefit from expanded they should have been tested and make liability do not necessarily change their definitions.63 The 2012 attention-deficit/ them more likely to seek additional behavior.53 hyperactivity disorder (ADHD) guide- testing.15 In a survey of adults, 98% of line panel included 9 members, 5 of those who had experienced a false- System Incentives whom had industry ties to manu- positive test were glad they had the facturers of widely used medications initial screening test, and 73% of all External systemic forces may incen- for ADHD.63 Based on this committee’s respondents would forgo $1000 in cash tivize testing and diagnosis. Fee-for- recommendations, the definition of for a total body CT scan.70 Two but- service reimbursement, a target for ADHD was broadened to include chil- tresses of public enthusiasm for reform, financially rewards providers dren 4 to 18 years old (previously 6–12 screening are lead time and length for providing more, and potentially ex- years old).64 Although it is unclear how bias, which mistakenly bolster the cessive, care. Supply-sensitive care, many new diagnoses of ADHD this ex- argument for testing by erroneously where higher capacity in the form of pansion created, diagnostic creep has overestimating prevalence and improved hospital beds and imaging modalities outcomes. Lead time bias occurs when drives medical utilization, inevitably un- resulted in the prescription of stimulants to .10 000 toddlers aged 2 and diagnoses are identified earlier than covers patient abnormalities.54 Pro- 3yearsold.65 Similar to concerns they would be discovered clinically, posed pediatric quality indicators tend falsely appearing to prolong survival, to encourage greater testing and treat- generated by the extension of the diagnosis of depressive disorder to in- and length bias occurs when screening ment. In one evaluation, only 5 in 242 identifies disproportionately milder proposed pediatric ambulatory indica- clude bereavement, the ADHD expansion diagnoses.71 tors focused on problems of overuse risks medicalizing variations of normal 66 (compared with 225 in 242 for un- human behavior. THE WAY FORWARD deruse),55 whereas none of the 62 Patientsarealsoinfluencedby industry. pediatric emergency department indi- Pharmaceutical companies spent $4.5 A research agenda aimed at evaluating cators in a separate assessment eval- billion on direct-to-consumer market- the harms and benefits of individual uated unnecessary tests.56 In addition, ing in 2009.67 Advertisements capitalize pediatric diagnoses and the frequency physicians more readily improve on on our fear of undiagnosed disease of overdiagnosis is needed. Of the ex- quality indicators aimed at underuse and urge us to see our doctor for amples presented here, the only conclu- as opposed to overuse.57 Finally, time testing. Industry also reaches patients sive evidence of pediatric overdiagnosis constraints and loss of continuity of through patient advocacy groups. Once is for neuroblastoma screening.2–4 Cur- care lead to a substitution of testing for considered unbiased, third-party advo- rently, most studies of diagnostic tests thorough review of records and patient cacy groups are often used to deliver report on test accuracy rather than assessment.58,59 the same message. A random sample of evaluating whether the test results led

6 COON et al Downloaded from www.aappublications.org/news by guest on September 27, 2021 SPECIAL ARTICLE to important outcomes that benefited exposure to cancer screening pro- overdiagnosis. Although it is unclear how patients. The 3 research methods pre- grams reported being advised by their this type of shared decision-making viously outlined (randomized trials, nat- physician about the risk of overdiagno- would affect diagnostic testing in chil- ural experiments, and comparison of sis or overtreatment from screening.75 dren, examples from adult medicine incidence versus outcomes) provide rea- Future pediatric research can evaluate reveal that many patients opt out of sonable starting points for studying the impact on patient decision-making testswhenprovidedcomprehensive the possibility of overdiagnosis for a when patients are exposed to farther- evidence on risks and benefits.76 particular abnormality. Additionally, reaching impacts of a diagnosis. In Ta- Finally, the incorporation of over- practice variation may be an impor- ble 3, we list several common clinical diagnosis into medical education cur- tant beacon for overdiagnosis. Condi- scenarios where diagnostic tests are riculaiscritical. Studentsmay be guided tions for which testing and diagnostic performed and provide examples of both to produce carefully crafted differ- variation exist, but important patient proximate and long-term perspectives entials and workups that are proba- outcomes do not differ, would suggest on why the test might be indicated. The bilistic rather than “possibilistic.”77 overdiagnosis. proximate perspective addresses the Differential-generating teaching ses- Because providers may be reluctant to immediate rationale for a diagnostic test, sions can acknowledge the risk of over- accept evidence that is counter to their whereas the long-term perspective as- diagnosis, and morbidity and mortality customary practice or experience, in- sesses possible diagnostic results and conferences can expand to include cases vestigations delineating pediatric over- subsequent interventions. Both per- of harms caused by overdiagnosis. The diagnosisultimatelymustbeaugmented spectives are important, but discussions Do No Harm Project, vignettes produced by advocacy and awareness efforts. about less immediate diagnostic corol- by University of Colorado internal medi- The campaigns in Table 2 have each laries, in particular, will help patients cine residents illustrating harms from made strong contributions to this ob- and providers frame testing deci- medical overuse, can serve as a model jective. Choosing Wisely is an example sions within the context of potential in the development of pediatric-specific of dissemination and implementation of measures that aid providers in de- creasing practice variation and un- TABLE 2 Overdiagnosis Awareness and Mitigation Resources necessary diagnostic testing, which Resource Description Website may reduce the risk of overdiagnosis. Overdiagnosis Annual international conference http://www.preventingoverdiagnosis.net/ Specifically, the majority of the pediatric Conference British Medical “Aim is to highlight threat to human health http://www.bmj.com/too-much-medicine Choosing Wisely initiatives decrease Journal: posed by overdiagnosis and the waste of opportunities for overdiagnosis, with Too Much resources on unnecessary care.” recommendations that limit the use of Medicine Overdiagnosed: Nonfiction book by Gilbert Welch that CT scans, MRI, chest radiographs, apnea Making explores overdiagnosis in adults. monitors, food allergy screening, and People Sick in the continuous pulse oximetry.72,73 In gen- Pursuit of Health Lown Institute Advocacy group promoting delivery of the http://lowninstitute.org/ eral, guidelines that endorse testing can right care to patients. address the harms of overdiagnosis Choosing Wisely Campaign to promote care that is http://www.choosingwisely.org/ and support strong recommendations “supported by evidence, not duplicative, free from harm, and for testing with evidence that impor- truly necessary.” tant outcomes for children are improved Journal of the Initiative to highlight the risks and http://jamanetwork.com/collection. by diagnosis. Use of the US Preventive American harms of unnecessary care, including aspx?categoryid=6017 Services Task Force analytic framework, Medical overdiagnosis. Association which considers both harms and bene- Internal fits and clearly delineates pertinent out- Medicine “ ” comes, would help guideline panels in Less Is More and this endeavor.74 “Teachable Despite efforts made by the organi- Moment” sections zations listed in Table 2, there remains Hospital Pediatrics Case reports submitted by trainees http://www.hospitalpediatrics.org/ a large proportion of underinformed “Bending highlighting cases of low-value care patients: Only 9.5% of adults with high the Value Curve” in pediatrics.

PEDIATRICS Volume 134, Number 5, November 2014 7 Downloaded from www.aappublications.org/news by guest on September 27, 2021 TABLE 3 “Why Are We Doing This test?”: Proximate Versus Long-Term Implications for Diagnostic does not occur with watchful waiting, Testing minimal interventions, with the poten- Diagnostic Test Clinical Scenario Proximate Reason to Test Long-Term Implications of tial for diagnosis, are used. Such a Diagnosis patient approach is important, be- fl Voiding Infant with febrile Vesicoureteral re ux is often Possible interventions for cause the risk of overdiagnosis is cystourethrogram urinary tract found in children with vesicoureteral reflux infection urinary tract infection. include long-term greatest for the child with no symp- prophylactic antibiotics, toms or a few nonspecific symptoms; urologic surgery, and the milder an abnormality, the less additional imagingstudies. fi 15 Sleep study Toddler who snores Snoring may reflect If obstructive sleep apnea is potential for bene t. If the magni- loudly at night obstructive sleep apnea. detected, possible tude of hypothetical benefit is small interventions include for pursuing a diagnosis and the pos- medications, continuous or bilevel positive airway sibility of harm exists, perhaps the pressure, and child and family are better off avoiding adenotonsillectomy. diagnostic exposure. Videofluoroscopic Neurologically Aspiration of food or gastric Diagnosis of aspiration often swallow study impaired child contents is common and leads to recommendations with frequent may contribute to frequent for changes in feeding CONCLUSIONS respiratory respiratory illnesses. practices, including infections thickening food, cessation Substantial proportions of children may of oral feeding, placement not benefit from commonly pursued of a feeding tube through pediatric diagnoses. In some cases, the child’s nose, or surgery to decrease reflux of overdiagnosis is necessary to ensure gastric contents. larger gains for the children who do Serum cholesterol 11-y-old child presents Reduction of elevated Detection of abnormal benefit from the diagnosis. However,for for well child cholesterol levels in adults cholesterol may lead to many diagnostic tests, the ratio of ben- examination decreases rates of lifestyle interventions, cardiovascular morbidity medications, and efit to harm resulting from the diagno- and mortality. Pediatric retesting. sis is incompletely understood. Patient, guidelines now suggest physician, investigator, and society-wide screening all children age fi 9–11 y. attention to this complex bene t assessment will help ensure that we, first, do no harm. curricula to directly address over- a stepped approach can be undertaken diagnosis.78 Perhaps most importantly, to reduce the risk of overdiagnosis. This ACKNOWLEDGMENTS medical education can discourage black- method begins with normalizing prob- The authors thank Christopher G. and-white thinking, instead nurturing lems, if appropriate, and pursuing a pe- Maloney, MD, PhD, and Thomas B. critical thinking and comfort with un- riod of watchful waiting.79 If resolution Newman, MD, MPH, for their thoughtful certainty. If symptoms are not severe, or an acceptable level of improvement review of this article.

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