A Cieszanowski

A Mamourian

CA Nelson

CO Schmidt

Eline M. Bunnik

F Bamberg

FG Miller

J Illes

JM Royal

JM Shoemaker

K Hegenscheid

L Reneman

Meike W. Vernooij

MP Kirschen

MW Vernooij

NM Orme

RI Grossman

SE Petersen

SM Wolf

TC Booth

Z Morris

Crossref

COMMENTARYIncidental findings in population imaging revisitedEline M. Bunnik1 • Meike W. Vernooij2Received: 1 December 2015 / Accepted: 28 January 2016 / Published online: 9 February 2016 The Author(s) 2016. This article is published with open access at Springerlink.comImaging techniques are deployed in human subjectsresearch on an increasingly large scale. Worldwide, imagesof the brain, the abdomen or the whole body are acquired inclinical and population-based cohort studies, and in neu-roscience, cognitive science and behavioural sciencestudies. Many of these imaging studies are performed involunteers who are presumed healthy and free of anysymptoms. Yet, even in healthy volunteers, structuralabnormalities are detected quite frequently, in approxi-mately 2–3 % of MRI scans of the brain [1, 2], and pos-sibly in over a third of whole-body MRI scans [3]. So-called incidental findings may be of clinical or reproductivesignificance to research participants. Incidental findingshave commonly been regarded as findings that are unre-lated to the aims of the study and are discovered unex-pectedly in the course of conducting research [4].The word ‘incidental’ literally means ‘‘being likely toensue as a chance or minor consequence’’ or ‘‘occurringmerely by chance or without intention or calculation’’ [5].Incidental findings have historically been understood asobservations ‘stumbled upon’ by researchers or radiolo-gists. This presupposes a passive, unprepared observer,upon whom an abnormality ‘happens’ by chance. Theethics of incidental findings has generally aligned with thisnotion. Ethical guidance on the detection, management andcommunication of incidental findings requires researchersor institutions to have (no more than) a ‘contingency plan’in place: if researchers stumble upon something that maybe relevant to the health of the participant, then they shouldact. Most guidance documents do state that the actions tobe taken (e.g. consultation of an expert radiologist forconfirmation of the finding, communication of the findingto the participant or their physician) should be outlined in apredesigned protocol or pathway to be approved by aninstitutional review board [4, 6, 7], which should be com-municated beforehand with research participants. Thus,current ethical guidance covers mostly what happens afterincidental findings have been detected, but it does notexpressly address whether incidental findings should bedetected or what actions should be taken to avoid or ensurethe detection incidental findings. A prominent topic ofdebate is whether routine review of research scans isrequired. Practices vary considerably across countries andstudies [7, 8]: among the largest population-based studiescurrently being conducted in Europe, approaches for thedetection of incidental findings range from only limitedhandling of those findings that are stumbled upon byradiographers during scan acquisition [9] to having allscans read by dedicated radiologists [10]. In what followswe explain why the research community must take aproactive role and resolve this debate.Incidental findings are no longer unexpectedAs imaging of healthy participants is becoming morewidespread and researchers’ experience with the detection,management and clinical follow-up of incidental findings isconsequently becoming more thorough, incidental findingscan no longer be considered to be unexpected. Theprevalence of clinically significant incidental findings& Eline M. Bunnike.bunnik@erasmusmc.nl1 Department of Medical Ethics and Philosophy of Medicine,Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam,The Netherlands2 Departments of Radiology and Epidemiology, Erasmus MC,Wytemaweg 80, 3015 CN Rotterdam, The Netherlands123Eur J Epidemiol (2016) 31:1–4DOI 10.1007/s10654-016-0123-0among healthy participants is known to be around 2.7 % inMRI of the brain [1], which implies a number needed toscan of around 37 for one significant finding [1, 2]. Theprevalence may be slightly higher in elderly subjects [2],but even in children and adolescents, incidental findingsoccur [11]. Incidental findings may be (much) more fre-quent in other areas of the body, such as the abdomen orchest [3, 12]. Based on this accumulating evidence,researchers can thus anticipate, firstly: that incidental find-ings will occur; and, secondly, for specified study popula-tions (i.e. depending on age range, health status): how manyand what types of incidental findings are likely to occur.Incidental findings are no longer accidentalIncidental findings are the result not of chance, but ofchoices made—intentionally or unintentionally—by theresearcher, research team and/or institution. The technicalparameters of the imaging study, the training and instruc-tion of the research staff, the time and resources spent onthe reviewing of scans, are all factors that will affect thedetection of incidental findings.First, researchers can influence the occurrence of inci-dental findings through the design of the scan protocolitself, through decisions regarding the technical parametersor the sequences to be acquired and the quality thereof: e.g.in brain imaging, T2 weighted and fluid-attenuated inver-sion recovery (FLAIR) images are of greater diagnosticutility than T1 weighted images or functional MRI and willgenerally lead to the detection of more incidental findings[2, 13].Second, whether or not incidental findings are detecteddepends in part on the person who is looking at the scans.As radiographers are trained differently from radiologists,they will perceive different things when looking at thesame scan. Likewise, PhD-researchers in neuroscience orpsychology university departments will perceive differ-ently from hospital-based research staff, and so on. Notonly the researchers’ background and training, but alsotheir personality traits (e.g. conscientiousness) or state ofmind (e.g. how much sleep they have had) may affect whatthey see when looking at MRI scans.Third, whether incidental findings are detected dependson the instructions given to the person who is looking at thescans: are they asked to only check the quality of theimages or also to check for abnormalities? Are they trainedto review scans for abnormalities? And even: how muchimportance is placed on the task of reviewing by supervi-sors? Does the reviewer have access to expert opinionwhen in doubt?Fourth, what the researcher sees on MRI scans dependson the time and the timing allocated for (clinical) review ofscans. Are scans reviewed on the spot or later on? Are theyto be glanced over in a few seconds or scrutinized forminutes? Are those who are asked to review scans allottedsufficient time or are they working under stress?Additional factors that can influence the detection ofincidental findings may include the goals of the research(medical or non-medical), the location of the researchcentre (whether the research setting is hospital-based or, forinstance, a neuroscience lab at a psychology department),and the research population (e.g. healthy student-volun-teers or the elderly). The same researcher may see differ-ently when reviewing scans for a medically oriented studyor a study with a different (e.g. behavioural) orientation, ina hospital-based research setting or in a neuroscience lab.Context often colours perception.These and others factors are likely to influence the wayscans are ‘looked at’. Technical and organizational factorswork together to fashion the salience of abnormalities andtherewith to bring about the detection of incidental find-ings. The occurrence of incidental findings is thus depen-dent not only on the age and health status of researchparticipants, but also—and potentially equally or moreso—on choices made by researchers concerning the scanprotocol, the selection and instruction of scanner operators,and the clinical review (or not) of scans. Incidental findingsare not ‘discovered’ but ‘created’. They are not accidental:knowingly or unknowingly, they are orchestrated.Ethical implicationsAlthough incidental findings do not always lead to healthbenefits [14] and are associated with risks (e.g. medicalcosts, psychological harms and burdens of unnecessaryfollow-up testing and overtreatment) [13, 15], it is widelyendorsed that if a researcher detects a finding of clinicalrelevance, he or she has a ‘duty to disclose’ the finding tothe participant [6, 7, 16]. We have tried to unravel the blackbox of the ‘if’ within that maxim: incidental findings do nothappen accidentally, but are brought about. They are theresult of technical, social and institutional factors that arecontrolled by researchers, research teams, institutionalreview boards and funding organizations. The researchcommunity should take responsibility for the—control-lable—factors within the research setting that will affectthe likelihood of detection of incidental findings.Now what does taking responsibility mean? Whatchoices—regarding the scan protocol, the staff tasked withreviewing scans and their training and instruction—shouldbe made? Are all choices equally justifiable? Given thevariation in research settings, research aims and profes-sionals involved in research imaging, it will hardly bepossible to formulate a one-size-fits-all recommendation2 E. M. Bunnik, M. W. Vernooij123for the management of incidental findings. Rather, ethicalguidance should be differentiated across research settings.We will take routine review of research scans as anexample of how to go about the task of differentiation.The crucial consideration in the ethics of incidentalfindings, we argue, is this: participants’ expectations shouldbe met—to a reasonable extent. Research participants tendto trust that abnormalities—if present—will be detectedand communicated to them [15]. A mismatch betweenpractices of incidental findings and subjects’ expectationsmay undermine informed consent and may lead to harm(e.g. through false reassurance) [17, 18]. Mismatches canbasically be resolved in two ways: first, by ‘lifting up’research practice (e.g. by indeed offering routine review);or second, by bringing down participants’ expectations(e.g. by informing participants about a no-feedback policy).The latter may be morally unacceptable in some—but notall—research settings.Routine clinical review is time-consuming and costly,and may not be feasible for all research groups or institu-tions. Some groups may thus decide to instruct radiogra-phers to review scans on the spot for quality only, and toavoid the detection of abnormalities. This approach is oftenaccompanied by an informed consent process in whichparticipants are told that ‘no one will look at the scans’and/or that ‘no feedback will be given’. This policy may bedefensible in certain research contexts, for instance, inneuroscience, cognitive science or behavioural sciencelaboratories in which studies are conducted, for example,using fMRI of the brain among healthy student–volunteers.It is conceivable that in such research contexts, theinformed consent process can be successfully used todownplay participants’ expectations [19] and to rebut theso-called diagnostic misconception among participants[16]. After all, it can be explained that the images acquiredare of limited diagnostic utility: potentially significantabnormalities can easily be missed (i.e. false negativeerrors), even by trained radiologists, while visible abnor-malities may be artefacts (i.e. false positive errors) [16]. Itwould be a waste of resources to have qualified radiologistsreview fMR images of the brain acquired for non-medicalresearch purposes: fMR images lack informative value.In other research contexts, however, we contend that—some form of—routine review of research scans is morallyrequired. For instance, research teams that are hospital-based, have access to clinical expertise and/or conducthealth-related studies for which sequences of diagnosticutility are acquired, such as T1 and T2 weighted and/orFLAIR images, should perform some sort of structuredreview for clinically relevant abnormalities. For in suchclearly medical research settings, research participantswill—reasonably—expect obvious and important abnor-malities to be detected and fed back [15]. Furthermore, thevast majority of participants of clinical or population-basedcohort studies prefer to know about incidental findings, andindicate an interest in learning relevant health informationto which they might otherwise not have access [18, 20].The principle of reciprocity [21] coupled with the—logis-tically—relative ease with which diagnostic-quality scanscan be checked for apparent abnormalities by trained per-sonnel, requires researchers to arrange routine review.Though routine review by a clinical radiologist need notentail unbearable financial costs [22], less costly pathwaysmay be feasible, too: research personnel can be trained todistinguish normal from abnormal scans and to send thelatter on—in a second step–for expert opinion. An expertradiologist should confirm the clinical significance of anapparent abnormality before it is fed back to the researchparticipant [6, 7]. Therefore, researchers should makearrangements for second-step consultation with expertradiologists prior to the start of any imaging study. A two-step approach may be more feasible in some body partsthan others, e.g. brain imaging versus abdominal imaging.Any selected approach for the handling of incidentalfindings should be implemented in a standardized manner,communicated with research participants as part of theinformed consent process, and monitored through a qualityassurance program.Routine review of research scans is but one controllablefactor in the ‘creation’ of incidental findings. It is beyondthe scope of this article to outline differentiated ethicalrecommendations for all controllable factors in all researchsettings.ConclusionIn the above, we have tried to show that it will no longersuffice to have established a pathway for when incidentalfindings have ‘happened’. Researchers and research insti-tutions must make up their minds: should they facilitate oravoid the detection of incidental findings? We have arguedthat there is indeed an answer to that question, though itdepends on the research setting. Researchers should planahead and assume their decisive roles in the orchestrationof incidental findings. Ethically responsible pathways forthe detection, management and communication of inci-dental findings should accommodate research participants’expectations. In population-based cohort studies of aclearly medical character or studies in which diagnostic-quality images are acquired, all research scans should bereviewed—in one way or another—for relevantabnormalities.Acknowledgements The present article is a result of a qualitativeresearch project, which was funded by the Netherlands OrganisationIncidental findings in population imaging revisited 3123for Health Research and Development (ZonMw, No. 731010004), andconducted in collaboration with the Rotterdam Study. The authorswould like to thank prof. Dr. Inez de Beaufort (Erasmus MC), Dr.Wim Pinxten (Hasselt University) and Lisa van Bodegom for theircontributions to the project.Compliance with ethical standardsConflict of interest The authors declare that they have no conflictof interests.Human and animal rights This article does not contain any studieswith human participants or animals performed by any of the authors.Open Access This article is distributed under the terms of theCreative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided you giveappropriate credit to the original author(s) and the source, provide alink to the Creative Commons license, and indicate if changes weremade.References1. Vernooij MW, Ikram MA, Tanghe HL, et al. Incidental findingson brain MRI in the general population. N Engl J Med.2007;357(18):1821–8.2. Morris Z, Whiteley WN, Longstreth WT, et al. Incidental find-ings on brain magnetic resonance imaging: systematic review andmeta-analysis. BMJ. 2009;339:b3016.3. Hegenscheid K, Seipel R, Schmidt CO, et al. Potentially relevantincidental findings on research whole-body MRI in the generaladult population: frequencies and management. Eur Radiol.2013;23(3):816–26.4. Wolf SM, Lawrenz FP, Nelson CA, et al. Managing incidentalfindings in human subjects research: analysis and recommenda-tions. J Law Med Ethics. 2008;36(2):219–48.5. Merriam-Webster.com 2015. http://www.merriam-webster.com.1 December 2015.6. Presidential Commission for the Study of Bioethical Issues.Anticipate and Communicate: Ethical Management of Incidentaland Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts. Presidential Commission for the Study ofBioethical Issues. 2013.7. Representatives of Research Imaging Centres, ProfessionalSocieties, Regulatory Bodies, Funding Organisations, RoyalColleges involved in research imaging and Patient Organisations,in the UK. Management of Incidental Findings Detected DuringResearch Imaging. London: SINAPSE and the Royal College ofRadiologists. 2011.8. Nelson CA. Incidental findings in magnetic resonance imaging(MRI) brain research. J Law Med Ethics. 2008;36(2):315–9.9. Petersen SE, Matthews PM, Bamberg F, et al. Imaging in pop-ulation science: cardiovascular magnetic resonance in 100,000participants of UK Biobank-rationale, challenges and approaches.J Cardiovasc Magn Reson. 2013;15:46.10. Bamberg F, Kauczor HU, Weckbach S, et al. Whole-body MRimaging in the German National Cohort: rationale, design, andtechnical background. Radiology. 2015;277(1):206–20.11. Reneman L, de Win MML, Booij J, et al. Incidental head andneck findings on MRI in young healthy volunteers: prevalenceand clinical implications. Am J Neuroradiol. 2012;33(10):1971–4.12. Cieszanowski A, Maj E, Kulisiewicz P, et al. Non-contrast-en-hanced whole-body magnetic resonance imaging in the generalpopulation: the incidence of abnormal findings in patients50 years old and younger compared to older subjects. PLoS One.2014;9(9):e107840.13. Royal JM, Peterson BS. The risks and benefits of searching forincidental findings in MRI research scans. J Law Med Ethics.2008;36(2):305–14.14. Orme NM, Fletcher JG, Siddiki HA, et al. Incidental findings inimaging research: evaluating incidence, benefit, and burden. ArchIntern Med. 2010;170(17):1525–32.15. Grossman RI, Bernat JL. Incidental research imaging findings:Pandora’s costly box. Neurology. 2004;62(6):849–50.16. Miller FG, Mello MM, Joffe S. Incidental findings in humansubjects research: what do investigators owe research partici-pants? J Law Med Ethics. 2008;36(2):271.17. Kirschen MP, Jaworska A, Illes J. Subjects’ expectations inneuroimaging research. J Magn Reson Imaging. 2006;23(2):205–9.18. Mamourian A. Incidental findings on research functional MRimages: Should we look? Am J Neuroradiol. 2004;25(4):520–2.19. Illes J, Kirschen MP, Edwards E, et al. Practical approaches toincidental findings in brain imaging research. Neurology.2008;70(5):384–90.20. Schmidt CO, Hegenscheid K, Erdmann P, et al. Psychosocialconsequences and severity of disclosed incidental findings fromwhole-body MRI in a general population study. Eur Radiol.2013;23(5):1343–51.21. Booth TC, Jackson A, Wardlaw JM, Taylor SA, Waldman AD.Incidental findings found in ‘‘healthy’’ volunteers during imagingperformed for research: current legal and ethical implications. BrJ Radiol. 2010;83(990):456–65.22. Shoemaker JM, Holdsworth MT, Aine C, et al. A practicalapproach to incidental findings in neuroimaging research. Neu-rology. 2011;77(24):2123–7.4 E. M. Bunnik, M. W. Vernooij123

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Incidental findings in population imaging revisited

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Incidental findings in population imaging revisited

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