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Medical Decision Making Medical Decision Making SecondEdition Harold C. Sox, M.D. GeiselSchoolofMedicineatDartmouth,Hanover,NewHampshire Michael C. Higgins, Ph.D. StanfordUniversity,Stanford,California Douglas K. Owens, M.D., M.S. DepartmentofVeteransAffairsPaloAltoHealthCareSystem,PaloAlto,California StanfordUniversity,Stanford,California A John Wiley & Sons, Ltd., Publication Thiseditionfirstpublished2013,©2013byJohnWiley&Sons,Ltd. Firsteditionpublished1988©1988ButterworthPublishers,Stoneham,MA,USA Wiley-BlackwellisanimprintofJohnWiley&Sons,formedbythemergerofWiley’sglobalScientific, TechnicalandMedicalbusinesswithBlackwellPublishing. Registeredoffice:JohnWiley&Sons,Ltd,TheAtrium,SouthernGate,Chichester, WestSussex,PO198SQ,UK Editorialoffices:9600GarsingtonRoad,Oxford,OX42DQ,UK TheAtrium,SouthernGate,Chichester,WestSussex,PO198SQ,UK 111RiverStreet,Hoboken,NJ07030-5774,USA Fordetailsofourglobaleditorialoffices,forcustomerservicesandforinformationabouthowtoapply forpermissiontoreusethecopyrightmaterialinthisbookpleaseseeourwebsiteat www.wiley.com/wiley-blackwell. Therightoftheauthorstobeidentifiedastheauthorsofthisworkhasbeenassertedinaccordancewith theUKCopyright,DesignsandPatentsAct1988. Allrightsreserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,or transmitted,inanyformorbyanymeans,electronic,mechanical,photocopying,recordingorotherwise, exceptaspermittedbytheUKCopyright,DesignsandPatentsAct1988,withoutthepriorpermissionof thepublisher. Designationsusedbycompaniestodistinguishtheirproductsareoftenclaimedastrademarks.Allbrand namesandproductnamesusedinthisbookaretradenames,servicemarks,trademarksorregistered trademarksoftheirrespectiveowners.Thepublisherisnotassociatedwithanyproductorvendor mentionedinthisbook.Thispublicationisdesignedtoprovideaccurateandauthoritativeinformation inregardtothesubjectmattercovered.Itissoldontheunderstandingthatthepublisherisnotengaged inrenderingprofessionalservices.Ifprofessionaladviceorotherexpertassistanceisrequired,the servicesofacompetentprofessionalshouldbesought. Thecontentsofthisworkareintendedtofurthergeneralscientificresearch,understanding,and discussiononlyandarenotintendedandshouldnotberelieduponasrecommendingorpromotinga specificmethod,diagnosis,ortreatmentbyhealthsciencepractitionersforanyparticularpatient.The publisherandtheauthormakenorepresentationsorwarrantieswithrespecttotheaccuracyor completenessofthecontentsofthisworkandspecificallydisclaimallwarranties,includingwithout limitationanyimpliedwarrantiesoffitnessforaparticularpurpose.Inviewofongoingresearch, equipmentmodifications,changesingovernmentalregulations,andtheconstantflowofinformation relatingtotheuseofmedicines,equipment,anddevices,thereaderisurgedtoreviewandevaluatethe informationprovidedinthepackageinsertorinstructionsforeachmedicine,equipment,ordevicefor, amongotherthings,anychangesintheinstructionsorindicationofusageandforaddedwarningsand precautions.Readersshouldconsultwithaspecialistwhereappropriate.Thefactthatanorganizationor Websiteisreferredtointhisworkasacitationand/orapotentialsourceoffurtherinformationdoesnot meanthattheauthororthepublisherendorsestheinformationtheorganizationorWebsitemayprovide orrecommendationsitmaymake.Further,readersshouldbeawarethatInternetWebsiteslistedinthis workmayhavechangedordisappearedbetweenwhenthisworkwaswrittenandwhenitisread.No warrantymaybecreatedorextendedbyanypromotionalstatementsforthiswork.Neitherthepublisher northeauthorshallbeliableforanydamagesarisingherefrom. LibraryofCongressCataloging-in-PublicationData Sox,HaroldC. Medicaldecisionmaking/HaroldC.Sox,MichaelC.Higgins,DouglasK.Owens.--2nded. p.;cm. Rev.ed.of:Medicaldecisionmaking/HaroldC.Sox,Jr....[etal.].c1998. Includesbibliographicalreferencesandindex. Summary:‘‘Thistitleprovidesathoroughunderstandingofthekeydecisionmakinginfrastructureof clinicalpracticeandretainsitsemphasisonpracticeandprinciplesofindividualizedmedicaldecision making’’–Providedbypublisher. ISBN978-0-470-65866-6(paper) I.Higgins,MichaelC.(MichaelClark),1950-II.Owens,DouglasK.III.Medicaldecisionmaking.IV. Title. [DNLM:1. Diagnosis,Differential.2. Cost-BenefitAnalysis.3. DecisionMaking.4. Probability. WB141.5] (cid:2) 616.075–dc23 2012047951 AcataloguerecordforthisbookisavailablefromtheBritishLibrary. Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsinprintmay notbeavailableinelectronicbooks. CoverdesignbyRobSawkinsforOptaDesignLtd. Setin9.5/12ptPalatinobyLaserwordsPrivateLimited,Chennai,India 12013 ToJeanandKathleen ToSara,Rachel,andChristopher ToCarol,Colin,andLara Theirsupporthasmeanteverything. Contents Foreword,xi Preface,xv 1 Introduction,1 1.1 HowmayIbethoroughyetefficientwhenconsideringthepossible causesofmypatient’sproblems?1 1.2 How do I characterize the information I have gathered during the medicalinterviewandphysicalexamination?2 1.3 HowdoIinterpretnewdiagnosticinformation?5 1.4 HowdoIselecttheappropriatediagnostictest?5 1.5 HowdoIchooseamongseveralriskytreatmentalternatives?6 1.6 Summary,6 2 Differentialdiagnosis,7 2.1 Introduction,7 2.2 Howcliniciansmakeadiagnosis,8 2.3 Theprinciplesofhypothesis-drivendifferentialdiagnosis,11 2.4 Anextendedexample,21 Bibliography,26 3 Probability:quantifyinguncertainty,27 3.1 Uncertaintyandprobabilityinmedicine,27 3.2 Usingpersonalexperiencetoestimateprobability,34 3.3 Usingpublishedexperiencetoestimateprobability,46 3.4 Taking the special characteristics of the patient into account when estimatingprobability,57 Problems,58 Bibliography,59 4 Understandingnewinformation:Bayes’theorem,61 4.1 Introduction,61 4.2 Conditionalprobabilitydefined,64 4.3 Bayes’theorem,65 4.4 TheoddsratioformofBayes’theorem,69 4.5 LessonstobelearnedfromBayes’theorem,76 4.6 TheassumptionsofBayes’theorem,82 4.7 UsingBayes’theoremtointerpretasequenceoftests,84 vii viii Contents 4.8 UsingBayes’theoremwhenmanydiseasesareunder consideration,88 Problems,90 Bibliography,91 5 Measuringtheaccuracyofdiagnosticinformation,93 5.1 How to describe test results: abnormal and normal, positive and negative,93 5.2 Measuringatest’scapabilitytorevealthepatient’struestate,98 5.3 Howtomeasurethecharacteristicsofadiagnostictest:ahypothetical case,106 5.4 Pitfallsofpredictivevalue,109 5.5 Sources of biased estimates of test performance and how to avoid them,110 5.6 Spectrumbias,116 5.7 Expressingtestresultsascontinuousvariables,125 5.8 Combiningdatafromseveralstudiesoftestperformance,134 Problems,137 Bibliography,140 6 Expectedvaluedecisionmaking,143 6.1 Anexample,145 6.2 Selectingthedecisionmaker,148 6.3 Decisiontrees:structuredrepresentationsfordecisionproblems,149 6.4 Quantifyinguncertainty,152 6.5 Probabilisticanalysisofdecisiontrees,156 6.6 Expectedvaluecalculations,158 6.7 Sensitivityanalysis,161 6.8 Foldingbackdecisiontrees,163 Problems,168 Bibliography,168 7 Markovmodelsandtime-varyingoutcomes,170 7.1 Markovmodelbasics,170 7.2 Exponentialsurvivalmodelandlifeexpectancy,189 Problems,198 Appendix:Mathematicaldetails,200 Bibliography,203 8 Measuringtheoutcomeofcare–expectedutilityanalysis,204 8.1 Basicconcept–directutilityassessment,205 8.2 Sensitivityanalysis–testingtherobustnessofutilityanalysis,210 8.3 Shortcut–usingalinearscaletoexpressstrengthofpreference,212 8.4 Exponentialutility–aparametricmodel,213 8.5 Exponentialutilitywithexponentialsurvival,218 Contents ix 8.6 Multidimensionaloutcomes–directassessment,220 8.7 Multidimensionaloutcomes–simplifications,223 8.8 Multidimensionaloutcomes–quality-adjustedlifeyears (QALY),228 8.9 Comparison of the two models for outcomes with different length andquality,232 Problems,235 Appendix:Mathematicaldetails,237 Bibliography,242 9 Selectionandinterpretationofdiagnostictests,243 9.1 Takingactionwhentheconsequencesareuncertain:principlesand definitions,244 9.2 Thetreatment-thresholdprobability,247 9.3 Thedecisiontoobtainadiagnostictest,252 9.4 Choosingbetweendiagnostictests,259 9.5 Choosingthebestcombinationofdiagnostictests,261 9.6 Settingthetreatment-thresholdprobability,263 9.7 Takingaccountoftheutilityofexperiencingatest,275 9.8 Aclinicalcase:testselectionforsuspectedbraintumor,279 9.9 Sensitivityanalysis,281 Bibliography,287 10 Cost-effectivenessanalysisandcost–benefitanalysis,288 10.1 Theclinician’sconflictingroles:patientadvocate,memberofsociety, andentrepreneur,288 10.2 Cost-effectiveness analysis: a method for comparing management strategies,291 10.3 Cost–benefit analysis: a method for measuring the net benefit of medicalservices,298 10.4 Measuringthecostsofmedicalcare,301 Problems,304 Bibliography,305 11 Medicaldecisionanalysisinpractice:advancedmethods,307 11.1 Anoverviewofadvancedmodelingtechniques,307 11.2 Useofmedicaldecision-makingconceptstoanalyzeapolicy problem:thecost-effectivenessofscreeningforHIV,311 11.3 Useofmedicaldecision-makingconceptstoanalyzeaclinical diagnosticproblem:strategiestodiagnosetumorsinthelung,323 11.4 Useofcomplexmodelsforindividual-patientdecisionmaking,330 Bibliography,333 Index,337 Foreword The maturation of medical science during the last half of the twentieth century was most impressive. Clinical trials displaced observational studies thattypicallyconsistedofadozenorfewerpatients;thepathophysiologyand genetics of many diseases were discovered; and diagnostic and therapeutic methods advanced. Crude diagnostic tests such as cholecystography and barium enemas and risky tests such as air encephalograms,needle biopsies, and exploratory laparotomies were made obsolete by technology. Flexible tubes, some outfitted with lights and cameras, CT, MRI, and PET scanners, and sophisticated immuno-analyses of blood and other body fluids gained immediateacceptance.Manytherapiesthatwereformulatedbygrindingup organs, desiccatingthem, and hoping that they would correct a deficitwere replacedbynew,potentchemicals. Clinicalreasoning,theprocessesbehindbothdiagnosisandmedicaldeci- sionmaking,includingthecomplextradeoffsbetweentherisksandbenefits of tests and treatments, lagged behind advances in medical science. In the run-uptothelastquarterofthecentury,studentslearnedhowtoreasonabout patientproblemsbyobservingexpertcliniciansatwork,and(iftheydared) byaskingthemwhytheyorderedthistestorthat,whytheygaveonedrugor another.Becausethisapprenticeshipapproachwasnotcodified,objectified,or quantified,medicaltextsstruggledtoexplainclinicalreasoning,andstudents struggledtolearnit.Andwhentheevidenceofconfusionabouttheuseoftests andtreatmentsfirstemerged,alarmbellsclanged.Researchershaddiscovered extremevariationsintheuseoftestsandtreatmentsfromonecommunityto anotherandinregionsacrossthecountrywithoutacorrespondingbenefitfor patients.Irrationaltestingandtreatinghadbeguntocontributesubstantially toanimpossibleescalationinthecostofcare. Duringthelastthreedecadesofthetwentiethcentury,clinician–scientists begantoexaminetheprocessesofdiagnosisanddecisionmakingwithtools from other disciplines, including cognitive science, decision science, proba- bility, and utility theory. From these diverse sources the clinical science of medical decision making was hatched. Elements of the diagnostic process were identified and a language for explaining and teaching diagnosis was formulated. Cognitive errors in diagnosis were sought and methods devel- opedtoavoidthem.Thecriticalimportanceofaprobabilisticrepresentation of diagnosis, in terms of prior probabilities, conditional probabilities, and likelihoodratios,wasrecognizedandputtouseintheformofacenturies-old formulation of Bayes’ Rule. Decision analysis, a discipline formerly used by themilitary,wasappliedfirsttoindividualclinicalproblems,latertoclassesof xi xii Foreword problems,andeventuallytoissuesofcostandefficacyoftestsandtreatments. Beforetheendofthetwentiethcentury,ascienceofmedicaldecisionmaking andalanguageforteachingithadbeenborn. Implementingthenewscience,however,provedmoredifficultthandevel- opingit.Skepticsaverredthatphysicians’estimatesofprobabilitieswereoften flawed,thatapplyingBayes’Rulewasnoteasy,andthatdecisiontreeswere eithertoosimple(andthusdidnotrepresentaclinicalproblemsufficiently) ortoocomplex(andthuscouldnotbeunderstood).Manywonderedwhether medicinecouldbeconvincedtoadoptthesenewapproachesandwhetherthe averagephysiciancouldbeexpectedtousethemintheirday-to-daypractices. As the field has evolved, some of these questions have been answered. Now, in the second decade of the twenty-first century, Bayes’ Rule is used to design clinical trials, to develop decision rules that help physicians judge whethertoadmitpatientssuspectedofhavinganacutemyocardialinfarction, and to develop compiled strategies for diagnosing and treating pulmonary emboli, to name a few applications. Decision analysis has been used to formulate answers for individual patients’ dilemmas, but this use is time consuming, expensive, and requires special expertise. Nonetheless, decision analysishasfoundextensiveapplicationinclinicalpracticeguidelinedevelop- ment,cost-effectiveanalyses,andcomparativeeffectivenessstudies.Acadre of physicians has become sufficiently skilled in the methods to apply them in active clinical teaching environments and to integrate them into medical studentandresidencycurricula. It is legitimate to ask why a student or resident should spend the intel- lectual capital to learn these methods. The answer is compelling. First, they help in learning and teaching the process of diagnosis. Second, the princi- ples of screening and diagnostic and management decision making become transparentfromanunderstandingofBayes’Rule,diagnosticandtherapeutic thresholds,decisionaltoss-ups,anddecisionanalysis.Subjectingsuchissues torationalexaminationimprovesdecisionmakingand,consequently,patient care.Moreover,becausethesemethodsarethebasisforsomanyanalysesof health practices, appreciation of their limitations provides a healthy skepti- cism of their applications. Lastly, the approaches are powerful tools to pass on the concepts to others, as well as critical templates to understand honest differencesofopiniononcontroversialmedicalpractices. Forthepast25years,MedicalDecisionMakinghasbeenanidealvenuefor developing a rich comprehension of these methods and for understanding howtoapproachdiagnosis;thenewsecondeditionisevenbetter.Itschapter onBayes’Rule,forexample,isexemplary,explainingthemethodinmultiple different formats. The chapters on selection of diagnostic tests and decision analysis are meticulously crafted so as to leave little uncertainty about the methods.Anewchapteronmodelingmethodsisrichlyillustratedbyactual analyses;thechaptersonexpectedvaluedecisionmaking,utilityassessment, andMarkovmodelinghavebeenextensivelyrevised. Foreword xiii In short, this book has been a standard of the field, and the new edition will continue its dominance. There is little doubt that in the future many clinical analyses will be based on the methods described in Medical Decision Making,andthebookprovidesabasisforacriticalappraisalofsuchpolicies. Teachersofmedicaldecisionmakingwillrequireit;medicalstudentswilldig intoitrepeatedlyastheylearnclinicalmedicine;residentswillgobacktoit again and again to refresh their diagnostic and therapeutic skills. And from itslucidpages,practicingphysicianswillattainaricherunderstandingofthe principlesunderlyingtheirwork. JeromeP.Kassirer,M.D. DistinguishedProfessor,TuftsUniversitySchoolofMedicine,US VisitingProfessor,StanfordMedicalSchool,US

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Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.