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Preview Quantile Regression in Clinical Research: Complete analysis for data at a loss of homogeneity

Ton J. Cleophas Aeilko H. Zwinderman Quantile Regression in Clinical Research Complete analysis for data at a loss of homogeneity Quantile Regression in Clinical Research (cid:129) Ton J. Cleophas Aeilko H. Zwinderman Quantile Regression in Clinical Research Complete analysis for data at a loss of homogeneity TonJ.Cleophas AeilkoH.Zwinderman AlbertSchweitzerHospital Dept.BiostatisticsandEpidemiology DepartmentMedicine AcademicMedicalCenter SLIEDRECHT,Zuid-Holland, Amsterdam,TheNetherlands TheNetherlands ISBN978-3-030-82839-4 ISBN978-3-030-82840-0 (eBook) https://doi.org/10.1007/978-3-030-82840-0 ©TheEditor(s)(ifapplicable)andTheAuthor(s),underexclusivelicensetoSpringerNatureSwitzerland AG2021 Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similarordissimilarmethodologynowknownorhereafterdeveloped. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthispublication doesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevant protectivelawsandregulationsandthereforefreeforgeneraluse. The publisher, the authors, and the editorsare safeto assume that the adviceand informationin this bookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernortheauthorsor theeditorsgiveawarranty,expressedorimplied,withrespecttothematerialcontainedhereinorforany errorsoromissionsthatmayhavebeenmade.Thepublisherremainsneutralwithregardtojurisdictional claimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface ExceptforWiley’seditionofQuantileRegression:EstimationandSimulation,vol 1 (2017) and vol 2 (2020), by the Italian econometrists from Naples University, FurnoandVistocci,notextbookshavebeenpublishedthataddressclinicalresearch. Quantileregressionisanapproachtodataatalossofhomogeneity,forexample: 1. Datawithoutliers 2. Skeweddatalikecorona-deathsdata 3. Datawithinconstantvariability 4. Bigdata Inclinicalresearch,manyexamplescanbegivenlikecircadianphenomena,and the spread of diseases may be dependent on subsets with frailty, low weight, poor hygiene,andmanyformsoflackofhealthiness.Stratifiedanalysisisalaboriousand rather explorative way of analysis, but quantile analysis may be a more fruitful, quicker,andmorecompletealternative forthepurpose.Consideringallofthis,we are on the verge of a revolution in data analysis that has begun with the tentative acceptanceofmultiplepredictorvariablesinprospectiverandomizedresearchandis now with “Koenker’s Quantile regression R package version 5.05 2013”and “le Cook’s Thinking beyond the mean” (Sjanghai Arch Psychiatr 2013, pp. 55–59) definitive. The current edition is the first textbook and tutorial of quantile regressions for medicalandhealthcarestudentsaswellasrecollection/updatebenchandhelpdesk forprofessionals.Eachchaptercanbestudiedasastandaloneandcoversoneofthe manyfieldsinthefast-growingworldofquantileregressions.Step-by-stepanalyses ofover 20data files stored atextras.springer.com areincludedfor self-assessment. We should add that the authors are well qualified in their field. Professor Zwinderman is past president of the International Society of Biostatistics (2012– 2015) and Professor Cleophas is past president of the American College of Angiology(2000–2002).Fromtheirexpertise,theyshouldbeabletomakeadequate selections of modern quantile regression methods for the benefit of physicians, v vi Preface students,andinvestigators.Theauthorshavebeenworkingandpublishingtogether for 22 years, and their research can be characterized as a continued effort to demonstrate that clinical data analysis is not mathematics but rather a discipline at theinterfaceofbiologyandmathematics. Sliedrecht,Zuid-Holland, TonJ.Cleophas TheNetherlands Amsterdam,TheNetherlands AeilkoH.Zwinderman Contents 1 GeneralIntroduction. . . . . . . . .. . . . . . . .. . . . . . . . .. . . . . . . . .. 1 1.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 PrincipleofRegressionAnalysis. . . . . . . . . . . . . . . . . . . . . . . 3 1.4 PrincipleofQuantileRegression. . . . . . . . . . . . . . . . . . . . . . . 4 1.5 HistoryandBackgroundofQuantileRegression. . . . . . . . . . . . 5 1.6 DataExample. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.7 SeparatingQuantiles,TraditionalandQuantile-wise. . . . . . . . . 6 1.8 SpecialCase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1.9 QuantileRegressionBothforContinuousandDiscrete OutcomeVariables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1.10 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2 MathematicalModelsforSeparatingQuantiles fromOneAnother. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.3 MaximizingLinearFunctionswiththeHelp ofSupportVectors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.4 LagrangianMultiplierMethod. . . . . . . . . . . . . . . . . . . . . . . . . 11 2.5 MaximizingLinearFunctionswiththeHelpofRectangles. . . . . 12 2.6 MaximizingLinearFunctionswiththeHelpofSimplex Algorithms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.7 TheIntuitionofQuantileRegression. . . . . . . . . . . . . . . . . . . . 15 2.8 SpecialCase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.9 TraditionalStatisticalMethodsAppliedinThisEdition. . . . . . . 17 2.10 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.11 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 vii viii Contents PartI SimpleUnivariateRegressionsVersusQuantile 3 TraditionalandRobustRegressionsVersusQuantile. . . . . . . . . . . 23 3.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.3 TraditionalandRobustRegression. . . . . . . . . . . . . . . . . . . . . . 25 3.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 3.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4 AutocorrelationsVersusQuantileRegressions. . . . . . . . . . . . . . . . 35 4.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.3 AutoregressionAnalysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 4.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.5 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 4.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5 DiscreteTrendTestingVersusQuantileRegression. . . . . . . . . . . . 45 5.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.3 DiscreteTrendAnalysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 6 ContinuousTrendTestingVersusQuantileRegression. . . . . . . . . . 51 6.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 6.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 6.3 LinearTrendTestingofContinuousData. . . . . . . . . . . . . . . . . 52 6.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 6.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 6.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 7 BinaryPoisson/NegativeBinomialRegressionsVersusQuantile. . . 59 7.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 7.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 7.3 BinaryPoissonandNegativeBinomialRegressions. . . . . . . . . 60 7.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 7.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 7.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 8 RobustStandardErrorsRegressionsVersusQuantile. . . . . . . . . . 69 8.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 8.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 8.3 RobustStandardErrors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 8.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Contents ix 8.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 8.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 9 OptimalScalingVersusQuantileRegression. . . . . . . . . . . . . . . . . . 75 9.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 9.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 9.3 OptimalScaling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 9.4 QuantileRegression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 9.5 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 9.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 10 InterceptonlyPoissonRegressionVersusQuantile. . . . . . . . . . . . . 83 10.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 10.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 10.3 PoissonInterceptOnly. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 10.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 10.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 10.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 PartII MultipleVariablesRegressionsVersusQuantile 11 FourPredictorsRegressionsVersusQuantile. . . . . . . . . . . . . . . . . 91 11.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 11.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 11.3 FourPredictorsRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . 93 11.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 11.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 11.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 12 GeneExpressionsRegressions,TraditionalVersusQuantile. . . . . . 103 12.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 12.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 12.3 GeneExpressionsRegression. . . . . . . . . . . . . . . . . . . . . . . . . 104 12.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 12.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 12.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 13 Koenker’sMultipleVariablesAnalysiswithQuantileModeling. . . 113 13.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 13.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 13.3 SASStatisticalSoftwareGraphsInterpreted. . . . . . . . . . . . . . . 114 13.4 FirstFourGraphs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 13.5 TheSecondSetofFourGraphs. . . . . . . . . . . . . . . . . . . . . . . . 116 13.6 TheThirdSetofFourGraphs. . . . . . . . . . . . . . . . . . . . . . . . . 117 13.7 TheFourthSetofFourGraphs. . . . . . . . . . . . . . . . . . . . . . . . 118 13.8 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 13.9 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 x Contents 14 InteractionAdjustedRegressionVersusQuantile. . . . . . . . . . . . . . 121 14.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 14.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 14.3 InteractionAdjustedRegression. . . . . . . . . . . . . . . . . . . . . . . . 122 14.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 14.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 14.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 15 QuantileRegressiontoStudyCoronaDeaths. . . . . . . . . . . . . . . . . 131 15.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 15.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 15.3 MethodsandMainResults. . . . . . . . . . . . . . . . . . . . . . . . . . . 132 15.4 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 15.5 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 16 LaboratoryValuesPredictSurvivalSepsis,Traditional RegressionVersusQuantile. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 16.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 16.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 16.3 TraditionalRegression. . . . .. . . . . . . .. . . . . . . .. . . . . . . .. . 138 16.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 16.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 16.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 17 MultinomialRegressionVersusQuantile. . . . .. . . . . . . .. . . . . . .. 151 17.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 17.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 17.3 MultinomialRegressionsandMore. . . . . . . . . . . . . . . . . . . . . 153 17.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 17.5 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 17.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 18 RegressionswithInconstantVariability,Traditional andWeightedLeastSquaresAnalysisVersusQuantile. . . . . . . . . . 165 18.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 18.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 18.3 RegressionswithInconstantVariability. . . . . . . . . . . . . . . . . . 167 18.4 QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 18.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 18.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 19 RestructuringCategoriesintoMultipleBinaryVariablesVersus QuantileRegressions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 19.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 19.2 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 19.3 TraditionalMultipleRegressionAfterRestructuring PredictiveCategoriesintoMultipleBinaryVariables. . . . . . . . . 176

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