Design and Analysis of Experiments in the Health Sciences

238 Pages·2012·3.872 MB·English

by  Gerald van Belle, Kathleen F. Kerr(auth.)

DESIGN AND ANALYSIS OF
EXPERIMENTS IN
THE HEALTH SCIENCES
DESIGN AND ANALYSIS
OF EXPERIMENTS IN
THE HEALTH SCIENCES
Gerald van Belle
SchoolofPublicHealth
TheUniversityofWashington
Seattle,WA
Kathleen F. Kerr
SchoolofPublicHealth
TheUniversityofWashington
Seattle,WA
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LibraryofCongressCataloging-in-PublicationData:
VanBelle,Gerald.
Designandanalysisofexperimentsinthehealthsciences/Geraldvan
Belle,KathleenF.Kerr.—1sted.
p.cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-12727-8(hardback)
1. Medicalinformatics. 2. Medicalsciences—Statisticalmethods.
3. Experimentaldesign. I. Kerr,KathleenF.,1970– II. Title.
R858.V36 2012
610.72(cid:2)7—dc23
2011044306
PrintedintheUnitedStatesofAmerica
10987654321
GvB:ForWestAfricanVocationalSchools(WAVS)
KK:ForAlexandEve
CONTENTS
Preface xiii
1 TheBasics 1
1.1 FourBasicQuestions / 1
1.2 Variation / 4
1.3 PrinciplesofDesignandAnalysis / 5
1.4 ExperimentsandObservationalStudies / 9
1.5 IllustrativeApplicationsofPrinciples / 11
1.6 ExperimentsintheHealthSciences / 12
1.7 AdaptiveAllocation / 15
1.7.1 Equidistribution / 15
1.7.2 AdaptiveAllocationTechniques / 16
1.8 SampleSizeCalculations / 18
1.9 StatisticalModelsfortheData / 20
1.10 AnalysisandPresentation / 22
1.10.1 GraphtheDatainSeveralWays / 22
1.10.2 AssessAssumptionsoftheStatisticalModel / 22
1.10.3 ConfirmatoryandExploratoryAnalysis / 23
1.10.4 MissingDataNeedCarefulAccounting / 23
1.10.5 StatisticalSoftware / 24
1.11 Notes / 24
1.11.1 CharacterizationStudies / 24
1.11.2 AdditionalCommentsonBalance / 25
1.11.3 LinearandNonlinearModels / 25
1.11.4 AnalysisofVarianceVersusRegressionAnalysis / 26
1.12 Summary / 26
1.13 Problems / 26
vii
viii CONTENTS
2 CompletelyRandomizedDesigns 31
2.1 Randomization / 31
2.2 HypothesesandSampleSize / 32
2.3 EstimationandAnalysis / 32
2.4 Example / 34
2.5 DiscussionandExtensions / 36
2.5.1 PreparingDataforComputerAnalysis / 36
2.5.2 TreatmentAssignmentinthisExample / 37
2.5.3 CheckonRandomization / 37
2.5.4 PartitioningtheTreatmentSumofSquares / 37
2.5.5 AlternativeEndpoints / 38
2.5.6 DummyVariables / 38
2.5.7 Contrasts / 39
2.6 Randomization / 41
2.7 HypothesesandSampleSize / 41
2.8 EstimationandAnalysis / 41
2.9 Example / 42
2.10 DiscussionandExtensions / 44
2.10.1 TwoRolesforANCOVA / 44
2.10.2 PartitioningofSumsofSquares / 45
2.10.3 AssumptionofParallelism / 46
2.11 Notes / 47
2.11.1 ConstrainedRandomization / 47
2.11.2 AssumptionsoftheAnalysisofVarianceand
Covariance / 48
2.11.3 WhentheAssumptionsDon’tHold / 49
2.11.4 AlternativeGraphicalDisplays / 50
2.11.5 SampleSizesforMoreThanTwoLevels / 51
2.11.6 LimitationsofComputerOutput / 51
2.11.7 UnequalSampleSizes / 51
2.11.8 DesignImplicationsoftheCRD / 51
2.11.9 PowerandAlternativeHypotheses / 52
2.11.10 RegressionorAnalysisofVariance? / 52
2.11.11 Bioassay / 52
2.12 Summary / 53
2.13 Problems / 53
3 RandomizedBlockDesigns 63
3.1 Randomization / 64
3.2 HypothesesandSampleSize / 64
CONTENTS ix
3.3 EstimationandAnalysis / 64
3.4 Example / 65
3.5 DiscussionandExtensions / 67
3.5.1 EvaluatingModelAssumptions / 67
3.5.2 MultipleComparisons / 69
3.5.3 NumberofTreatmentsandBlockSize / 71
3.5.4 MissingData / 71
3.5.5 DoesItAlwaysPaytoBlock? / 71
3.5.6 ConcomitantVariables / 72
3.5.7 Imbalance / 74
3.6 Randomization / 77
3.7 HypothesesandSampleSize / 77
3.8 EstimationandAnalysis / 77
3.9 Example / 77
3.10 DiscussionandExtensions / 79
3.10.1 ImplicationsoftheModel / 79
3.10.2 NumberofLatinSquares / 79
3.11 Randomization / 80
3.12 HypothesesandSampleSize / 81
3.13 EstimationandAnalysis / 82
3.14 Example / 82
3.15 DiscussionandExtensions / 85
3.15.1 PartiallyBalancedIncompleteBlockDesigns / 85
3.16 Notes / 86
3.16.1 AnalysisFollowsDesign / 86
3.16.2 RelativeEfficiency / 86
3.16.3 AdditivityoftheModel / 87
3.17 Summary / 88
3.18 Problems / 88
4 FactorialDesigns 93
4.1 Randomization / 95
4.2 HypothesesandSampleSize / 95
4.3 EstimationandAnalysis / 96
4.4 Example1 / 97
4.5 Example2 / 100
4.6 Notes / 103
4.6.1 RegressionAnalysisApproaches / 103
4.6.2 AlmostFactorial / 105
x CONTENTS
4.6.3 DesignStructureandFactorStructure / 105
4.6.4 EffectandInteractionTables / 105
4.6.5 BalancedDesign / 105
4.6.6 MissingData / 106
4.6.7 Fixed,Random,andMixedEffectsModels / 106
4.6.8 FractionalFactorials / 108
4.7 Summary / 109
4.8 Problems / 110
5 MultilevelDesigns 117
5.1 Randomization / 118
5.2 HypothesesandSampleSize / 118
5.3 EstimationandAnalysis / 119
5.4 Example / 121
5.5 DiscussionandExtensions / 127
5.5.1 Whole-PlotandSplit-PlotVariability / 127
5.5.2 GettingtheComputertoDotheRightAnalysis / 128
5.6 Notes / 129
5.6.1 FractionalFactorials—Example / 129
5.6.2 MissingData / 129
5.7 Summary / 130
5.8 Problems / 130
6 RepeatedMeasuresDesigns 135
6.1 Randomization / 136
6.2 HypothesesandSampleSize / 136
6.3 EstimationandAnalysis / 137
6.4 Example / 139
6.5 DiscussionandExtensions / 142
6.6 Notes / 143
6.6.1 RBDandRMD / 143
6.6.2 MissingData:TheFundamentalChallengeinRMD / 143
6.6.3 CorrelationStructure / 144
6.6.4 DerivedVariableAnalysis / 144
6.7 Summary / 144
6.8 Problems / 145
CONTENTS xi
7 RandomizedClinicalTrials 149
7.1 Endpoints / 151
7.2 Randomization / 152
7.3 HypothesesandSampleSize / 153
7.4 Follow-Up / 154
7.5 EstimationandAnalysis / 154
7.6 Examples / 155
7.7 DiscussionandExtensions / 159
7.7.1 StatisticalSignificanceandClinicalImportance / 159
7.7.2 Ethics / 161
7.7.3 Reporting / 162
7.8 Notes / 163
7.8.1 MulticenterTrials / 163
7.8.2 InternationalHarmonization / 167
7.8.3 DataSafetyMonitoring / 167
7.8.4 AncillaryStudies / 168
7.8.5 SubgroupAnalysisandDataMining / 168
7.8.6 Meta-Analysis / 169
7.8.7 AuthorshipandRecognition / 169
7.8.8 Communication / 169
7.8.9 DataSharing / 170
7.8.10 N-of-1Trials / 170
7.9 Resources / 171
7.10 Summary / 171
7.11 Problems / 171
8 Microarrays 179
8.1 Introduction / 179
8.2 Genes,GeneExpression,andMicroarrays / 179
8.2.1 GenesandGeneExpression / 179
8.2.2 GeneExpressionMicroarrays / 180
8.3 ExamplesofMicroarrayStudies / 186
8.4 ReplicationandSampleSize / 188
8.5 BlockingandMicroarrays / 189
8.6 RandomizationandMicroarrays / 190
8.7 MicroarrayDataAnalysisIssues / 191
8.7.1 ImageAnalysis / 191
8.7.2 DataPreprocessing / 193
xii CONTENTS
8.7.3 IdentifyingDifferentiallyExpressedGenes / 196
8.7.4 MultipleTesting / 196
8.7.5 GeneSetAnalysis / 198
8.7.6 TheClassPredictionProblem / 198
8.8 DataAnalysisExample / 200
8.9 Notes / 202
8.9.1 SampleSize / 202
8.9.2 FDREstimation / 202
8.9.3 EvaluationofDataPreprocessingMethods / 203
8.10 Summary / 203
8.11 Problems / 203
Bibliography 207
AuthorIndex 217
SubjectIndex 223