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016			_a
020			_a9781119524649
020			_a9781119524656 _qelectronic book
020			_a1119524652 _qelectronic book
020			_a9781119524687 _qelectronic book
020			_a1119524687 _qelectronic book
020			_a9781119524670 _qelectronic publication
020			_a1119524679
020			_z9781119524649 _qpaperback
024	7		_a10.1002/9781119524687 _2doi
035			_a(OCoLC)1198988697 _z(OCoLC)1254088976
040			_aDLC _beng _erda _epn _cDLC _dOCLCO _dOCLCA _dDG1 _dOCLCO _dOCLCF _dOCLCQ _dYDX _dOCLCO
041			_aeng
042			_apcc
050	0	4	_aR853.C55 _bM337 2021
060		4	_aW 20.55.C5
082	0	0	_a610.72/4 _223
100	1		_aMachin, David, _d1939- _0http://id.loc.gov/authorities/names/no2006063962 _eauthor.
245	1	0	_aRandomised clinical trials : _bdesign, practice and reporting / _cDavid Machin, Peter M. Fayers, Bee Choo Tai.
250			_aSecond edition.
264		1	_aHoboken, NJ : _bWiley Blackwell, _c2021.
300			_a1 online resource (xiv, 536 pages)
336			_atext _btxt _2rdacontent.
337			_acomputer _bc _2rdamedia.
338			_aonline resource _bcr _2rdacarrier.
340			_2rdacc _0http://rdaregistry.info/termList/RDAColourContent/1003.
504			_aIncludes bibliographical references and index.
505	0		_aTable of Contents Preface xiii Part I Basic Considerations 1 1 Introduction 3 1.1 Introduction 3 1.2 Some completed trials 4 1.3 Choice of design 13 1.4 Practical constraints 18 1.5 Influencing clinical practice 20 1.6 History 20 1.7 How do trials arise? 22 1.8 Ethical considerations 24 1.9 Regulatory requirements 24 1.10 Focus 25 1.11 Further reading 25 2 Design Features 27 2.1 Introduction 27 2.2 The research question 29 2.3 Patient selection 30 2.4 The consent process 32 2.5 Choice of interventions 33 2.6 Choice of design 35 2.7 Assigning the interventions 37 2.8 Making the assessments 38 2.9 Analysis and reporting 38 2.10 Technical details 42 2.11 Guidelines 43 2.12 Further reading 44 3 The Trial Protocol 45 3.1 Introduction 45 3.2 Abstract 47 3.3 Background 49 3.4 Research objectives 49 3.5 Design 52 3.6 Intervention details 53 3.7 Eligibility 56 3.8 Randomisation 58 3.9 Assessment and data collection 61 3.10 Statistical considerations 63 3.11 Ethical issues 66 3.12 Organisational structure 69 3.13 Publication policy 69 3.14 Trial forms 70 3.15 Appendices 71 3.16 Regulatory requirements 72 3.17 Guidelines 74 3.18 Protocols 74 4 Measurement and Data Capture 77 4.1 Introduction 77 4.2 Types of measures 78 4.3 Measures and endpoints 80 4.4 Making the observations 91 4.5 Baseline measures 92 4.6 Data recording 93 4.7 Technical notes 101 4.8 Guidelines 101 5 Randomisation 103 5.1 Introduction 103 5.2 Rationale 104 5.3 Mechanics 104 5.4 Application 113 5.5 Carrying out randomisation 115 5.6 Documentation 119 5.7 Unacceptable methods 120 5.8 Guidelines 120 6 Trial Initiation 121 6.1 Introduction 121 6.2 Trial organisation 122 6.3 Data collection and processing 130 6.4 Internal data monitoring 132 6.5 Ethical and regulatory requirements 133 6.6 Launching the trial 134 6.7 Trial registries 134 6.8 Guidelines 135 7 Trial Conduct and Completion 137 7.1 Introduction 137 7.2 Regular feedback 137 7.3 Publicity 141 7.4 Protocol modifications 142 7.5 Preparing the publication(s) 142 7.6 The next trial? 145 7.7 Protocol 146 8 Basics for Analysis 147 8.1 Introduction 147 8.2 The standard Normal distribution 148 8.3 Confidence intervals 149 8.4 Statistical tests 150 8.5 Examples of analysis 152 8.6 Regression methods 169 8.7 Other issues 179 8.8 Practice 182 8.9 Technical details 183 9 Trial Size 185 9.1 Introduction 185 9.2 Significance level and power 186 9.3 The fundamental equation 188 9.4 Specific situations 190 9.5 Practical considerations 198 9.6 Further topics 203 9.7 Guideline 206 9.8 Software 206 10 Data and Safety Monitoring 209 10.1 Introduction 209 10.2 The DSMB 211 10.3 Early reviews 214 10.4 Interim reviews 219 10.5 Protocols 228 11 Reporting 229 11.1 Introduction 229 11.2 Publication 230 11.3 Responsibilities 233 11.4 Background 235 11.5 Methods 236 11.6 Findings 248 11.7 When things go wrong 258 11.8 Conclusions 259 11.9 Guidelines 260 Part II Adaptions of the Basic Design 263 12 More Than Two Interventions 265 12.1 Introduction 265 12.2 Unstructured comparisons 266 12.3 Comparisons with placebo (or standard) 270 12.4 Dose-response designs 275 12.5 Factorial trials 280 12.6 Complex structure comparisons 289 13 Paired and Matched Designs 293 13.1 Matched-pair trials 293 13.2 Cross-over trials 305 13.3 Split-mouth designs 311 13.4 Guidelines 317 14 Repeated Measures Design 319 14.1 Introduction 319 14.2 Simplified analysis 322 14.3 Regression models 329 14.4 Auto-correlation 331 14.5 Accounting for auto-correlation 334 14.6 The design effect (DE) 338 14.7 Trial size 344 14.8 Practicalities 347 14.9 Reporting 350 14.10 Matched organs receiving the same intervention 354 15 Non-Inferiority and Equivalence Trials 357 15.1 Introduction 357 15.2 Non-inferiority 358 15.3 Analysis 361 15.4 Trial size 366 15.5 Equivalence 370 15.6 Reporting 373 15.7 Practical Issues 373 15.8 Guidelines 373 16 Cluster Designs 375 16.1 Design features 375 16.2 Procedures 376 16.3 Regression models 379 16.4 Intra-class correlation 380 16.5 Trial size 381 16.6 Analysis 386 16.7 Practicalities 388 16.8 Reporting 388 16.9 Further reading 389 17 Stepped Wedge Designs 391 17.1 Introduction 391 17.2 Notation 392 17.3 Basic structure 396 17.4 Randomisation 398 17.5 Cross-sectional design 398 17.6 Closed cohort design 408 17.7 Practicalities 413 Part III Further Topics 415 18 Genomic Targets 417 18.1 Introduction 417 18.2 Predictive markers 418 18.3 Enrichment design 420 18.4 Biomarker-Stratified Designs 422 18.5 Adaptive threshold designs 431 19 Feasibility and Pilot Studies 435 19.1 Introduction 435 19.2 Feasibility studies 436 19.3 External-pilot studies 437 19.4 Considerations across external-pilot and main trial 444 19.5 Internal-pilot studies 445 19.6 Other preliminary studies 447 19.7 Reporting 449 20 Further Topics 451 20.1 Introduction 451 20.2 Adaptive approaches 452 20.3 Large simple trials 461 20.4 Bayesian methods 463 20.5 Interim analyses 467 20.6 Zelen randomised consent designs 472 20.7 Systematic overviews 476 Statistical Tables 483 Glossary 493 References 503 Index 523
520			_a"It is now more than ten years since the first edition of this book was published. In the intervening years, while many things have remained unchanged, there have also been many new developments over the period. This second edition refreshes the first, refining some of the sections to better explain their contents and, at the same time, replacing some examples with more current illustrations. To reflect the changes, we have created new chapters by splitting and then expanding old chapters. Thus, we now include full chapters on data and safety monitoring including interim analyses of accumulating data, cluster designs, repeated measures, and non-inferiority designs as there has been a rapid increase in the use of such trial designs along with some methodological developments and improvements in statistical software available for analysis. In addition, we have included entirely new chapters on stepped wedge designs, genomic targets and, feasibility and pilot studies. The chapter on stepped wedge designs reflects the growing importance of such complex intervention designs while that on genomic targets highlights the research focus directed towards more individualised medicine. In contrast the new chapter concerned with feasibility and pilot studies brings us back to the early planning stages of the clinical trial which is planned. The chapter is included as there is increasing recognition that perhaps a more structured approach is required at the planning stage of any proposed trial. The intention is to help avoid the conduct of clinical trials which fail due to the basic assumptions made at the planning stage being inappropriate. This edition is divided into three sections: I Basic Considerations, II Adaptions of the Basic Design, and III Further Topics. As the title suggests, the first section is intended to cover topics that are relevant to all randomised trials of whatever design and complexity. Thus, it may be the key section for those who are new to clinical trials and an aide-memoire for those more experienced in this area. For this purpose, it concentrates on the parallel two-group controlled trial with a single outcome measure where patients are randomised individually to one of the two interventions concerned. The second section expands on the individually randomised design in several ways by considering paired designs, repeated assessments of the (same) outcome measure over time, more than two interventions, and non-inferiority trials. It also includes cluster trials, and stepped wedge designs in which groups rather than individuals are randomised to the interventions concerned. The final section deals with genomic targets, feasibility and pilot studies, and a final chapter on miscellaneous topics including adaptive designs, large simple trials and very small trials with new additions describing alpha spending functions and the predictive probability test for use in interim analyses"-- _cProvided by publisher.
545	0		_aAbout the Author David Machin, Leicester Cancer Research Group, University of Leicester, UK; and Medical Statistics Group, School of Health and Related Research, University of Sheffield, UK. Peter M. Fayers, Institute of Applied Health, University of Aberdeen, UK. Bee Choo Tai, Saw Swee Hock School of Public Health, National University of Singapore, and National University Health System, Singapore; and Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.
650		0	_aClinical trials. _0http://id.loc.gov/authorities/subjects/sh85027069.
650		0	_aClinical trials _0http://id.loc.gov/authorities/subjects/sh85027069 _xMethodology. _0http://id.loc.gov/authorities/subjects/sh99001902.
650		0	_aClinical trials _0http://id.loc.gov/authorities/subjects/sh85027069 _xEvaluation. _0http://id.loc.gov/authorities/subjects/sh00005674.
650		0	_aClinical trials _xStatistical methods. _0http://id.loc.gov/authorities/subjects/sh2009120433.
650	1	2	_aRandomized Controlled Trials as Topic _xmethods. _0https://id.nlm.nih.gov/mesh/D016032Q000379.
650	1	2	_aBiomedical Research _xmethods. _0https://id.nlm.nih.gov/mesh/D035843Q000379.
650	2	2	_aResearch Design. _0https://id.nlm.nih.gov/mesh/D012107.
650	2	2	_aData Interpretation, Statistical. _0https://id.nlm.nih.gov/mesh/D003627.
655		4	_aElectronic books.
700	1		_aFayers, Peter M., _0http://id.loc.gov/authorities/names/n97802773 _eauthor.
700	1		_aTai, Bee Choo, _0http://id.loc.gov/authorities/names/n2013183324 _eauthor.
856	4	0	_uhttps://onlinelibrary.wiley.com/doi/book/10.1002/9781119524687 _yFull text is available at Wiley Online Library Click here to view
942			_2ddc _cER