Cochrane Handbook for Systematic Reviews of Interventions by Julian P. T. HigginsCochrane Handbook for Systematic Reviews of Interventions by Julian P. T. Higgins

Cochrane Handbook for Systematic Reviews of Interventions

EditorJulian P. T. Higgins, Sally Green

Hardcover | November 24, 2008

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Healthcare providers, consumers, researchers and policy makers are inundated with unmanageable amounts of information, including evidence from healthcare research. It has become impossible for all to have the time and resources to find, appraise and interpret this evidence and incorporate it into healthcare decisions. Cochrane Reviews respond to this challenge by identifying, appraising and synthesizing research-based evidence and presenting it in a standardized format, published in The Cochrane Library (

The Cochrane Handbook for Systematic Reviews of Interventions contains methodological guidance for the preparation and maintenance of Cochrane intervention reviews. Written in a clear and accessible format, it is the essential manual for all those preparing, maintaining and reading Cochrane reviews. Many of the principles and methods described here are appropriate for systematic reviews applied to other types of research and to systematic reviews of interventions undertaken by others. It is hoped therefore that this book will be invaluable to all those who want to understand the role of systematic reviews, critically appraise published reviews or perform reviews themselves.

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Title:Cochrane Handbook for Systematic Reviews of InterventionsFormat:HardcoverDimensions:672 pages, 9.9 × 6.9 × 1.63 inPublished:November 24, 2008Publisher:WileyLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:0470699515

ISBN - 13:9780470699515

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Table of Contents


Preface xiii

Acknowledgements xv

The Handbook editors xvii

Major contributors xix


1 Introduction 3

Sally Green, Julian PT Higgins, Philip Alderson, Mike Clarke, Cynthia D Mulrow and Andrew D Oxman

1.1 The Cochrane Collaboration 3

1.2 Systematic reviews 6

1.3 About this Handbook 7

1.4 Contributors to the Handbook 8

1.5 Chapter information 9

1.6 References 9

2 Preparing a Cochrane review 11

Edited by Sally Green and Julian PT Higgins

2.1 Rationale for protocols 11

2.2 Format of a Cochrane review 12

2.3 Logistics of doing a review 13

2.4 Publication of Cochrane reviews in print journals and books 24

2.5 Publication of previously published reviews as Cochrane reviews 26

2.6 Declaration of interest and commercial sponsorship 26

2.7 Chapter information 29

2.8 References 29

3 Maintaining reviews: updates, amendments and feedback 31

Julian PT Higgins, Sally Green and Rob JPM Scholten

3.1 Introduction 31

3.2 Some important definitions 32

3.3 Important dates associated with Cochrane reviews 39

3.4 Considerations when updating a Cochrane review 42

3.5 ‘What’s new’ and History tables 46

3.6 Incorporating and addressing feedback in a Cochrane review 48

3.7 Chapter information 48

3.8 References 49

4 Guide to the contents of a Cochrane protocol and review 51

Edited by Julian PT Higgins and Sally Green

4.1 Introduction 52

4.2 Title and review information (or protocol information) 52

4.3 Abstract 55

4.4 Plain language summary 55

4.5 Main text 55

4.6 Tables 70

4.7 Studies and references 72

4.8 Data and analyses 74

4.9 Figures 76

4.10 Sources of support to the review 77

4.11 Feedback 77

4.12 Appendices 78

4.13 Chapter information 78

4.14 References 78


5 Defining the review question and developing criteria for including studies 83

Edited by Denise O’Connor, Sally Green and Julian PT Higgins

5.1 Questions and eligibility criteria 84

5.2 Defining types of participants: which people and populations? 85

5.3 Defining types of interventions: which comparisons to make? 86

5.4 Defining types of outcomes: which outcome measures are most important? 87

5.5 Defining types of study 90

5.6 Defining the scope of a review question (broad versus narrow) 91

5.7 Changing review questions 93

5.8 Chapter information 93

5.9 References 94

6 Searching for studies 95

Carol Lefebvre, Eric Manheimer and Julie Glanville on behalf of the Cochrane Information Retrieval Methods Group

6.1 Introduction 96

6.2 Sources to search 98

6.3 Planning the search process 118

6.4 Designing search strategies 128

6.5 Managing references 142

6.6 Documenting and reporting the search process 144

6.7 Chapter information 146

6.8 References 147

7 Selecting studies and collecting data 151

Edited by Julian PT Higgins and Jonathan J Deeks

7.1 Introduction 151

7.2 Selecting studies 152

7.3 What data to collect 156

7.4 Sources of data 163

7.5 Data collection forms 164

7.6 Extracting data from reports 167

7.7 Extracting study results and converting to the desired format 170

7.8 Managing data 182

7.9 Chapter information 183

7.10 References 183

8 Assessing risk of bias in included studies 187

Edited by Julian PT Higgins and Douglas G Altman on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group

8.1 Introduction 188

8.2 What is bias? 188

8.3 Tools for assessing quality and risk of bias 190

8.4 Introduction to sources of bias in clinical trials 193

8.5 The Cochrane Collaboration’s tool for assessing risk of bias 194

8.6 Presentation of assessments of risk of bias 202

8.7 Summary assessments of risk of bias 202

8.8 Incorporating assessments into analyses 206

8.9 Sequence generation 210

8.10 Allocation sequence concealment 214

8.11 Blinding of participants, personnel and outcome assessors 217

8.12 Incomplete outcome data 219

8.13 Selective outcome reporting 226

8.14 Other potential threats to validity 230

8.15 Chapter information 234

8.16 References 235

9 Analysing data and undertaking meta-analyses 243

Edited by Jonathan J Deeks, Julian PT Higgins and Douglas G Altman on behalf of the Cochrane Statistical Methods Group

9.1 Introduction 244

9.2 Types of data and effect measures 249

9.3 Study designs and identifying the unit of analysis 260

9.4 Summarizing effects across studies 263

9.5 Heterogeneity 276

9.6 Investigating heterogeneity 282

9.7 Sensitivity analyses 289

9.8 Chapter information 292

9.9 References 293

10 Addressing reporting biases 297

Edited by Jonathan AC Sterne, Matthias Egger and David Moher on behalf of the Cochrane Bias Methods Group

10.1 Introduction 298

10.2 Types of reporting biases and the supporting evidence 299

10.3 Avoiding reporting biases 308

10.4 Detecting reporting biases 310

10.5 Chapter information 324

10.6 References 325

11 Presenting results and ‘Summary of findings’ tables 335

Holger J Schünemann, Andrew D Oxman, Julian PT Higgins, Gunn E Vist, Paul Glasziou and Gordon H Guyatt on behalf of the Cochrane Applicability and Recommendations Methods Group and the Cochrane Statistical Methods Group

11.1 Introduction 335

11.2 ‘Characteristics of included studies’ tables 336

11.3 Data and analyses 337

11.4 Figures 341

11.5 ‘Summary of findings’ tables 342

11.6 Additional tables 350

11.7 Presenting results in the text 351

11.8 Writing an abstract 352

11.9 Writing a plain language summary 355

11.10 Chapter information 356

11.11 References 357

12 Interpreting results and drawing conclusions 359

Holger J Schünemann, Andrew D Oxman, Gunn E Vist, Julian PT Higgins, Jonathan J Deeks, Paul Glasziou and Gordon H Guyatt on behalf of the Cochrane Applicability and Recommendations Methods Group

12.1 Introduction 360

12.2 Assessing the quality of a body of evidence 361

12.3 Issues in applicability 367

12.4 Interpreting results of statistical analyses 369

12.5 Interpreting results from dichotomous outcomes (including numbers needed to treat) 372

12.6 Interpreting results from continuous outcomes (including standardized mean differences) 377

12.7 Drawing conclusions 380

12.8 Chapter information 382

12.9 References 383


13 Including non-randomized studies 391

Barnaby C Reeves, Jonathan J Deeks, Julian PT Higgins and George A Wells on behalf of the Cochrane Non-Randomised Studies Methods Group

13.1 Introduction 392

13.2 Developing criteria for including non-randomized studies 396

13.3 Searching for non-randomized studies 404

13.4 Selecting studies and collecting data 407

13.5 Assessing risk of bias in non-randomized studies 412

13.6 Synthesis of data from non-randomized studies 419

13.7 Interpretation and discussion 424

13.8 Chapter information 428

13.9 References 429

14 Adverse effects 433

Yoon K Loke, Deirdre Price and Andrew Herxheimer on behalf of the Cochrane Adverse Effects Methods Group

14.1 Introduction 433

14.2 Scope of a review addressing adverse effects 434

14.3 Choosing which adverse effects to include 437

14.4 Types of studies 438

14.5 Search methods for adverse effects 439

14.6 Assessing risk of bias for adverse effects 442

14.7 Chapter information 445

14.8 References 446

15 Incorporating economics evidence 449

Ian Shemilt, Miranda Mugford, Sarah Byford, Michael Drummond, Eric Eisenstein, Martin Knapp, Jacqueline Mallender, David McDaid, Luke Vale and Damian Walker on behalf of the Campbell and Cochrane Economics Methods Group

15.1 The role and relevance of economics evidence in Cochrane reviews 449

15.2 Planning the economics component of a Cochrane review 454

15.3 Locating studies 459

15.4 Selecting studies and collecting data 462

15.5 Addressing risk of bias 463

15.6 Analysing and presenting results 468

15.7 Addressing reporting biases 472

15.8 Interpreting results 474

15.9 Conclusions 474

15.10 Chapter information 476

15.11 References 476

16 Special topics in statistics 481

Edited by Julian PT Higgins, Jonathan J Deeks and Douglas G Altman on behalf of the Cochrane Statistical Methods Group

16.1 Missing data 482

16.2 Intention-to-treat issues 488

16.3 Cluster-randomized trials 493

16.4 Cross-over trials 498

16.5 Studies with more than two intervention groups 508

16.6 Indirect comparisons and multiple-treatments meta-analysis 513

16.7 Multiplicity and the play of chance 516

16.8 Bayesian and hierarchical approaches to meta-analysis 518

16.9 Rare events (including zero frequencies) 520

16.10 Chapter information 524

16.11 References 524

17 Patient-reported outcomes 531

Donald L Patrick, Gordon H Guyatt and Catherine Acquadro on behalf of the Cochrane Patient Reported Outcomes Methods Group

17.1 What are patient-reported outcomes? 532

17.2 Patient-reported outcomes and Cochrane reviews 533

17.3 Health status and quality of life as PRO outcomes 534

17.4 Issues in the measurement of patient-reported outcomes 537

17.5 Locating and selecting studies with patient-reported outcomes 538

17.6 Assessing and describing patient-reported outcomes 539

17.7 Comparability of different patient-reported outcome measures 540

17.8 Interpreting results 541

17.9 Chapter information 543

17.10 References 544

18 Reviews of individual patient data 547

Lesley A Stewart, Jayne F Tierney and Mike Clarke on behalf of the Cochrane Individual Patient Data Meta-analysis Methods Group

18.1 Introduction 548

18.2 The collaborative nature of IPD meta-analyses 550

18.3 Dealing with data 551

18.4 Analysis 553

18.5 Limitations and caveats 555

18.6 Chapter information 556

18.7 References 557

19 Prospective meta-analysis 559

Davina Ghersi, Jesse Berlin and Lisa Askie on behalf of the Cochrane Prospective Meta-analysis Methods Group

19.1 Introduction 559

19.2 The collaborative nature of prospective meta-analyses 562

19.3 The prospective meta-analysis protocol 563

19.4 Data collection in prospective meta-analysis 566

19.5 Analysis issues in prospective meta-analysis 567

19.6 Chapter information 569

19.7 References 569

20 Qualitative research and Cochrane reviews 571

Jane Noyes, Jennie Popay, Alan Pearson, Karin Hannes and Andrew Booth on behalf of the Cochrane Qualitative Research Methods Group

20.1 Introduction 572

20.2 Incorporating evidence from qualitative research in Cochrane Intervention reviews: concepts and issues

20.3 Qualitative evidence synthesis 576

20.4 Chapter information 583

20.5 References 584

20.6 Further selected reading 587

21 Reviews in public health and health promotion 593

Edited by Rebecca Armstrong, Elizabeth Waters and Jodie Doyle

21.1 Introduction 593

21.2 Study designs to include 594

21.3 Searching 594

21.4 Assessment of study quality and risk of bias 595

21.5 Ethics and inequalities 597

21.6 Context 599

21.7 Sustainability 600

21.8 Applicability and transferability 601

21.9 Chapter information 603

21.10 References 603

22 Overviews of reviews 607

Lorne A Becker and Andrew D Oxman

22.1 Introduction 607

22.2 Preparing a Cochrane Overview of reviews 608

22.3 Format of a Cochrane Overview 613

22.4 Chapter information 631

22.5 References 631

Index 633