Evaluating Evidence of Mechanisms in Medicine

1 Introduction.- 1.1 What is a mechanism?.- 1.2 Where does evidence of a mechanism come from?.- 1.3 Why consider evidence of mechanisms?.- 1.3.1 Evaluating efficacy.- 1.3.2 Evaluating external validity.- 1.3.3 Other questions.- 1.3.4 Importance of considering evidence of mechanisms.- 2 How to consider evidence of mechanisms: a summary.- 2.1 Questions to address.- 2.2 Quality level of evidence and status of claim.- 2.3 Identifying evidence of mechanisms in the literature.- 2.4 Evaluating evidence of mechanisms.- 2.5 Using evidence of mechanisms to evaluate causal claims.- 2.6 Overall approach.- 3 Identifying evidence of mechanisms in the literature.- 3.1 Hypothesize a mechanism.- 3.2 Search the literature.- 3.3 Identify the evidence most relevant to the mechanism hypothesis.- 3.4 Presenting the evidence of mechanisms.- 4 Evaluating evidence of mechanisms.- 4.1 Considerations for evaluating evidence of mechanism.- 4.2 Presenting quality of evidence of mechanisms.- 5 Using evidence of mechanisms to evaluate efficacy and external validity.- 5.1 Efficacy.- 5.2 External validity.- 6 Glossary.- 7 References.- 8 Acknowledgements.- 9 Appendix A. A critical appraisal tool for evidence of mechanisms.- 10 Appendix B. GRADE tables with mechanism assessment.- 11 Appendix C: Databases for evidence of mechanisms.- 12 Appendix D: Assessing exposures.- 12.1 Example: carcinogenicity of benzo[a]pyrene.- 12.2 Comparison to IARC.- 12.3 Molecular epidemiology.- 12.4 Comparison to SYRINA.

The authors of this book are members of EBM+ (ebmplus.org), a network of researchers investigating the role of evidence of mechanisms in the health sciences. During the writing of this book, Parkkinen, Wallmann, Wilde and Williamson were based at the Centre for Reasoning, University of Kent; Clarke, Illari and Norell at the Department of Science and Technology Studies, UCL; Kelly at the Department of Public Health and Primary Care, University of Cambridge; Russo at the Department of Philosophy, University of Amsterdam; and Shaw at the National Institute of Health and Care Excellence, UK. This research way supported by the UK Arts and Humanities Research Council and the Leverhulme Trust.