Research in the Biomedical Sciences

Transparent and Reproducible

Michael Williams, Michael Curtis, Kevin Mullane

• Publisher: Academic Press
• Year: 2017
• Print ISBN:
  9780128047255
• eBook ISBN:
  9780128047262
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Research in the Biomedical Sciences: Transparent and Reproducible documents the widespread concerns related to reproducibility in biomedical research and provides a best practices guide to effective and transparent hypothesis generation, experimental design, reagent standardization (including validation and authentication), statistical analysis, and data reporting. The book addresses issues in the perceived value of the existing peer review process and calls for the need for improved transparency in data reporting. It reflects new guidelines for publication that include manuscript checklists, replication/reproducibility initiatives, and the potential consequences for the biomedical research community and societal health and well-being if training, mentoring, and funding of new generations of researchers and incentives for publications are not improved. This book offers real world examples, insights, and solutions to provide a thought-provoking and timely resource for all those learning about, or engaged in, performing and supervising research across the biomedical sciences. - Provides a "big picture perspective on the scope of reproducibility issues and covers initiatives that have potential as effective solutions - Offers real-world research context for transparent, reproducible experimental design, execution and reporting of biomedical research with the potential to address aspects of the translational gap in drug discovery - Highlights the importance of reproducibility and the necessary changes in biomedical and pharmaceutical research training and incentives to ensure sustainability

Chapter 1

Reproducibility in Biomedical Research

Kevin Mullane

Michael J. Curtis

Michael Williams

Abstract

The biomedical research ecosystem—academic, federal, and industrial—is dedicated to understanding human disease causality and developing effective therapeutics. The successes of this system over the past century have resulted in many effective drugs leading society to expect an endless supply of new therapeutics, particularly for chronic diseases that lack effective treatments (e.g., Alzheimer’s, diabetes). An increased recognition that the quality, relevance, reliability, and reproducibility of biomedical research cannot be guaranteed despite self-correction and peer review, coupled with the incessant hyping of inconsequential data by authors and their institutions, has led to a situation that is incompatible with sustained success in drug discovery. This risks the loss of credibility with the public, which does not bode well for the future of biomedical research. This chapter outlines the reproducibility problem and its magnitude, setting the stage for potential solutions that are discussed elsewhere in this monograph.

Keywords

reproducibility

fraud

drug discovery

animal models

translational research

Outline

1.1 Introduction

1.2 Defining Reproducibility

1.2.1 A New Lexicon for Reproducibility

1.3 Discipline Specific Terminology in the Biomedical Sciences?

1.4 Experimental Factors in Addition to Statistics That Affect Reproducibility

1.4.1 Unknown Unknowns Affecting Reproducibility

1.4.2 Known Unknowns: Tacit Expertize

1.4.3 Diminishing Effects: Regression to the Mean

1.4.4 Overinterpretation of Effects on Secondary Endpoints in Studies

1.5 The Impact of the Internet on the Evolution of Research Practices—Databases and Third Party Analyses

1.5.1 Data Input

1.5.2 Data Curation

1.5.3 Cross-Database Integration

1.5.4 Analytical Tools

1.6 The Reproducibility Problem

1.6.1 Factors Contributing to the Reproducibility Problem

1.6.2 Human Contributions to the Reproducibility Problem

1.6.3 The Impact of the Internet on Publishing and Disseminating Information

1.7 The Literature on Reproducibility in Biomedical Research

1.7.1 An Age-Old Concern

1.7.2 Concerns in the 21st Century

1.7.3 Reproducibility in the 21st Century: Origins, Scope and Momentum

1.8 Is There a Reproducibility Crisis?

1.9 Trouble at the Laboratory?

1.10 Retractions

1.10.1 RetractionWatch

1.10.2 Continued Citation of Retracted Publications

1.10.3 The Spectrum of Irreproducibility

1.10.4 Research Misconduct

1.10.5 Fraud

1.10.6 Notable Examples of Fraud—Biomedical Researchers Behaving Badly

1.10.7 Fraud as an Opportunity for Reflection and a Learning Moment?

1.11 Reproducibility and Translational Medicine

1.11.1 Animal Models—Predictive Value in Translational Research

1.11.2 Limitations in Animal Models of Human Disease

1.11.3 Issues in Translatability

1.12 Conclusions

1.12.1 A Note on Estimates and Surveys

References

1.1. Introduction

The remarkable progress and benefits scientific research has brought to human well-being are built on a foundation created by previous researchers. The robustness and consequent value of this edifice is predicated on the notion that researchers adhere to sound practices—the responsible conduct of research (NASEM, 2017)—and communicate openly their complete and accurate findings and the methods used to derive them. It is a cumulative process, dependent on both successes and failures, which builds a reliable body to advance scientific knowledge. The process includes the initial discovery, its reproduction by others, and then extension of the initial finding, and where appropriate, correction. Discoveries initially considered as significant or even important might ultimately be tempered or revised as new and improved techniques, tools, and analytical methods are applied that lead to modifications to the initial interpretations. This is a normal part of the research process, and has given rise to the concept that research is vali...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Chapter 1: Reproducibility in Biomedical Research
• Chapter 2: Experimental Planning and Execution
• Chapter 3: Statistical Analysis in Preclinical Biomedical Research
• Chapter 4: Reporting Results
• Chapter 5: Addressing Reproducibility: Peer Review, Impact Factors, Checklists, Guidelines, and Reproducibility Initiatives
• Chapter 6: Biomedical Research in the 21st Century: Multiple Challenges in Resolving Reproducibility Issues
• Index